Pathological conditions involving ARTERIES in the skull, such as arteries supplying the CEREBRUM, the CEREBELLUM, the BRAIN STEM, and associated structures. They include atherosclerotic, congenital, traumatic, infectious, inflammatory, and other pathological processes.
The condition of an anatomical structure's being constricted beyond normal dimensions.
Vascular diseases characterized by thickening and hardening of the walls of ARTERIES inside the SKULL. There are three subtypes: (1) atherosclerosis with fatty deposits in the ARTERIAL INTIMA; (2) Monckeberg's sclerosis with calcium deposits in the media and (3) arteriolosclerosis involving the small caliber arteries. Clinical signs include HEADACHE; CONFUSION; transient blindness (AMAUROSIS FUGAX); speech impairment; and HEMIPARESIS.
Pathological conditions of intracranial ARTERIES supplying the CEREBRUM. These diseases often are due to abnormalities or pathological processes in the ANTERIOR CEREBRAL ARTERY; MIDDLE CEREBRAL ARTERY; and POSTERIOR CEREBRAL ARTERY.
A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810)
The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5)
Compounds that bind to and block the stimulation of PURINERGIC P2 RECEPTORS.
The relationship between the dose of an administered drug and the response of the organism to the drug.
The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.
The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.
Drugs that bind to nicotinic cholinergic receptors (RECEPTORS, NICOTINIC) and block the actions of acetylcholine or cholinergic agonists. Nicotinic antagonists block synaptic transmission at autonomic ganglia, the skeletal neuromuscular junction, and at central nervous system nicotinic synapses.
Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders).
Peptide neurotoxins from the marine fish-hunting snails of the genus CONUS. They contain 13 to 29 amino acids which are strongly basic and are highly cross-linked by disulfide bonds. There are three types of conotoxins, omega-, alpha-, and mu-. OMEGA-CONOTOXINS inhibit voltage-activated entry of calcium into the presynaptic membrane and therefore the release of ACETYLCHOLINE. Alpha-conotoxins inhibit the postsynaptic acetylcholine receptor. Mu-conotoxins prevent the generation of muscle action potentials. (From Concise Encyclopedia Biochemistry and Molecular Biology, 3rd ed)
The process which spontaneously arrests the flow of BLOOD from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements (eg. ERYTHROCYTE AGGREGATION), and the process of BLOOD COAGULATION.
An order of nematodes of the subclass ADENOPHOREA. Its organisms commonly have a cylindrical esophagus. The superfamilies of this order are DIOCTOPHYMATOIDEA; MERMITHOIDEA; and TRICHUROIDEA.
The process of the interaction of BLOOD COAGULATION FACTORS that results in an insoluble FIBRIN clot.
Control of bleeding during or after surgery.
A disorder characterized by procoagulant substances entering the general circulation causing a systemic thrombotic process. The activation of the clotting mechanism may arise from any of a number of disorders. A majority of the patients manifest skin lesions, sometimes leading to PURPURA FULMINANS.
Hemorrhagic and thrombotic disorders that occur as a consequence of abnormalities in blood coagulation due to a variety of factors such as COAGULATION PROTEIN DISORDERS; BLOOD PLATELET DISORDERS; BLOOD PROTEIN DISORDERS or nutritional conditions.
Laboratory tests for evaluating the individual's clotting mechanism.
Auditory sensory cells of organ of Corti, usually placed in one row medially to the core of spongy bone (the modiolus). Inner hair cells are in fewer numbers than the OUTER AUDITORY HAIR CELLS, and their STEREOCILIA are approximately twice as thick as those of the outer hair cells.
Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of CONNEXINS, the family of proteins which form the junctions.
The part of the inner ear (LABYRINTH) that is concerned with hearing. It forms the anterior part of the labyrinth, as a snail-like structure that is situated almost horizontally anterior to the VESTIBULAR LABYRINTH.
The narrow passage way that conducts the sound collected by the EAR AURICLE to the TYMPANIC MEMBRANE.
An agent derived from licorice root. It is used for the treatment of digestive tract ulcers, especially in the stomach. Antidiuretic side effects are frequent, but otherwise the drug is low in toxicity.
A purinergic P2X neurotransmitter receptor that plays a role in pain sensation signaling and regulation of inflammatory processes.
An oleanolic acid from GLYCYRRHIZA that has some antiallergic, antibacterial, and antiviral properties. It is used topically for allergic or infectious skin inflammation and orally for its aldosterone effects in electrolyte regulation.
Complex pharmaceutical substances, preparations, or matter derived from organisms usually obtained by biological methods or assay.
The process of finding chemicals for potential therapeutic use.
Concentrated pharmaceutical preparations of plants obtained by removing active constituents with a suitable solvent, which is evaporated away, and adjusting the residue to a prescribed standard.
Plants whose roots, leaves, seeds, bark, or other constituent parts possess therapeutic, tonic, purgative, curative or other pharmacologic attributes, when administered to man or animals.
Use of plants or herbs to treat diseases or to alleviate pain.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Spiny processes on DENDRITES, each of which receives excitatory input from one nerve ending (NERVE ENDINGS). They are commonly found on PURKINJE CELLS and PYRAMIDAL CELLS.
A class of large neuroglial (macroglial) cells in the central nervous system - the largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the BLOOD-BRAIN BARRIER. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with MICROGLIA) respond to injury.
Neoplasms of the brain and spinal cord derived from glial cells which vary from histologically benign forms to highly anaplastic and malignant tumors. Fibrillary astrocytomas are the most common type and may be classified in order of increasing malignancy (grades I through IV). In the first two decades of life, astrocytomas tend to originate in the cerebellar hemispheres; in adults, they most frequently arise in the cerebrum and frequently undergo malignant transformation. (From Devita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2013-7; Holland et al., Cancer Medicine, 3d ed, p1082)
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.
The capacity of the NERVOUS SYSTEM to change its reactivity as the result of successive activations.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
A nucleoside that is composed of ADENINE and D-RIBOSE. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter.
The portion of renal tubule that begins from the enlarged segment of the ascending limb of the LOOP OF HENLE. It reenters the KIDNEY CORTEX and forms the convoluted segments of the distal tubule.
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
A subclass of adenosine A2 receptors found in LEUKOCYTES, the SPLEEN, the THYMUS and a variety of other tissues. It is generally considered to be a receptor for ADENOSINE that couples to the GS, STIMULATORY G-PROTEIN.
A glycoprotein enzyme present in various organs and in many cells. The enzyme catalyzes the hydrolysis of a 5'-ribonucleotide to a ribonucleoside and orthophosphate in the presence of water. It is cation-dependent and exists in a membrane-bound and soluble form. EC
Signal transduction mechanisms whereby calcium mobilization (from outside the cell or from intracellular storage pools) to the cytoplasm is triggered by external stimuli. Calcium signals are often seen to propagate as waves, oscillations, spikes, sparks, or puffs. The calcium acts as an intracellular messenger by activating calcium-responsive proteins.
Act of eliciting a response from a person or organism through physical contact.
All of the divisions of the natural sciences dealing with the various aspects of the phenomena of life and vital processes. The concept includes anatomy and physiology, biochemistry and biophysics, and the biology of animals, plants, and microorganisms. It should be differentiated from BIOLOGY, one of its subdivisions, concerned specifically with the origin and life processes of living organisms.
A publication issued at stated, more or less regular, intervals.
A bibliographic database that includes MEDLINE as its primary subset. It is produced by the National Center for Biotechnology Information (NCBI), part of the NATIONAL LIBRARY OF MEDICINE. PubMed, which is searchable through NLM's Web site, also includes access to additional citations to selected life sciences journals not in MEDLINE, and links to other resources such as the full-text of articles at participating publishers' Web sites, NCBI's molecular biology databases, and PubMed Central.
Lists of persons or organizations, systematically arranged, usually in alphabetic or classed order, giving address, affiliations, etc., for individuals, and giving address, officers, functions, and similar data for organizations. (ALA Glossary of Library and Information Science, 1983)
A musculomembranous sac along the URINARY TRACT. URINE flows from the KIDNEYS into the bladder via the ureters (URETER), and is held there until URINATION.
"The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing.

Effects of heptanol on the neurogenic and myogenic contractions of the guinea-pig vas deferens. (1/619)

1. The effects of the putative gap junction uncoupler, 1-heptanol, on the neurogenic and myogenic contractile responses of guinea-pig vas deferens were studied in vitro. 2. Superfusion of 2.0 mM heptanol for 20-30 min produced the following reversible changes in the biphasic neurogenic contractile response (8 trials): (i) suppression of both phases; (ii) delayed development of both the first as well as the second phase, accompanied by complete temporal separation of the two phases; (iii) prominent oscillations of force during the second (noradrenergic) phase only. 3. To eliminate prejunctional effects of heptanol, myogenic contractions were evoked by field stimulation of the vas in the presence of suramin (200 microM) and prazosin (1 microM). Heptanol (2.0 mM) abolished these contractions reversibly. 4. These results show that (i) heptanol inhibits both excitatory junction potential (EJP)-dependent and non EJP-dependent contractions of the vas; (ii) a postjunctional site of action of heptanol, probably intercellular uncoupling of smooth muscle cells, contributes to the inhibition of contraction.  (+info)

Local regulation of vasopressin and oxytocin secretion by extracellular ATP in the isolated posterior lobe of the rat hypophysis. (2/619)

It is now widely accepted that ATP functions as a signalling substance in the nervous system. The presence of P2 receptors mediating the action of extracellular ATP in brain regions involved in hormonal regulation raises the possibility that a similar role for ATP might also exist in the neuroendocrine system. In this study, the release from the rat isolated neurohypophysis preparation of endogenous ATP, oxytocin and vasopressin (AVP) were measured simultaneously using luciferin-luciferase and RIA techniques. After 70 min preperfusion, electrical field stimulation caused a rapid increase in the amount of ATP in the effluent and the release of AVP and oxytocin also increased stimulation-dependently. Inhibition of voltage-dependent Na+ channels by tetrodotoxin (1 microM) reduced the stimulation-evoked release of AVP and oxytocin; however, the evoked release of ATP remained unaffected. The effect of endogenous ATP on the hormone secretion was tested by suramin (300 microM), the P2 receptor antagonist. Suramin significantly increased the release of AVP, and the release of oxytocin was also enhanced. ATP, when applied to the superfusing medium, decreased the release of AVP, but not that of oxytocin, and its effect was prevented by suramin. ATP (60 nmol), added to the tissues, was readily decomposed to ADP, AMP and adenosine measured by HPLC combined with ultraviolet light detection, and the kinetic parameters of the enzymes responsible for inactivation of ATP (ectoATPase and ecto5'-nucleotidase) were also determined (Km=264+/-2.7 and 334+/-165 microM and vmax=6.7+/-1.1 and 2.54+/-0.24 nmol/min per preparation (n=3) for ectoATPase and ecto5'-nucleotidase respectively). Taken together, our data demonstrate the stimulation-dependent release, P2 receptor-mediated action and extracellular metabolism of endogenous ATP in the posterior lobe of the hypophysis and indicate its role, as a paracrine regulator, in the local control of hormone secretion.  (+info)

Modulation of ATP-responses at recombinant rP2X4 receptors by extracellular pH and zinc. (3/619)

The modulatory effects of extracellular H+ and Zn2+ were tested against ATP-responses at rat P2X4 (rP2X4) receptors expressed in Xenopus oocytes under voltage-clamp conditions. ATP (0.1-100 microM, at pH 7.5), evoked inward currents via rP2X4 receptors (EC50 value, 4.1+/-0.98 microM; nH, 1.2+/-0.1). ATP potency was reduced 2 fold, at pH 6.5, without altering maximal activity. ATP potency was reduced by a further 4 fold, at pH 5.5, and the maximal activity of ATP was also reduced. Alkaline conditions (pH 8.0) had no effect on ATP-responses. Zn2+ (100 nM - 10 microM) potentiated ATP-responses at the rP2X4 receptor by 2 fold, whereas higher concentrations (30 microM - 1 mM) inhibited ATP-responses. Zn2+ potentiation was due to an increase in ATP potency, whereas its inhibitory action was due to a reduction in ATP efficacy. Zn2+ modulation of ATP-responses was pH-dependent. At pH 6.5, the bell-shaped curve for Zn2+ was shifted to the right by 1 log unit. At pH 5.5, Zn2+ potentiation was abolished and its inhibitory effect reduced considerably. Suramin (50 microM) also potentiated ATP-responses at rP2X4 receptors. Neither H+ (pH 6.5 and 5.5), Zn2+ (10-100 microM) or a combination of both failed to reveal an inhibitory action of suramin at rP2X4 receptors. In conclusion, H+ and Zn2+ exerted opposite effects on the rP2X4 receptor by lowering and raising agonist potency, respectively. H+ (> or = 3 microM) and Zn2+ (> or = 30 microM) also reduces agonist efficacy by lowering the number of rP2X4 receptors available for activation. The striking differences between the modulatory actions of H+ and Zn2+ at rP2X4 and rP2X2 receptors are discussed.  (+info)

Effects of vasopressin on the sympathetic contraction of rabbit ear artery during cooling. (4/619)

In order to analyse the effects of arginine-vasopressin on the vascular contraction to sympathetic nerve stimulation during cooling, the isometric response of isolated, 2-mm segments of the rabbit central ear (cutaneous) artery to electrical field stimulation (1-8 Hz) was recorded at 37 and 30 degrees C. Electrical stimulation (37 degrees C) produced frequency-dependent arterial contraction, which was reduced at 30 degrees C and potentiated by vasopressin (10 pM, 100 pM and 1 nM). This potentiation was greater at 30 than at 37 degrees C and was abolished at both temperatures by the antagonist of vasopressin V1 receptors d(CH2)5 Tyr(Me)AVP (100 nM). Desmopressin (1 microM) did not affect the response to electrical stimulation. At 37 degrees C, the vasopressin-induced potentiation was abolished by the purinoceptor antagonist PPADS (30 microM), increased by phentolamine (1 microM) or prazosin (1 microM) and not modified by yohimbine (1 microM), whilst at 30 degrees C, the potentiation was reduced by phentolamine, yohimbine or PPADS, and was not modified by prazosin. The Ca2+-channel blockers, verapamil (10 microM) and NiCl2 (1 mM), abolished the potentiating effects of vasopressin at 37 degrees C whilst verapamil reduced and NiCl2 abolished this potentiation at 30 degrees C. The inhibitor of nitric oxide synthesis, L-NOARG (100 microM), or endothelium removal did not modify the potentiation by vasopressin at 37 and 30 degrees C. Vasopressin also increased the arterial contraction to the alpha2-adrenoceptor agonist BHT-920 (10 microM) and to ATP (2 mM) at 30 and 37 degrees C, but it did not modify the contraction to noradrenaline (1 microM) at either temperature. These results suggest that in cutaneous (ear) arteries, vasopressin potentiaties sympathetic vasoconstriction to a greater extent at 30 than at 37 degrees C by activating vasopressin V1 receptors and Ca2+ channels at both temperatures. At 37 degrees C, the potentiation appears related to activation of the purinoceptor component and, at 30 degrees C, to activation of both purinoceptor and alpha2-adrenoceptor components of the sympathetic response.  (+info)

P2 purinoceptors contribute to ATP-induced inhibition of L-type Ca2+ current in rabbit atrial myocytes. (5/619)

OBJECTIVE: Adenine compounds, including adenosine-5'-triphosphate (ATP) and adenosine (Ado), exert inhibitory effects on myocardium via P1 (subtype A1) purinoceptors. However, ATP per se is a potent activator of P2 purinoceptors. Our aim was to elucidate the respective roles of P1 and P2 purinoceptors in the actions of ATP on L-type calcium current (ICa) in rabbit atrial cells. METHODS AND RESULTS: A whole cell clamp technique was used to record ICa in single atrial cells from the rabbit heart. ATP (0.1 mumol/1-3 mmol/l) produced an inhibitory effect on ICa prestimulated by isoproterenol (ISO, 30 nmol/l), even in the presence of Ado (1 mmol/l). Both 1,3-dipropyl-8-cyclopentylxanthine (A1 blocker) and suramin (P2 blocker) partially blocked the ATP-induced inhibition of ICa, while their co-application nearly completely abolished the effect of ATP. ATP-gamma S (30 mumol/l) inhibited ISO-stimulated ICa significantly, and this inhibition was completely blocked by suramin. alpha, beta-Methylene-ADP, an inhibitor of hydrolysis of AMP to Ado, eliminated the suramin-resistant component of ICa inhibition by ATP. Pretreatment with pertussis toxin (PTX) abolished the ATP inhibition of ICa. Both intracellular dialysis with 8Br cAMP and the application of forskolin plus 3-isobutyl-1-methylxanthine also eliminated the effect of ATP. CONCLUSIONS: Both P1 and P2 purinoceptors are involved in the ATP inhibition of ISO-stimulated ICa in rabbit atrial cells. The P1 stimulation by ATP results from hydrolysis of ATP to Ado. Both the P2- and the P1-mediated effects of ATP and Ado, respectively. involve a PTX-sensitive and cAMP-dependent pathway.  (+info)

P2Z/P2X7 receptor-dependent apoptosis of dendritic cells. (6/619)

Macrophages and thymocytes express P2Z/P2X7 nucleotide receptors that bind extracellular ATP. These receptors play a role in immune development and control of microbial infections, but their presence on dendritic cells has not been reported. We investigated whether extracellular ATP could trigger P2Z/P2X7 receptor-dependent apoptosis of dendritic cells. Apoptosis could be selectively triggered by tetrabasic ATP, since other purine/pyrimidine nucleotides were ineffective, and it was mimicked by the P2Z receptor agonist, benzoylbenzoyl ATP, and blocked by magnesium and the irreversible antagonist, oxidized ATP. RT-PCR analysis confirmed the mRNA expression of the P2Z/P2X7 receptor and the absence of P2X1. Caspase inhibitors and cycloheximide had only a partial effect on the apoptosis, suggesting that a caspase-independent mechanism may also be operative. Brief treatment with ATP led to an increase in the intracellular calcium concentration and permeabilization of the plasma membrane to Lucifer yellow, which diffused throughout the dendritic cell cytosol. Other small extracellular molecules may thus attain a similar intracellular distribution, perhaps activating endogenous proteases that contribute to initiation of apoptosis.  (+info)

Functional and biochemical evidence for heteromeric ATP-gated channels composed of P2X1 and P2X5 subunits. (7/619)

The mammalian P2X receptor gene family encodes two-transmembrane domain nonselective cation channels gated by extracellular ATP. Anatomical localization data obtained by in situ hybridization and immunocytochemistry have shown that neuronal P2X subunits are expressed in specific but overlapping distribution patterns. Therefore, the native ionotropic ATP receptors diversity most likely arises from interactions between different P2X subunits that generate hetero-multimers phenotypically distinct from homomeric channels. Rat P2X1 and P2X5 mRNAs are localized within common subsets of peripheral and central sensory neurons as well as spinal motoneurons. The present study demonstrates a functional association between P2X1 and P2X5 subunits giving rise to hybrid ATP-gated channels endowed with the pharmacology of P2X1 and the kinetics of P2X5. When expressed in Xenopus oocytes, hetero-oligomeric P2X1+5 ATP receptors were characterized by slowly desensitizing currents highly sensitive to the agonist alpha,beta-methylene ATP (EC50 = 1.1 microM) and to the antagonist trinitrophenyl ATP (IC50 = 64 nM), observed with neither P2X1 nor P2X5 alone. Direct physical evidence for P2X1+5 co-assembly was provided by reciprocal subunit-specific co-purifications between epitope-tagged P2X1 and P2X5 subunits transfected in HEK-293A cells.  (+info)

ATP is a mediator of the fast inhibitory junction potential in human jejunal circular smooth muscle. (8/619)

The neurotransmitter(s) that generates the fast component of the inhibitory junction potential (IJP-F) in human jejunal circular smooth muscle is not known. The aim of this study was to determine the role of ATP and purinergic receptors in the generation of the IJP-F in human jejunal circular smooth muscle strips. The P2-receptor antagonist suramin (100 microM) reduced the IJP-F by 28%. Apamin (1 microM) reduced the IJP-F by 25%. Desensitization of muscle strips with the putative P2x-receptor agonist alpha, beta-methylene ATP (alpha,beta-MeATP, 100 microM) decreased the IJP-F by 44%, and desensitization with the putative P2y-receptor agonist adenosine 5'-O-2-thiodiphosphate (ADPbetaS) completely abolished the IJP-F. Desensitization with the putative P2y-receptor agonist 2-methylthioATP had no effect on the IJP-F. Exogenous ATP evoked a hyperpolarization with a time course that matched the IJP-F. The ATP-evoked hyperpolarization was reduced by apamin and suramin, reduced by desensitization with alpha,beta-MeATP (69% decrease), and abolished by desensitization with ADPbetaS. These data suggest that the IJP-F in human jejunal circular smooth muscle is mediated in part by ATP through an ADPbetaS-sensitive P2 receptor.  (+info)

This invention pertains to methods, kits and compositions suitable for the detection, identification and/or quantitation of nucleic acids which are electrostatically immobilized to matrices using non-nucleotide probes which sequence specifically hybridize to one or more target sequences of the nucleic acid but do not otherwise substantially interact with the matrix. Once the nucleic acid is immobilized, the detectable non-nucleotide probe/target sequence complex, formed before or after the immobilization of the nucleic acid, can be detected, identified or quantitated under a wide range of assay conditions as a means to detect, identify or quantitate the target sequence in the sample. Because it is reversibly bound, the non-nucleotide probe/target sequence can optionally be removed from the matrix for detecting, identifying or quantitating the target sequence in the sample. Because the non-nucleotide probe/target sequence is protected against degradation, it is another advantage of this invention that
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AZ11645373 is a highly selective and potent antagonist at human but not rat P2X(7) receptors and will have much practical value in studies of human cells.
AMG-548 hydrochloride, an orally active and selective p38α inhibitor (Ki=0.5 nM), shows slightly selective over p38β (Ki=36 nM) and >1000 fold selective against p38γ and p38δ. AMG-548 hydrochloride is also extremely potent in the inhibition of whole blood LPS stimulated TNFα (IC50=3 nM). AMG-548 hydrochloride inhibits Wnt signaling by directly inhibiting Casein kinase 1 isoforms δ and ε. - Mechanism of Action & Protocol.
This page includes the following topics and synonyms: Platelet ADP Receptor Antagonist, Adenosine Receptor Antagonist, P2Y12 Receptor Antagonist, P2Y Receptor Antagonist, P2Y Receptor Inhibitor, Thienopyridine, Clopidogrel, Plavix, Thiophene, Prasugrel, Effient, Brilinta, Ticagrelor.
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Spacer 9 is a triethylene glycol chain that is 9 atoms long (6 carbons + 3 oxygens), and is used to incorporate a spacer arm into an oligonucleotide. Spacer 9 can be incorporated in consecutive additions whenever a longer spacer is required. Spacer 9 has been used to form non-nucleotide bridges in hairpin loops in oligonucleotides (1), for linking oligonucleotides to epitopes for drug development (2), and for solid-phase immobilization of hybridization probes (3). Multiple incorporation of Spacer 9 has been used to form long, flexible linker arms between the two domains (double-helix forming and triple-helix forming, respectively) of a bifunctional DNA oligonucleotide, in order to maximize the binding flexibility of the two domains for their respective targets (4). This oligo was used to form a peptide nucleic acid (PNA)-DNA conjugate for use in site-directed recombination applications.. References ...
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Antibiotic treatment may fail to protect individuals, if not started early enough, after infection with Bacillus anthracis, due to the continuing activity of toxins that the bacterium produces. Stable and easily stored inhibitors of the edema factor toxin (EF), an adenylyl cyclase, could save lives in the event of an outbreak, due to natural causes or a bioweapon attack. The toxins basic activity is to convert ATP to cAMP, and it is thus in principle a simple phosphatase, which means that many mammalian enzymes, including intracellular adenylcyclases, may have a similar activity. While nucleotide based inhibitors, similar to its natural substrate, ATP, were identified early, these compounds had low activity and specificity for EF. We used a combined structural and computational approach to choose small organic molecules in large, web-based compound libraries that would, based on docking scores, bind to residues within the substrate binding pocket of EF. A family of fluorenone-based inhibitors was
3-Deoxyadenosine-5-Triphosphate lacks a hydroxyl group at the 3 position of the ribose sugar, which prevents elongation of the RNA past the site of incorporation. In the case of mRNA this results in expression of a truncated protein.
Receptor for ATP that acts as a ligand-gated ion channel. This receptor is insensitive to the antagonists PPADS and suramin (By similarity).
Cangrelor, a short-acting, potent and selective small molecule P2Y12 purinoceptor antagonist and platelet ADP receptor antagonist, is being developed by Chiesi
1053-73-2 - WHTCPDAXWFLDIH-KQYNXXCUSA-N - Adenosine 3-phosphate-5-phosphate - Similar structures search, synonyms, formulas, resource links, and other chemical information.
TABLE-US-00006 TABLE 1 Result of calcification and healing Severity of the Calcification Run Cornea Type of calci- occurred Healing no. no. exposure fication (≧1) [%] 1 HH1 medium 1 yes 49.7 1 HH2 phosphate- 0 no 89.8 free 1 HH3 phosphate- 4 yes 22 containing 2 HH7 medium 4 yes 97.8 2 HH8 phosphate- 0 no 100 free 2 HH9 phosphate- 3 yes 92 containing 3 HH13 medium 3 yes n.d. 3 HH16 phosphate- 4 yes n.d. free 3 HH17 phosphate- 0 no 94.8 containing Explanation of the table: 1 n.d.: not determined. 2 The details of the healing in % indicates the size of the healed area relative to the original area of the corneal injury. 3 The strength of the calcification was indicated by means of the value numbers 1 to 5, the assessment taking place with the naked eye and the value numbers standing for the following assessments: 0: no sclerotic phenomena 1: first scleroses are discernible with the naked eye 2: slight sclerosis 3: medium severe sclerosis 4: severe sclerosis 5: complete sclerosis ...
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MetabolismCentral intermediary metabolismSulfur metabolism3(2),5-bisphosphate nucleotidase (TIGR01331; EC; HMM-score: 57.8) ...
Enhanced migration into the cortex induced by P2X receptor blockade during OGD was also suggested by cell spreading observed by DCX immunofluorescence 24 hours after PPADS/OGD treatment (Figure 3A ...
Extracellular ATP is a broad-spectrum cytotoxic agent that produces effects via cell surface P2 purinoceptors. The ligand-gated P2X purinoceptor subtype has very high sequence homology with theRP-2 gene, which encodes for apoptosis. The P2X RNA found in rat vas deferens is expressed preferentially by apoptotic thymocytes. P2X purinoceptor-mediated phasic (twitch) motor responses of the isolated rat vas deferens to neurogenic or exogenous ATP were rapidly, specifically and irreversibly potentiated by bis(2-chloroethyl)sulfide (HD 10-100 μM). Both untreated and HD-potentiated neurogenic responses were Ca++ dependent, blocked in the absence of Ca++ plus 0.1 mM EGTA, by the neuronal Ca++channel blocker ω-conotoxin-MVIIC (3 μM), by the P2 purinoceptor antagonist suramin (100 μM) and by tetrodotoxin (100 nM). HD also potentiated the effects of ATP on isolated guinea pig taenia caecum, where the nucleotide acts at G protein-coupled P2Y purinoceptor subtypes to cause relaxation. HD failed to inhibit ...
In the present study, we demonstrated, for the first time, a functional purinergic neurotransmission between inhibitory motoneurons and human colonic smooth muscle through P2Y1 receptors. Several experimental procedures have been performed to characterize purinergic neurotransmission, including the use of nonselective P2 antagonists such as suramin and PPADS. In this study, we used MRS 2179 as a selective inhibitor of P2Y1 receptors (1, 10). We found that 1) both IJPf and the nonnitrergic relaxation induced by EFS were dose dependently inhibited by MRS 2179, 2) MRS 2179 inhibited the relaxation and hyperpolarization induced by ADPβS (a preferential P2Y agonist), 3) ADPβS reduced the IJP probably by a desensitization mechanism, and 4) P2Y1 receptors were localized in smooth muscle cells as well as in enteric neurons. These results show that ATP or a related purine is released by enteric inhibitory motoneurons, causing a fast hyperpolarization and smooth muscle relaxation. The high sensitivity ...
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2-Naphthylamine-6,8-Disulfonic Acid Monopotassium Salt chemical properties, What are the chemical properties of 2-Naphthylamine-6,8-Disulfonic Acid Monopotassium Salt 842-15-9, What are the physical properties of 2-Naphthylamine-6,8-Disulfonic Acid Monopotassium Salt ect.
Novel agonists and potent antagonists at P2Y_1tn1_1tn1 purinergic receptors: synthesis and biological testing [Elektronische Ressource] = Neue Agonisten und potente Antagonisten an P2Y_1tn1_1tn1-Purinergic-Rezeptoren: Synthese und biologische Untersuchung / vorgelegt von Sophi Damayanti : Novel Agonists and Potent Antagonists at P2Y Purinergic Receptors: 11Synthesis and Biological Testing Neue Agonisten und potente Antagonisten an P2Y Purinergen Rezeptoren: 11 Synthese und Biologische Untersuchung Inaugural-Dissertation zur Erlangung des Doktorgrades der Mathematisch-Naturwissenschaftlichen Fakultät der Heinrich-Heine-Universität Düsseldorf vorgelegt von Sophi
Intradermally administered ATP elicits pain in humans under normal conditions and enhances inflammatory-mediated pain (Bleehen and Keele, 1977; Hamilton et al., 2000) by exciting both mechanoresponsive and mechanoinsensitive C-fibers (Hilliges et al., 2002). Experimentally, the nociceptive effects of intradermally administered P2X receptor agonists [e.g., ATP, α,β-methyleneATP (α,β-meATP), and BzATP; Fig. 1] are short-lasting (1-10 min) and similar in magnitude compared with that produced in the acute phase of the standard formalin test, a neurogenic inflammatory pain model in rodents (Jarvis et al., 2001). As has been observed in humans, both the potency and effectiveness of locally administered P2X receptor agonists to elicit nociceptive responses are increased in situations of peripheral inflammation-induced neuronal sensitization (Hamilton et al., 2000; Sawynok, 2007). Stimulation of spinal P2X receptors may also contribute to nociception as indicated by the ability of i.t. administered ...
In a report reviewing the 37 plenary talks and 80 poster sessions presented at a colloquium on Structure and Function of P2 Purinoceptors held by the American Society for Pharmacology and Experimental Therapeutics in 1995, a historical overview of the field, the molecular biology of P2 purinoceptors, signal transduction pathways of P2 purinoceptors, and a discussion of the physiological and pharma
|p|Contains 1.0 µmole each of 3 nucleotides:|/p| |ul| |li||a href=/2-amino-2-deoxyadenosine-5-triphosphate.html|N-1046 2-Amino-2-deoxyadenosine-5-Triphosphate|/a||/li| |li||a href=/2-amino-2-deoxycytidine-5-triphosphate.html|N-1026 2-Amino-2-d
Name: 3-(3-Methyl-5-oxo-4-,5-dihydropyrazol-1-yl)naphthalene-1,5-disulfonic acid CA Name: Molecular Structure: 3-(3-Methyl-5-oxo-4,5-dihydropyrazol-1-yl)naphthalene-1,5-disulfonic acid,CAS 6338-01-3,384.38,C14H12N2O7S2 3-(3-Methyl-5-oxo-4,5-dihydropyrazol-1-yl)naphthalene-1,5-disulfonic acid,CAS 6338-01-3,384.38,C14H12N2O7S2 Molecular Formula:C14H12N2O7S2 Molecular Weight: 384.38 CAS Registry Number: 6338-01-3
2D-A-Thiol Nucleotide Set K-1001 2-Deoxynucleoside Alpha-Thiol Nucleotide Kit-Contains 1 umole each of 4 nucleotides: -N-8001 2-Deoxyadenosine-5-O-(1-Thiot
AR-C155858 is a potent inhibitor of monocarboxylate transporters MCT1 and MCT2 that binds to an intracellular site involving transmembrane helices 7-10.
undecaprenyl phosphate-α-L-Ara4N: 4-amino-4-deoxy-β-L-arabinosyltransferase (EC; dodecaprenyl phosphate-β-galacturonic acid: lipopolysaccharide core α-galacturonosyl transferase (EC 2.4.1.- ...
undecaprenyl phosphate-α-L-Ara4N: 4-amino-4-deoxy-β-L-arabinosyltransferase (EC; dodecaprenyl phosphate-β-galacturonic acid: lipopolysaccharide core α-galacturonosyl transferase (EC 2.4.1.- ...
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1.MICROBIOLOGICO:  Enterotoxina A  Rubratoxina  Patulina  Fumonisinas b1 y B2 2.ANIMAL: Tetradotoxina Histamina 3.VEGETAL: Ricina
Hi, I have been looking through prior posts to no avail... I am going to do a coomassie staining for the first time, and dont know whether to order brilliant blue G (which contains methanol) or brilliant blue R (which contains ethanol). I do know that the staining and destaining solutions are to contain methanol ...
The activation of different P2Y receptor subtypes reduce T. gondii infection in peritoneal macrophages.Mouse peritoneal macrophages were infected with T. gondii
Shop a large selection of Organonitrogen compounds products and learn more about Brilliant Blue G, pure, ACROS Organics. 5g; Glass bottle.
The structurally related peptides neuropeptide Y (NPY), peptide YY (PYY) and pancreatic polypeptide (PP) are endogenous agonists of the NPY receptor (YR) family, which in humans comprises four functionally expressed subtypes, designated Y1R, Y2R, Y4R and Y5R. Non-peptide antagonists with high affinity and selectivity have been described for the Y1R, Y2R and Y5R, but such compounds are still lacking for the Y4R. In this work, the structures of the high affinity selective (R)-argininamide-type Y1R antagonists BIBP3226 and BIBO3304 were linked via the guanidine or urea moieties to give homo-dimeric argininamides with linker lengths ranging from 31 to 41 atoms. Interestingly, the twin compounds proved to be by far less selective for the Y1R than the R-configured monovalent parent compounds. The decrease in selectivity ratio was most pronounced for Y1R versus Y4R subtype, resulting in comparable affinities of bivalent ligands for Y1R and Y4R (e.g. UR-MK177 ((R,R)-49): Ki = 230 nM (Y1R) and 290 nM ...
TY - JOUR. T1 - CALHM1 ion channel mediates purinergic neurotransmission of sweet, bitter and umami tastes. AU - Taruno, Akiyuki. AU - Vingtdeux, Valérie. AU - Ohmoto, Makoto. AU - Ma, Zhongming. AU - Dvoryanchikov, Gennady. AU - Li, Ang. AU - Adrien, Leslie. AU - Zhao, Haitian. AU - Leung, Sze. AU - Abernethy, Maria. AU - Koppel, Jeremy. AU - Davies, Peter. AU - Civan, Mortimer M.. AU - Chaudhari, Nirupa. AU - Matsumoto, Ichiro. AU - Hellekant, Göran. AU - Tordoff, Michael G.. AU - Marambaud, Philippe. AU - Foskett, J. Kevin. PY - 2013/3/14. Y1 - 2013/3/14. N2 - Recognition of sweet, bitter and umami tastes requires the non-vesicular release from taste bud cells of ATP, which acts as a neurotransmitter to activate afferent neural gustatory pathways. However, how ATP is released to fulfil this function is not fully understood. Here we show that calcium homeostasis modulator 1 (CALHM1), a voltage-gated ion channel, is indispensable for taste-stimuli-evoked ATP release from sweet-, bitter-and ...
We used transcript-specific oligonucleotides to examine the localization in the rat nervous system of the corresponding mRNAs for the two P2X purinoceptor genes cloned recently from the rat vas deferens and PC12 cells. PC12 P2X purinoceptor mRNA was labeled in the olfactory tubercle, striatum, hypothalamus, hippocampus, dentate gyrus, amygdala, cortex, and cerebellum, whereas the vas deferens P2X purinoceptor-specific probes labeled the cerebellum and, at lower levels of expression, the striatum, hippocampus, and cortex. Both types of P2X purinoceptor transcript were found on cell bodies in the nodose and superior cervical ganglia. The presence of these two purinoceptor transcripts in the brain was confirmed by polymerase chain reaction. Two partial cDNAs, identical to sections of the PC12 or vas deferens P2X purinoceptor coding sequences, were amplified from neonatal brain and cerebellum poly(A)+ RNA, respectively. These findings are in broad agreement with earlier Northern blot studies on the ...
Minodronic acid (YM-529) is a third-generation bisphosphonate that directly and indirectly prevents proliferation, induces apoptosis, and inhibits metastasis of various types of cancer cells. Minodronic acid (YM-529) is an antagonist of purinergic P2X2/3 receptors involved in pain. - Mechanism of Action & Protocol.
Fluorescence imaging of extracellular adenosine-5′-triphosphate (ATP) binding sites on inner and outer hair cells isolated from the guinea pig organ of Corti was achieved using the fluorescent analog of ATP, 2′- (or-3′)-O-(trinitrophenyl)adenosine-5′- triphosphate (TNP-ATP; 30-75 microM). This analog, which fluoresces on binding to these sites, was pressure applied by micropipette while hair cells were viewed by fluorescence microscopy. Fluorescence imaging revealed a widespread distribution of extracellular binding sites, including the stereocilia, cuticular plate, and the basolateral margins of the cells, but particularly in infracuticular and infranuclear regions. In support of extracellular binding, simultaneous electrophysiological recordings demonstrated that rapid washout of TNP-ATP-induced fluorescence was dependent upon cell integrity. Suramin, a nonselective P2 purinoceptor antagonist, coapplied with TNP-ATP, reduced the fluorescence observed on the stereocilia and apical ...
P2X purinoceptors, also known as the ATP-gated P2X receptor cation channel family, consist of cation-permeable ligand gated ion channels that open in response to the binding of extracellular ATP.
Comprehensive supplier list for Phosphorothioic acid,O,O-bis(2-ethoxyethyl) S-ethyl ester,Phosphorothioic acid,O,O-bis(2-ethoxyethyl) S-nonyl ester
Chronic hepatitis C: future treatment Astrid Wendt, Xavier Adhoute, Paul Castellani, Valerie Oules, Christelle Ansaldi, Souad Benali, Marc BourlièreDepartment of Hepato-Gastroenterology, Hôpital Saint-Joseph, Marseille, FranceAbstract: The launch of first-generation protease inhibitors (PIs) is a major step forward in HCV treatment. However, the major advance is up to now restricted to genotype 1 (GT-1) patients. The development of second-wave and second-generation PIs yields higher antiviral potency through plurigenotypic activity, more convenient daily administration, fewer side effects and, for the second-generation PIs, potential activity against resistance-associated variants. NS5B inhibitors include nucleoside/nucleotide inhibitors (NIs) and non-nucleotide inhibitors (NNIs). NIs have high efficacy across all genotypes. Sofosbuvir has highly potent antiviral activity across all genotypes in association with pegylated interferon and ribavirin (PR), thus allowing shortened treatment duration. NS5A
Prasugrel cost prasugrel spinal anesthesia prasugrel vs ticagrelor prasugrel bcs class prasugrel chpl prasugrel bleeding reversal prasugrel precio prasugrel ischemic stroke
Ticagrelor (AZD6140) is the first reversibly binding oral P2Y(12) receptor antagonist that blocks ADP-induced platelet aggregation.
Recombinant human RPE protein, fused to His-tag at N-terminus,was expressed in E. coli and purified byusing conventional chromatography techniques.
[105 Pages Report] Check for Discount on Global Ticagrelor Sales Market Report 2017 report by QYResearch Group. In this report, the global Ticagrelor market is valued at...
phacolysin: cpd not in Chemline 7/14/83; RN in 9th CI Form Index for 5,12-dihydroquinoxalino(2,3-b)phenazine-2,9-disulfonic acid (phacolysin in Negwer, 5th ed, #3514; MF=C18H12N4O6S2): 1790-56-3; different structure given for phacolysin in UD 24:43a (C21H17NO6S2) than in Negwer, 5th ed, #3514
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... is classified as a purinergic P2 receptor (P2Y12) antagonist. Other compounds in the same mechanistic class include ... August 2007). "Rapid and reversible modulation of platelet function in man by a novel P2Y(12) ADP-receptor antagonist, INS50589 ... It is characterized as a reversible, competitive receptor antagonist. The IC50 for antagonism of ADP-induced (P2Y12-mediated) ... modifications to dinucleoside polyphosphates and nucleotides that confer antagonist properties at the platelet P2Y12 receptor ...
All of these are antiplatelet agents that block P2Y12 receptors. Data obtained from using P2 receptor-selective antagonists has ... P2 receptors) or adenosine (P1 receptors). P2 receptors have further been divided into five subclasses: P2X, P2Y, P2Z, P2U, and ... IUPHAR GPCR Database - Adenosine receptors IUPHAR GPCR Database - P2Y receptors Purinergic+Receptors at the US National Library ... the first purinergic receptor in plants, DORN1, was discovered. There are three known distinct classes of purinergic receptors ...
... was shown to block P2X3 receptor signaling Burnstock, Geoffrey (June 2006). "Purinergic P2 receptors as targets for novel ... receptor inhibitors. Before the expiry of its patent, the P2Y12 receptor antagonist Clopidogrel (trade name: Plavix) was the ... The purinergic signalling complex of a cell is sometimes referred to as the "purinome". Purinergic receptors, represented by ... Purinergic receptors are specific classes of membrane receptors that mediate various physiological functions such as the ...
Harden TK, Boyer JL, Nicholas RA (1995). „P2-purinergic receptors: subtype-associated signaling responses and structure". ... Role of Prasugrel, a Novel P2Y12 Receptor Antagonist, in the Management of Acute Coronary Syndromes. American Journal of ... Biogeno aminski receptor - Eikozanoidni receptor (Prostaglandinski receptor) - G protein-spregnuti receptor - Imunski receptor ... Neurotransmiterski receptor - Mirisni receptori - Proteazom-aktivirani receptor - Purinski receptor - Transferinski receptor ...
There are various types of purinergic receptors, the most common expressed in the Hensen's cells is the P2 subtype. Another ... Other chemicals such as Calmodulin antagonists W7 and trifluoperazine (TFP) could also induce the gap junctions uncoupling. ... Purinergic receptors have been found in the cells of the Organ of Corti, which are able to mediate physiological and ... and the purinergic receptors that found in the Hensen's cells are all important in providing a suitable electrical and micro ...
GABAA receptor involvement was demonstrated by intrathecal administration of gabazine, a GABAA antagonist, in animals receiving ... Histological staining by another research group examined the distribution of purinergic receptor subtypes throughout the RVM. ... Activation of on cells by ATP was reversed by using the P2 antagonists suramin and pyridoxal-phosphate-6-azophenyl-2′,4′ ... Intra-RVM administration of AP5 or MK-801, NMDA receptor antagonists, resulted in a reversal of the mechanical sensitivity ...
... purinergic P1 receptor - purinergic P2 receptor - purinergic receptor - pyridine - pyrimidine - pyruvate - pyruvate oxidation ... receptor (biochemistry) - receptor antagonist - receptor protein-tyrosine kinase - recombinant fusion protein - recombinant ... interleukin receptor - interleukin-1 receptor - interleukin-2 receptor - interleukin-3 - interleukin-3 receptor - intermediate ... G protein-coupled receptor - G3P - GABA - GABA receptor - GABA-A receptor - gag-onc fusion protein - galanin - gamete - gamma- ...
The adenosine receptors (or P1 receptors) are a class of purinergic G protein-coupled receptors with adenosine as the ... The adenosine receptors are commonly known for their antagonists caffeine and theophylline, whose action on the receptors ... "Towards a revised nomenclature for P1 and P2 receptors". Trends Pharmacol. Sci. 18 (3): 79-82. doi:10.1016/S0165-6147(96)01038- ... Newer adenosine receptor agonists and antagonists are much more potent and subtype-selective, and have allowed extensive ...
... (pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid) is a selective purinergic P2X antagonist. It is able to block ... Lambrecht, G. (1992). "PPADS, a novel functionally selective antagonist of P2 purinoreceptor mediated responses". European ... It appears to be relatively selective for P2X receptors, having no appreciable activity at α1 adrenergic, muscarinic M2 and M3 ... histamine H1, and adenosine A1 receptors. PPADS tetrasodium salt, Santa Cruz Biotechnology Ziganshin, AU (December 1993). " ...
One study in mice showed that blockade of P2X7 receptors attenuates onset of liver fibrosis. Purinergic receptor P2X receptor ... Gartland A, Buckley KA, Hipskind RA, Bowler WB, Gallagher JA (2003). "P2 receptors in bone--modulation of osteoclast formation ... July 2009). "Systemic administration of an antagonist of the ATP-sensitive receptor P2X7 improves recovery after spinal cord ... The P2X7 subunits can form homomeric receptors only with a typical P2X receptor structure. The P2X7 receptor is a ligand-gated ...
... purinergic receptor P2X, ligand-gated ion channel, 1". North RA (2002). "Molecular physiology of P2X receptors". Physiol ... It is possible that the development of selective antagonists for this receptor may provide an effective non-hormonal male ... 2004). "Increased mitogenic and decreased contractile P2 receptors in smooth muscle cells by shear stress in human vessels with ... "A study of P2X1 receptor function in murine megakaryocytes and human platelets reveals synergy with P2Y receptors". Br. J. ...
ADP interacts with a family of ADP receptors found on platelets (P2Y1, P2Y12, and P2X1), which leads to platelet activation.[14 ... P2. (nucleotide). P2X. (ATP). *Agonists: 2-Me-SATP. *α,β-Me-ATP ... Antagonists: 8-Chlorotheophylline. *8-Phenyl-1,3- ... Purinergic signalling. *Pyrophosphates. Hidden categories: *Chemical articles with multiple compound IDs. *Multiple chemicals ... P2Y1 receptors initiate platelet aggregation and shape change as a result of interactions with ADP. ...
Antagonists bind to receptors but do not activate them. This results in a receptor blockade, inhibiting the binding of agonists ... Eicosanoid receptor (Prostaglandin receptor). *Protease-activated receptor. *Neurotransmitter receptor. *Purinergic receptor. * ... GABA receptors: GABA-A, GABA-C. GABA. Cl− , HCO−3 [11]. Glutamate receptors: NMDA receptor, AMPA receptor, and Kainate receptor ... toll-like receptors (TLRs), killer activated and killer inhibitor receptors (KARs and KIRs), complement receptors, Fc receptors ...
Purinergic P2Y Receptor Antagonists. Purinergic P2 Receptor Antagonists. Purinergic Antagonists. Purinergic Agents. ...
Purinergic P2Y Receptor Antagonists. Purinergic P2 Receptor Antagonists. Purinergic Antagonists. Purinergic Agents. ...
Purinergic P2Y Receptor Antagonists. Purinergic P2 Receptor Antagonists. Purinergic Antagonists. Purinergic Agents. ...
Purinergic P2Y Receptor Antagonists. Purinergic P2 Receptor Antagonists. Purinergic Antagonists. Purinergic Agents. ... Any surgery requiring general anesthesia or discontinuation of aspirin and/or an ADP antagonist is planned within 12 months ...
... receptors and will have much practical value in studies of human cells. ... AZ11645373 is a highly selective and potent antagonist at human but not rat P2X(7) ... Purinergic P2 Receptor Antagonists * Quinolinium Compounds * Receptors, Purinergic P2 * Receptors, Purinergic P2X7 ... Characterization of a selective and potent antagonist of human P2X(7) receptors, AZ11645373 Br J Pharmacol. 2006 Dec;149(7):880 ...
Purinergic P2 Receptor Antagonists * Receptors, Purinergic P2 * Receptors, Purinergic P2X4 * pyridoxal phosphate-6-azophenyl-2 ... Here we report that pharmacological blockade of spinal P2X4 receptors (P2X4Rs), a subtype of ionotropic ATP receptor, reversed ... P2X4 receptors induced in spinal microglia gate tactile allodynia after nerve injury Nature. 2003 Aug 14;424(6950):778-83. doi ... Receptors, Purinergic P2 / genetics * Receptors, Purinergic P2 / metabolism* * Receptors, Purinergic P2X4 * Spinal Cord / ...
Regrelor is classified as a purinergic P2 receptor (P2Y12) antagonist. Other compounds in the same mechanistic class include ... August 2007). "Rapid and reversible modulation of platelet function in man by a novel P2Y(12) ADP-receptor antagonist, INS50589 ... It is characterized as a reversible, competitive receptor antagonist. The IC50 for antagonism of ADP-induced (P2Y12-mediated) ... modifications to dinucleoside polyphosphates and nucleotides that confer antagonist properties at the platelet P2Y12 receptor ...
Irreversibly bind to purinergic P2 receptors for ADP GPIIb/IIIa RECEPTOR ANTAGONISTS ABXICIMAB. TIROFIBAN. EPTIFIBATIDE. PGI2. ... Glanzmann Thrombasthenia bleeding disorder Vasoconstriction ADP RECEPTOR ANTAGONISTS CLOPODOGREL TICLODIPINE. PRASUGREL. ... Thromboxane A2 PLATELET AGGREGATION GpIIb-IIIa Receptor Conformation Integrin complex found on platelets. Receptor for ... cAMP in platelet -, GpIIb/IIIa surface receptor inhibition PGI3 (e.g. via Omega-3 fatty acids) = anti-aggregatory t-PA ...
Antagonists of the P2 purinergic receptors P2Y and P2X inhibited these spontaneous potentials, as did the ATP-hydrolyzing ...
... and inflammatory and neuropathic diseases having been linked to the participation of purinergic (P2) receptors, there has been ... Natural products have provided some fascinating new mechanisms and sources to better understand the P2 receptor antagonism. ... that have shown either agonistic or antagonistic effects on P2 receptors. Of those, nine different plant sources demonstrated ... Microorganisms, which represent the largest group, with 26 different sources, showed effects on both receptor subtypes, ranging ...
The ACh effects are diminished in the presence of atropine or M3 muscarinic receptor antagonist and in SCs lacking M3 receptors ... Pharmacological examination showed that the ATP responses are primarily mediated by P2X purinergic receptors. Interestingly, ... Pharmacological examination showed that the ATP responses are primarily mediated by P2X purinergic receptors. Interestingly, ... Previously, we showed that superficially located microvillous cells (MCs) in the MOE expressing transient receptor potential ...
Purinergic P2 Receptor Agonists); 0 (Purinergic P2 Receptor Antagonists); 0 (Receptors, Purinergic P2); 0 (Receptors, ... Agonistas do Receptor Purin rgico P2/farmacologia. Antagonistas do Receptor Purin rgico P2/farmacologia. Ratos Sprague-Dawley. ... 0 (Endothelin Receptor Antagonists); 0 (Endothelin-1); 0 (Receptors, Endothelin); 9NEZ333N27 (Sodium). ... P2) receptors in male rats. Because sex differences in ET-1 and P2 signaling have been reported, we decided to test whether ...
Purinergic Agents. *. Purinergic Antagonists. *. Purinergic P2 Receptor Antagonists. *. Purinergic P2Y Receptor Antagonists ...
1 A-D and Movie S3). However, the P2-purinergic receptor antagonist suramin (100 μM) did not affect the synchronized Ca2+waves ... suggesting that these waves and the interplay between OC cell and NSCs were not dependent on ATP-purinergic receptors. ... egress blocked by gap-junction antagonists (Fig. 2 D-L and 3 D and E and Fig. S4 G-L). Such functional gap junctions can be ...
Depended on Purinergic Type 2 Receptors.. To probe the mechanism of ATP-puffing-induced constriction, 0.5 mM of the P2 receptor ... 2011) The P2 receptor antagonist PPADS supports recovery from experimental stroke in vivo. PLoS One 6:e19983. ... Preconditioning with the P2 receptor antagonist PPADS alleviated pericyte constriction after ischemia, which may be related to ... In the preconditioned ATP puffing study using P2 receptor antagonist PPADS (P178; Sigma-Aldrich), aCSF containing 0.5 mM PPADS ...
PPADS is a nonselective (but nonuniversal) P2 receptor antagonist and does not block P1 receptor (Lambrecht, 2000; Lambrecht et ... The P2 purinergic receptors comprise seven P2X receptor subunits (P2X1-7), which are ligand-gated ion channels (North, 2002), ... Extracellular ATP plays an important role in cellular signaling via P2 type-purinergic receptors (Kanjhan et al., 1996), which ... Furthermore, we found that the protective role of ATP is mediated by the P2 purinergic receptor signaling pathway. Together, ...
Suramin, an anti-parasitic drug and a non-specific P2 purinergic receptor antagonist, has been reported to have neuroprotective ... non-specific P2 antagonist), or suramin analogues (with greater specificity towards selective P2 subtypes), were performed to ... The mechanism involved may be distinct from P2 blockade. View OriginalDownload Slide ... suggesting that suramin promoted regeneration independent of P2 antagonisation. This was also reflected in studies with suramin ...
The first evidence of purinergic signaling was described in 1929, when purines were found to underlie physiological responses ... The effect of P2 receptor antagonists and ATPase inhibition on sympathetic purinergic neurotransmission in the guinea-pig ... Novel P2X7 receptor antagonists ease the pain. Br J Pharmacol. 2007;151(5):565-7.PubMedPubMedCentralCrossRefGoogle Scholar ... Implication for a role of cardiac P2X purinergic receptors. J Pharmacol Exp Ther. 2010;333(3):920-8.PubMedPubMedCentralCrossRef ...
... the secretagogue activity of extracellular ATP by activating a calcium-activated chloride channel via purinergic receptors. ... In vitro, ATP-P2 signaling promotes cystic epithelial cell proliferation, chloride-driven fluid secretion and apoptosis. ... In vitro, ATP-P2 signaling promotes cystic epithelial cell proliferation, chloride-driven fluid secretion and apoptosis. ... Over the last decade, accumulating evidence suggests that the autocrine and paracrine effects of ATP (through its receptor ...
A combination of P2 purinergic and group I/II metabotropic glutamate receptor (mGluR) antagonists reduced the amplitude of the ... D4 Dopamine Receptors Modulate NR2B NMDA Receptors and LTP in Stratum Oriens of Hippocampal CA1. Cerebral Cortex. ISSN 1047- ... The isolated IP3 receptor protein was phosphorylated by both cAMP- and cGMP-dependent protein kinases on two distinct sites as ... Thermolytic phosphopeptide mapping of in situ labeled IP3 receptor by PKA showed labeling on the same sites (Ser-1589 and Ser- ...
Purinergic P2 Receptor Antagonists. Phase 4. 4. Platelet Aggregation Inhibitors. Phase 4. ... fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development. GO:0035607 9.51. FGFR1 FGFR2 ... fibroblast growth factor receptor signaling pathway. GO:0008543 9.76. CBL FGFR1 FGFR2 FGFR3 ... transmembrane receptor protein tyrosine kinase activity. GO:0004714 9.43. FGFR1 FGFR2 FGFR3 ...
Purinergic P2 Receptor Antagonists. Phase 2. 9. Purinergic P2Y Receptor Antagonists. Phase 2. ...
The ATP response was mediated by P2U purinergic receptors based on inhibition by the P2 antagonist suramin and the agonist rank ... G C Churchill, C F Louis; Stimulation of P2U purinergic or alpha 1A adrenergic receptors mobilizes Ca2+ in lens cells.. Invest ... Stimulation of P2U purinergic or alpha 1A adrenergic receptors mobilizes Ca2+ in lens cells. ... Stimulation of P2U purinergic or alpha 1A adrenergic receptors mobilizes Ca2+ in lens cells. ...
Suramin, a P2-purinergic receptor antagonist, did attenuate the Ca2+ response induced by ATP but did not block the propagation ... FGF receptors control alveolar elastogenesis. Rongbo Li, John C. Herriges, Lin Chen, Robert P. Mecham, Xin Sun ... Ilana Berlin and colleagues describe the EGF Receptors activation, endosomal trafficking and eventual downregulation. ...
2e). The P2 receptor antagonist suramin (20 μmol/l) blocked [Ca2+]i responses of pancreatic macrophages to ATP (Fig. 3a), ... We identified functional purinergic receptors in islet macrophages and sought to identify the direct effect of acute purinergic ... a broad P2 receptor antagonist. (b) [Ca2+]i responses of individual macrophages to increasing concentrations of ATP in the ... Islet-resident macrophages express functional purinergic receptors. (a) Traces of [Ca2+]i responses to ATP (100 μmol/l) from ...
The purinergic P2/P4 antagonist di-inosine pentaphosphate or P1-receptor antagonist sulfonylphenyl theophylline, but not the P2 ... receptor antagonist suramin, antagonized the effect of AP4A, suggesting that the observed protection is mediated through an ... and P4-purinergic receptors. AP4A also afforded protection from toxicity induced by unilateral medial forebrain bundle ... GLP-1 receptors are widely expressed in the brain and spinal cord, and our prior studies have shown that Ex-4 is ...
The conjoint increased expression of GFAP and MMP-9 and a purinergic ATP (P2) receptor antagonist reduction in calcium response ... purinergic signaling pathways that are blocked by P2 antagonists. Human, compared to rat, astrocytes had an increased calcium ... This effect was counteracted by GPR17 antagonists and receptor silencing with siRNAs. Finally, uracil nucleotides promoted and ... In this respect, the G protein-coupled membrane receptor GPR17 has recently emerged as a new timer of oligodendrogliogenesis. ...
... subtype-selective P2 antagonists, were added to cardiomyocytes before ischaemic/hypoxic stress; (ii) selected P2 receptors ... Cardiomyocyte death induced by ischaemic/hypoxic stress is differentially affected by distinct purinergic P2 receptors. ... cardiomyocytes; P2 receptors; ischaemic/hypoxic stress; apoptosis. Abstract. Blood levels of extracellular nucleotides (e.g. ... In this study, we aimed at investigating the role of ATP and specific P2 receptors in the appearance of cell injury in a ...
Purinergic receptor antagonists suramin (100 μm), PPADS (20-50 μm), and apyrase (80 U/ml), in contrast, substantially reduced ... Suramin (100 μm) and PPADS (20 and 50 μm), P2 receptor antagonists, both inhibited Ca2+ wave propagation in Müller cells. In 24 ... 2000) Evidence for P2X3, P2X4, P2X5 but not for P2X7 containing purinergic receptors in Müller cells of the rat retina. Mol ... ATP receptor antagonist blocks asymmetric wave propagation. Superfusate flow is from top left to bottom right in all three ...
Purinergic (P2) Receptor Control of Lower Genitourinary Tract Function and New Avenues for Drug Action: An Overview. Current ... Androgen Receptor Antagonists in the Treatment of Prostate Cancer. Clinical Immunology, Endocrine & Metabolic Drugs ( ... A Novel Triazole Nucleoside Suppresses Prostate Cancer Cell Growth by Inhibiting Heat Shock Factor 1 and Androgen Receptor. ...
  • Suramin, an anti-parasitic drug and a non-specific P2 purinergic receptor antagonist, has been reported to have neuroprotective properties. (
  • Intravitreal injection of ciliary neurotrophic factor (CNTF, a potent growth factor for RGC regeneration), PPADS (non-specific P2 antagonist), or suramin analogues (with greater specificity towards selective P2 subtypes), were performed to compare with suramin. (
  • 2). In contrast, PPADS did not enhance GAP-43 expression and axonal regeneration of RGCs above that of control (Fig.3B-C), suggesting that suramin promoted regeneration independent of P2 antagonisation. (
  • Suramin, a P2-purinergic receptor antagonist, did attenuate the Ca2+ response induced by ATP but did not block the propagation of mechanically induced Ca2+ waves. (
  • The purinergic P2/P4 antagonist di-inosine pentaphosphate or P1-receptor antagonist sulfonylphenyl theophylline, but not the P2-receptor antagonist suramin, antagonized the effect of AP4A, suggesting that the observed protection is mediated through an anti-apoptotic mechanism and the activation of P1- and P4-purinergic receptors. (
  • These effects of UTP on bladder neuron excitability were blocked by the P2Y2 receptor antagonist suramin. (
  • Purinergic receptor antagonists suramin (100 μ m ), PPADS (20-50 μ m ), and apyrase (80 U/ml), in contrast, substantially reduced wave propagation into Müller cells (wave radii reduced to 16-61% of control). (
  • IJPf is partially suramin and apamin sensitive, and it is abolished after desensitization with adenosine 5′-β-2-thiodiphosphate (ADPβS) and therefore considered purinergic, possibly through P2 receptors ( 35 ). (
  • The P2Y2-receptor is activated by UTP and ATP and blocked by suramin. (
  • The P2Y4-receptor is not blocked by suramin. (
  • The human P2Y11-receptor is activated by ATP as naturally occurring agonist and it is blocked by suramin and reactive blue 2 (RB2). (
  • Suramin (a P2-purinoceptor antagonist), neomycin (a PLC inhibitor), staurosporin (a PKC inhibitor), and PD98059 (a MEK inhibitor) significantly attenuated the ATP-induced activation of ERK1/2. (
  • BzATP-mediated secretion involved P2Y 2 receptor signaling because it was reduced by the addition of the ATP scavengers apyrase and adenosine deaminase and the P2Y 2 receptor antagonist suramin. (
  • In the jejunum, contraction was abolished or reduced by tetrodotoxin, by atropine, by met-enkephalin, by antagonists to the tachykinin receptors NK1 and NK2 and by the P2-purinoceptor antagonist suramin. (
  • 100 nM), or the purinoceptor antagonists 8- phenyltheophyline (P1 receptors) or suramin (P2 receptors). (
  • Suramin, an ATP antagonist, enhanced the H-effect to 8.6 mV and, like staurosporine, prevented the inhibitory effect of ATP. (
  • Ness e contexto, o objetivo des t e estudo foi identificar novos antagonistas para receptores P2 (P2X7, P2Y2 e P2Y4) e averiguar se eles exercem algum papel n a atenua o da dor e inflama o Na primeira part e dess e trabalho foi identificada a atividade antagonista d o extrato galhos de Joannesia princeps Vell. (
  • In addition, there were seventeen animal sources that affected P2X7 and P2Y1 and P2Y12 receptors. (
  • Mammalian P2X7 receptor pharmacology: comparison of recombinant mouse, rat and human P2X7 receptors. (
  • Dubyak GR. Go it alone no more-P2X7 joins the society of heteromeric ATP-gated receptor channels. (
  • Guo C, Masin M, Qureshi OS, Murrell-Lagnado RD. Evidence for functional P2X4/P2X7 heteromeric receptors. (
  • Recent research has identified a role for microglial P2X receptors in neuropathic pain and inflammatory pain, especially the P2X4 and P2X7 receptors. (
  • Furthermore, by examining parameters such as pH manipulation, the exposure to divalent cations and the P2X7 antagonist Brilliant Blue G, and the use of cells from P2X7 -/- mice, we have shown that the P2X7 receptors are the ATP-activated receptors responsible for the permeabilization phenomenon. (
  • In addition, using Western blot analysis, we have demonstrated the changes in the P2X7 receptor expression in immune cells isolated from different sites in the gut and in the gut-associated lymphoid tissues. (
  • Our findings suggest the existence of the site-specific modulation of P2X7 receptors on epithelial and immune cells, and we define purinergic signaling as a new regulatory element in the control of inflammation and cell fate in the gut and in the gut-associated lymphoid tissues. (
  • The P2X7 receptors are members of the ATP-activated P2X receptor family and constitute a cation ion channel that is permeable to K + , Na + and Ca 2+ . (
  • Depending on the cell type, the activation of the P2X7 receptor by extracellular ATP (ATPe) results in the opening of additional pores that are permeable to hydrophilic solutes with molecular weights below 900 Da including some fluorescent dyes [ 1 ]. (
  • The concentration of ATP that elicits P2X7 receptor activation is estimated to be approximately 1 m M , a level that is rarely achieved under physiological conditions. (
  • In mice, the P2X7 receptors are also activated by physiological concentrations of NAD [ 8 ]. (
  • Under this regard, the P2X7 receptor activated by extracellular ATP possesses a privileged position. (
  • In the regulation of microglial P2X7 by extracellular ATP, microRNAs, among which particularly miR-125b, are lately emerging as key modulators of receptor signaling and functional microglia commitment under basal or amyotrophic lateral sclerosis- (ALS-) evoked inflammatory conditions. (
  • Macrophages from mouse strains with the naturally occurring mutation P451L in the purinergic receptor P2X7 have impaired responses to agonists (1). (
  • Because P2X7 receptors are expressed in bone cells and are implicated in bone physiology, we asked whether strains with the P451L mutation have a different bone phenotype. (
  • By sequencing the most common strains of inbred mice, we found that only a few strains (BALB, NOD, NZW, and 129) were harboring the wild allelic version of the mutation (P451) in the gene for the purinergic receptor P2X7. (
  • The importance of these findings for the interpretation of the earlier reported effects of P2X7 in mice is discussed, along with strategies in developing a murine model for testing the therapeutic effects of P2X7 agonists and antagonists upon postmenopausal osteoporosis. (
  • Prolonged exposure to high agonist concentrations initiates the formation of large pores in the membrane mediated by the P2 subtype P2X7, a feature often assessed by ATP-induced dye uptake [ 7 , 9 ]. (
  • Activation of the P2X7 receptor results in changed cellular morphology and membrane blebbing [ 10 ], which initiates necrotic and apoptotic mechanisms in macrophages [ 11 ]. (
  • There are several studies directing a role to the P2X7 receptor in mediating ATP-induced apoptosis in other cell types [ 7 ] and accordingly increased osteoclast numbers have been found in mice with ablation of the P2X7 receptor (P2X7−/− mice) [ 3 ]. (
  • In humans the single nucleotide polymorphism Glu496Ala is associated with abolished pore formation activity of the P2X7 receptor [ 12 ] and with decreased ATP-induced apoptosis of osteoclasts in vitro [ 13 ]. (
  • In calvarial cells in vitro activation of P2X7 receptors increases expression of osteoblast markers, enhances mineralization, and induces membrane blebbing [ 20 , 21 ]. (
  • The P2X7 receptor is a ligand-gated ion channel belonging to the P2X receptor family. (
  • ATP induced the uptake of ethidium + and Yo-Pro-1 2+ in MEL cells, and this uptake was blocked by the P2X7 antagonist, A-438079. (
  • Moreover, ATP-induced ROS formation was impaired by the P2X7 antagonist, A-438079. (
  • Activation of P2X7 receptors causes isoform-specific translocation of protein kinase C in osteoclasts. (
  • These results support a significant role for the P2X7, P2Y1 and P2Y11 receptors in ATP-induced Ca2+ signalling. (
  • Expression of P2X2 as well as of P2X7 receptors increases in differentiating neurons and glial cells, respectively. (
  • Aschrafi A, Sadtler S, Niculescu C, Rettinger J, Schmalzing G. Trimeric architecture of homomeric P2X2 and heteromeric P2X1 + 2 receptor subtypes. (
  • Cellular distribution and functions of P2 receptor subtypes in different systems. (
  • ATP) are greatly increased during heart ischaemia, but, despite the presence of their specific receptors on cardiomyocytes (both P2X and P2Y subtypes), their effects on the subsequent myocardial damage are still unknown. (
  • Both approaches indicated that the P2Y 2 and P2X 7 receptor subtypes are directly involved in the induction of cell death during ischaemic/hypoxic stress, whereas the P2Y 4 receptor has a protective effect. (
  • This recent knowledge of purinergic receptors' effects on chronic pain provide promise in discovering a drug that specifically targets individual P2 receptor subtypes. (
  • Several subtypes of receptors (P2X 1-7 and P2Y 1, 2, 4, 6, 11-14 ) in each family have been described. (
  • Pharmacological profiles of cloned mammalian P2Y-receptor subtypes. (
  • The expression of a number of P2 receptor subtypes in the gut has been reported. (
  • The use of selective agonists and antagonists of the receptor subtypes P2Y2 and P2Y4 and P2Y6 showed that premature parasite egress may be mediated by the activation of these receptor subtypes. (
  • The P2YR subtypes are typical G protein-coupled receptors (GPCRs), which typically consist of seven transmembrane domains connected by three extracellular and three intracellular loops. (
  • Although pharmacological experiments have suggested the presence of several P2 receptor subtypes on monocytes and lymphocytes, some results are contradictory. (
  • It is now known that both osteoblasts and osteoclasts express multiple P2 receptor subtypes, and the increasing number of nucleotide-induced effects reported to. (
  • Metabotropic receptors, mostly P2Y1 and P2Y2 subtypes, act on embryonic cells or cells at the neural progenitor stage by inducing proliferation as well as by regulation of neural differentiation through NFAT translocation. (
  • The facilitatory effect of UTP on P2X2 sustained currents was mediated by a G protein-coupled P2Y2 receptor/PKC pathway whereas the effect of UTP on P2X3 fast currents was G protein-independent. (
  • These results \ort involvement of P2Y2 receptors in bladder sensation, suggesting an important contribution to bladder neuron excitability and hypersensitivity. (
  • The purinergic receptor P2Y2 receptor mediates chemotaxis of dendritic cells and eosinophils in allergic lung inflammation. (
  • P2Y1-, P2Y2-, P2Y4-, P2Y6-, and P2Y11-receptors all couple to stimulation of phospholipase C. The P2Y11-receptor mediates in addition a stimulation of adenylate cyclase. (
  • The objective of this study was to examine the presence of the P2Y2 receptor and the effects of exogenous ATP on the intracellular mitogen-activated protein kinases (MAPKs) signaling pathway, immediate early genes expression, and cell viability in hESCs. (
  • The current study demonstrated the existence of the P2Y2 purinergic receptor at the mRNA and protein level in hESCs. (
  • Activation of the P2Y2 receptor regulates bone cell function by enhancing ATP release. (
  • Extracellular nucleotides block bone mineralization in vitro: evidence for dual inhibitory mechanisms involving both P2Y2 receptors and pyrophosphate. (
  • The study, next, examined the expression of these receptors and also the P2Y2 receptor during adipogenic differentiation. (
  • 500-fold less effective at inhibiting rat P2X(7) receptor-mediated currents with less than 50% inhibition occurring at 10 microM. (
  • DI-fusion Purinergic receptor inhibition prevents the development of. (
  • Purinergic receptor inhibition prevents the development of smoke-induced lung injury and emphysema. (
  • In contrast, activation of the P2Y12-, P2Y13-, and P2Y14-receptors causes an inhibition of adenylate cyclase activity. (
  • The P2Y12-receptor plays a crucial role in platelet aggregation as well as in inhibition of neuronal cells. (
  • Daily Med: Clopidogrel bisulfate is an inhibitor of ADP-induced platelet aggregation acting by direct inhibition of adenosine diphosphate (ADP) binding to its receptor and of the subsequent ADP-mediated activation of the glycoprotein GPIIb/IIIa complex. (
  • The aftereffect of P2 receptor antago- nists and ATPase inhibition on affectionate purinergic neu- rotransmission in the … Conrad PW, Blight RT, Han J, Milkorn DE, Beitner-Johnson D. Zhou J. Polycystins and primary cilia: primers for corpuscle aeon progression. (
  • Inhibition of gene expression by ATP receptors antagonist suggests that ATP receptors are involved in the ECM biosynthesis in IVD cells. (
  • Moreover, inhibition of gene expression by adenosine receptors antagonists suggests that adenosine receptors are involved in biological activities in the IVD. (
  • Background -ADP plays a key role in hemostasis, acting through 2 platelet receptors: the P2Y 1 receptor and an unidentified P2 receptor, called P2cyc, coupled to adenylyl cyclase inhibition, which is the target of the antiplatelet drug clopidogrel. (
  • Based on the above findings, on pharmacological inhibition by the antagonists oxATP and MRS2179, and on the absence of α,βmeATP-induced inward current in whole-cell recording, P2X 7 and P2Y 1 were identified as the main ionotropic and metabotropic P2 receptors active in OPs. (
  • Effect of nicotine and nicotinic receptor agonists on latent inhibition in the rat. (
  • AZ11645373 up to 10 microM, had no agonist or antagonist actions on membrane currents due to P2X receptor activation at human P2X(1), rat P2X(2), human P2X(3), rat P2X(2/3), human P2X(4), or human P2X(5) receptors expressed in HEK cells. (
  • We found that infusion of AT R agonist C21 in obese Zucker rats (OZR) increased urine flow and urinary Na excretion which were attenuated by simultaneous infusion of the AT R antagonist PD123319 or the MasR antagonist A-779. (
  • It was found that with treatment of the purinergic ligand 2-methylthioladenosine 5' diphosphate (2-MeSADP), which is an agonist and has a high preference for the purinergic receptor type 1 isoform (P2Y1R), significantly contributes to the reduction of an ischemic lesions caused by cytotoxic edema. (
  • The human P2Y4-receptor has a strong preference for UTP as agonist, whereas the rat P2Y4-receptor is activated about equally by UTP and ATP. (
  • The receptor prefers UDP as agonist and is selectively blocked by 1,2-di-(4-isothiocyanatophenyl)ethane (MRS2567). (
  • Finally, UDP has been reported to act on receptors for cysteinyl leukotrienes as an additional agonist--indicating a dual agonist specificity of these receptors. (
  • Similarly, Ca 2+ transients evoked by the P2Y 1 receptor subtype-specific agonist 2-(Methylthio)adenosine 5'-diphosphate were also blocked by MRS2179. (
  • 2) refining the profile by the use of antagonists, 3) testing for desensitization of the response to agonist and 4) determining the presence of transcripts for pyridine-sensitive P2Y receptors. (
  • Loss of sensory function after nerve injury results in spontaneous firing of dorsal horn neurons in spinal cord a selective GalR1 receptor agonist may constitute a valuable tool for the treatment of neuropathic and inflammatory pain. (
  • Furthermore, we found that the protective role of ATP is mediated by the P2 purinergic receptor signaling pathway. (
  • The Pannexin-1 channel (PANX1) is an integral component of the P2X/P2Y purinergic signaling pathway and the key contributor to pathophysiological ATP release. (
  • Here we report that pharmacological blockade of spinal P2X4 receptors (P2X4Rs), a subtype of ionotropic ATP receptor, reversed tactile allodynia caused by peripheral nerve injury without affecting acute pain behaviours in naive animals. (
  • Pharmacological examination showed that the ATP responses are primarily mediated by P2X purinergic receptors. (
  • P2Y 1 receptors can be an important pharmacological target to modulate smooth muscle excitability. (
  • All these results are consistent, but they are indirect evidence due to the lack of specific pharmacological tools to demonstrate a purinergic pathway through a specific receptor. (
  • DI-fusion Pharmacological characterization of the human P2Y11 receptor. (
  • The P2XR family consists of 7 different receptor subunits (P2X1-7), which are encoded by different genes and able to form homomeric and heteromeric functional channels with distinct pharmacological and biophysical properties. (
  • Although preliminary, these results indicate that purinergic receptors are putative pharmacological targets that should be further explored in future studies. (
  • Natural products have provided some fascinating new mechanisms and sources to better understand the P2 receptor antagonism. (
  • The effect of medullary NaCl loading on Na excretion was determined in intact and ovariectomized (OVX) female Sprague-Dawley rats with and without ET-1 or P2 receptor antagonism. (
  • The ATP-evoked Ca 2+ transients were present under the blockade of neuronal activity, but were inhibited by Ca 2+ store depletion and antagonism of the G protein coupled purinergic P2Y 1 receptor subtype-specific antagonist MRS2179. (
  • In addition, the antagonism of P2 receptors was able to evoke a significant decrease in the arterial pressure, heart rate and splanchnic nerve activity in SHR, but not in Wistar rats. (
  • Adrenergic receptor antagonism induces neuroprotection and facilitates recovery from acute ischemic stroke. (
  • Antagonism at the CCK receptor by YM022 has been shown to produce analgesia following constriction injury to rat sciatic nerve. (
  • More specifically, the epinephrine response was mediated by the alpha 1A adrenergic receptor subtype based on the greater potencies exhibited by the alpha 1A subtype selective competitive antagonists WB 4101 and 5-methylurapidil compared to the alpha 1B and alpha 1D selective antagonists spiperone and BMY 7378, respectively. (
  • We conclude that xenin exerts excitatory effects on a neuronal subtype receptor in the jejunum, with participation of muscarinic, purinergic and tachykinin-related mechanisms. (
  • Xenin exerts relaxing effects on the colon by interaction with a myokinetic subtype receptor involving Ca(++)-dependent K+ channels and the P2-purinoceptor. (
  • Few physiological functions have been firmly established to a specific receptor subtype, partly because of a lack of truly selective agonists and antagonists. (
  • Here, we provide genetic evidence that activity-induced calcium accumulation in neonatal TPSCs is mediated exclusively by one subtype of metabotropic purinergic receptor. (
  • The present study was conducted to determine the subtype of the functional purinergic receptor in gerbil stria vascularis, to test if receptor activation leads to elevation of intracellular [Ca 2+ ] and to test if the response to these receptors undergoes desensitization. (
  • Recent studies indicate that spinal melanocortin receptors (the MC4 subtype) are upregulated in animal models of neuropathic pain . (
  • This involvement suggests the possible use of purinergic agonists and antagonists as therapeutic targets for ocular inflammation. (
  • The term purinergic receptor was originally introduced to illustrate specific classes of membrane receptors that mediate relaxation of gut smooth muscle as a response to the release of ATP (P2 receptors) or adenosine (P1 receptors). (
  • P2X receptors mediate a large variety of responses including fast transmission at central synapses, contraction of smooth muscle cells, platelet aggregation, macrophage activation, and apoptosis. (
  • Membrane-bound P2-receptors mediate the actions of extracellular nucleotides in cell-to-cell signalling. (
  • Furthermore, extracellular ATP per se is toxic for primary neuronal dissociated and organotypic CNS cultures from cortex, striatum and cerebellum and P2 receptors can mediate and aggravate hypoxic signaling in many CNS neurons. (
  • ATP is an extracellular signaling molecule that activates specific G protein-coupled P2Y receptors in most cell types to mediate diversely biological effects. (
  • Purinergic receptors are specific classes of membrane receptors that mediate various physiological functions such as the relaxation of gut smooth muscle, as a response to the release of ATP or adenosine. (
  • The concept that adenosine triphosphate (ATP) can act as an extracellular signaling molecule via interactions with specific purinergic receptors to mediate a wide variety of processes as diverse as neurotransmission (Edwards et al. (
  • One relevant area of investigation is the group of ionotropic (P2X) and metabotropic (P2Y) receptors, which have been found in all studied cells so far. (
  • De Roo M, Rodeau JL, Schlichter R. Dehydroepiandrosterone potentiates native ionotropic ATP receptors containing the P2X2 subunit in rat sensory neurones. (
  • To distinguish P2 receptors further, the subclasses have been divided into families of metabotropic (P2Y, P2U, and P2T) and ionotropic receptors (P2X and P2Z). (
  • These ligand-gated ion channels are nonselective cation channels responsible for mediating excitatory postsynaptic responses, similar to nicotinic and ionotropic glutamate receptors. (
  • ATP and UTP), released during bladder distension or from damaged cells after tissue insult, are thought to play an important role in bladder physiological and pathological states by actions at ionotropic P2X and metabotropic P2Y receptors. (
  • Both ionotropic P2X and metabotropic P2Y receptors can be activated by extracellular ATP ( Ralevic and Burnstock, 1998 ), suggesting that P2Y receptors may also contribute to altered sensations in PBS/IC. (
  • Extracellular nucleotides (ATP, ADP, UTP and UDP) exert a wide range of biological effects in blood cells mediated by multiple ionotropic P2X receptors and G protein-coupled P2Y receptors. (
  • Moreover, there are no examples of P2X2 receptor mediated fast ATP synaptic transmission in the brain. (
  • 1. Bo X, Alavi A, Xiang Z, Oglesby I, Ford A, Burnstock G. (1999) Localization of ATP-gated P2X2 and P2X3 receptor immunoreactive nerves in rat taste buds. (
  • Anti-NGF treatment could also increase the residual current typical of heteromeric P2X2/3 receptors, consistent with enhanced membrane location of P2X2 subunits. (
  • The release of gamma-aminobutyric acid (GABA) and ATP from rat beta cells was monitored using an electrophysiological assay based on overexpression GABA(A) or P2X2 receptor ion channels. (
  • Heterogeneity of P2X receptors in sympathetic neurons: contribution of neuronal P2X1 receptors revealed using knockout mice. (
  • We also found that exogenous ATP protected Aβ42-mediated reduction in synaptic molecules, such as NMDA receptor 2A and PSD-95, through P2 purinergic receptors and prevented Aβ42-induced spine reduction in cultured primary hippocampal neurons. (
  • These receptors are greatly distributed in neurons and glial cells throughout the central and peripheral nervous systems. (
  • Moreover, these receptors have been implicated in integrating functional activity between neurons, glial, and vascular cells in the central nervous system, thereby mediating the effects of neural activity during development, neurodegeneration, inflammation, and cancer. (
  • In the present study, we examined the ability of P2Y receptors to sensitize and modulate P2X mediated-responses in mouse bladder sensory neurons. (
  • We also examined P2X and P2Y receptor expression in bladder neurons. (
  • and 6 ) P2Y 1 receptors were localized in smooth muscle cells as well as in enteric neurons. (
  • Although NGF block is proposed as a novel analgesic approach, its consequences on nociceptive purinergic P2X receptors of trigeminal ganglion neurons remain unknown. (
  • We investigated whether neutralizing NGF might change the function of P2X3 receptors natively coexpressed with NGF receptors on cultured mouse trigeminal neurons. (
  • A comparison of the effects of valproate and its major active metabolite E-2-en-valproate on single unit activity of substantia nigra pars reticulata neurons in rats. (
  • Following axotomy the expression of GalRz receptor mRNA is reduced, while recent evidence suggests that the GaIR1 receptor is upregulated in dorsal horn neurons following nerve injury, as well as during inflammation (Figure I-20). (
  • Modulation of arterial pressure by P2 purinoceptor. (
  • We recently reported that natriuresis produced by renal medullary salt loading is dependent on endothelin (ET)-1 and purinergic (P2) receptors in male rats. (
  • ET or P2 receptor blockade did not attenuate the natriuretic effect of medullary NaCl loading in intact females, whereas ET or P2 receptor blockade attenuated the natriuretic response to NaCl loading in OVX rats. (
  • Activation of medullary P2Y and P2Y receptors by UTP infusion had no significant effect in intact females but enhanced Na excretion in OVX rats. (
  • Combined ET receptor blockade significantly inhibited the natriuretic response to UTP observed in OVX rats. (
  • In light of some reports suggesting a potential positive interaction between these receptors, we tested hypothesis that renal AT R and MasR physically interact and are interdependent to stimulate cell signaling and promote natriuresis in obese rats. (
  • New Findings What is the central question of this study?Is purinergic signalling in the pial vessels involved in the control of vascular tone in the ventral surface of the brainstem, affecting high blood pressure and sympathetic overactivity in spontaneously hypertensive rats? (
  • The application of an antagonist of P2 receptors, pyridoxalphosphate-6-azophenyl-2 `,4 `-disulfonic acid (10 mu m), or of P2Y1a receptors, MRS2179 (100 mu m), on the surface of RVLM pial vessels of SHR produced an increase in the diameter of blood vessels (PPADS: 31 +/- 1.4 mu m or MRS2179: 32 +/- 0.78 mu m vs. saline: 27 +/- 1.2 mu m), an effect not observed in normotensive Wistar rats. (
  • Our data show that SHR have higher vascular tone of pial vessels in the RVLM region when compared to the normotensive Wistar rats, a mechanism that relies on purinergic signalling through P2 receptors, suggesting a possible association with higher activity of sympathoexcitatory neurones, and sustained increases in blood pressure. (
  • The MC4 melanocortin receptor agonists MTII and d-Tyr-MTII increase the sensitivity of rats to painful stimuli following sciatic nerve constriction. (
  • The subject invention relates to novel P2X3 receptor antagonists that play a critical role in treating disease states associated with pain, in particular peripheral pain, inflammatory pain, or tissue injury pain that can be treated using a P2X3 receptor subunit modulator. (
  • Treatment with an NGF antibody (24 h) decreased P2X3 receptor-mediated currents and Ca2+ transients, an effect opposite to exogenously applied NGF. (
  • Despite anti-NGF treatment, CGRP could still enhance P2X3 receptor activity, indicating separate NGF- or CGRP-mediated mechanisms to upregulate P2X3 receptors. (
  • In an in vivo model of mouse trigeminal pain, anti-NGF pretreatment suppressed responses evoked by P2X3 receptor activation. (
  • Inhibitors of purinergic receptors include clopidogrel, prasugrel and ticlopidine, as well as ticagrelor. (
  • AR-C69931MX), the nucleoside analogue AZD6140, as well as active metabolites of the thienopyridine compounds clopidogrel and prasugrel block the receptor. (
  • Pharmacodynamics, pharmacokinetics, and safety of the oral reversible P2Y12 antagonist AZD6140 with aspirin in patients with atherosclerosis: a double-blind comparison to clopidogrel with aspirin. (
  • Clopidogrel (Plavix), a P2Y12 receptor antagonist, inhibits bone cell function in vitro and decreases trabecular bone in vivo. (
  • 2006). „The active metabolite of Clopidogrel disrupts P2Y12 receptor oligomers and partitions them out of lipid rafts" . (
  • The most interesting findings were the high mRNA expression of P2Y 12 receptors in lymphocytes potentially explaining the anti-inflammatory effects of clopidogrel, P2Y 13 receptors in monocytes and a previously unrecognised expression of P2X 4 in lymphocytes and monocytes. (
  • Residual platelet ADP reactivity after clopidogrel treatment is dependent on activation of both the unblocked P2Y(1) and the P2Y (12) receptor and is correlated with protein expression of P2Y (12). (
  • P2Y4-receptors are expressed in the placenta and in epithelia. (
  • Molecular cloning and characterization of the mouse P2Y4 nucleotide receptor. (
  • Mouse P2Y4 Nucleotide Receptor Is a Negative Regulator of Cardiac Adipose-Derived Stem Cell Differentiation and Cardiac Fat Formation. (
  • The expression of P2Y1-receptors is widespread. (
  • Stimulation of P2U purinergic or alpha 1A adrenergic receptors mobilizes Ca2+ in lens cells. (
  • While mechanical stimulation has shown to promote ECM biosynthesis and ATP release, the effects of direct stimulation of the purinergic pathway by extracellular ATP and its derivative, adenosine, on the ECM biosynthesis in IVD cells have not been elucidated. (
  • The purpose of this study is to test the hypothesis that the stimulation of VSMC P2XR receptors (P2XRs) contributes to ATP-evoked sustained vasoconstrictions in rat middle cerebral arteries (RMCAs). (
  • the expression of these proteins decreased when additional inhibitors of the TGF-ß receptor were added. (
  • We specialize in small molecule inhibitors, agonists, antagonists and screening libraries! (
  • It is believed that ATP functions as a pronociceptive neurotransmitter, acting at specific P2X and P2Y receptors in a systemized manner, which ultimately (as a response to noxious stimuli) serve to initiate and sustain heightened states of neuronal excitability. (
  • The P2Y13-receptor is expressed in immunocytes and neuronal cells and is again activated by ADP and 2-methylthio-ADP. (
  • Conversely, several P2 receptor antagonists abolish the cell death fate of primary neuronal cultures exposed to excessive glutamate, serum / potassium deprivation, hypoglycemia and chemical hypoxia. (
  • Gene expression silencing assays indicate that these receptors are important for the progress of differentiation and neuronal or glial fate determination. (
  • The enteric nervous system of P2Y13 receptor null mice is resistant against high-fat-diet- and palmitic-acid-induced neuronal loss. (
  • AZ11645373 inhibited human P2X(7) receptor responses in HEK cells in a non-surmountable manner with K (B) values ranging from 5 - 20 nM, with mean values not significantly different between assays. (
  • Previously, we showed that superficially located microvillous cells (MCs) in the MOE expressing transient receptor potential channel M5 (TRPM5) are cholinergic and chemoresponsive and that they play an important role in maintaining odor responses and olfactory-guided behavior under challenging chemical environment. (
  • The first evidence of purinergic signaling was described in 1929, when purines were found to underlie physiological responses in the circulatory and digestive system. (
  • Background and Purpose- Current knowledge states that vasoconstrictor responses to ATP are mediated by rapidly desensitizing ligand-gated P2X1 receptors in vascular smooth muscle cells (VSMCs). (
  • 1 ATP evokes contractile responses by activation of nonselective ligand-gated cation channels, P2X receptors (P2XR), expressed in the plasma membrane of vascular smooth muscle cells (VSMCs). (
  • Immune cells express various P2Rs, and purinergic signaling mechanisms have been shown to play key roles in the regulation of many aspects of immune responses. (
  • 12 At the intracellular level, ADP has been shown to act synergistically with thrombin to activate PI 3-kinase 13 and phospholipase D. 14 Two ADP receptors involved in ADP-induced platelet responses have been described to date. (
  • Contractile responses of the sphincter to EFS were unaffected by the muscarinic receptor antagonist atropine (1 µM), but were almost completely abolished by the adrenergic neuron blocker guanethidine (10 µM). (
  • The cyclic pyridoxine-alpha4, 5-monophosphate, compound 2 (MRS 2219), was found to be a selective potentiator of ATP-evoked responses at rat P2X1 receptors with an EC50 value of 5.9 +/- 1.8 microM, while the corresponding 6-azophenyl-2',5'-disulfonate derivative, compound 3 (MRS 2220), was a selective antagonist. (
  • In contrast, the pain responses are attenuated following pretreatment with the melanocortin receptor antagonist SHU9119 [34]. (
  • PEA is a lipidergic messenger and is known to mimic several endocannabinoid-induced biological responses via novel mechanism of action, without binding to CB1, CB2, and abn-CBD receptors. (
  • Cangrelor is a selective, reversible, P2Y12 platelet receptor antagonist which inhibits ADP platelet aggregation. (
  • Because ATP is co-released with insulin and is exclusively secreted by beta cells, the activation of purinergic receptors on resident macrophages facilitates their awareness of beta cell secretory activity. (
  • It involves the activation of purinergic receptors in the cell and/or in nearby cells, thereby regulating cellular functions. (
  • In summary, adenosine and nucleotides can activate receptors in ocular structures susceptible to suffer from inflammatory processes. (
  • Purinergic signalling (or signaling: see American and British English differences) is a form of extracellular signalling mediated by purine nucleotides and nucleosides such as adenosine and ATP. (
  • Released nucleotides can be hydrolyzed extracellularly by a variety of cell surface-located enzymes referred to as ectonucleotidases that control purinergic signalling. (
  • Bone cells express several types of P2 receptors [ 6 ], allowing them to respond differently to nucleotides, depending on the types of nucleotides present, their concentration, and the duration of exposure [ 7 , 8 ]. (
  • Nucleotides and nucleosides act as potent extracellular messengers via the activation of the family of cell-surface receptors termed purinergic receptors. (
  • Accumulating evidence indicates that extracellular nucleotides, signaling through P2 receptors, play a significant role in bone remodeling. (
  • Receptor activation by uracil nucleotides (P2Y 2 , P2Y 4 or P2Y 6 ) leads to a decrease in the electrogenic K + secretion. (
  • At the time of the original investigations, the purinergic receptor field recognized only 1 receptor responding to uracil nucleotides (P2U, now P2Y 2 receptor). (
  • In addition to P2Y 2 , both the P2Y 4 and P2Y 6 receptors also respond to uracil nucleotides. (
  • We measured membrane currents, calcium influx, and YOPRO-1 uptake from HEK cells expressing individual P2X receptors, and YOPRO1 uptake and interleukin-1beta release from THP-1 cells in response to ATP and the ATP analogue benzoylbenzoyl ATP (BzATP). (
  • Purinergic receptors, also known as purinoceptors, are a family of plasma membrane molecules that are found in almost all mammalian tissues. (
  • The immune cells express purinergic P2 receptors in their membrane--subdivided into P2Y and P2X subfamilies--whose activation is important for infection control. (
  • Activated platelets participate in thrombin generation through exposure of membrane receptors for blood coagulation proteins, through release of coagulation factors stored in their α-granules, 1 and through formation of a procoagulant surface by rearrangement of their membrane phospholipids to expose negatively charged phosphatidylserine. (
  • It was previously shown that K + secretion by strial marginal cell epithelium is under the control of G-protein coupled receptors of the P2Y family in the apical membrane. (
  • The results support the conclusion that regulation of K + secretion across strial marginal cell epithelium occurs by P2Y 4 receptors at the apical membrane. (
  • We have recently identified a novel set of cyclic imide compounds that inhibited P2X(7) receptor-mediated dye uptake in human macrophage THP-1 cells. (
  • Thirty-four different sources of these compounds have been found so far, that have shown either agonistic or antagonistic effects on P2 receptors. (
  • While some P2 receptor-selective compounds have proven useful in preclinical trials, more research is required to understand the potential viability of P2 receptor antagonists for pain. (
  • 8 These compounds were recently shown to significantly inhibit the in vitro thrombin generation triggered by low concentrations of tissue factor in the presence of platelets by inhibiting platelet ADP receptors. (
  • Structure-activity relationships for SNC80 and related compounds at cloned human delta and mu opioid receptors. (
  • In addition, we describe for the first time the expression of P2 receptors in CD34 + stem and progenitor cells implicating a potential role of P2 receptors in hematopoietic lineage and progenitor/stem cell function. (
  • In particular, we will focus on the expression of P2 receptors by osteoclasts and, more specifically, the P2X(7) receptor and its paradoxical role in osteodast function. (
  • Furthermore, dysfunction of the polycystin signal transduction pathways promotes the secretagogue activity of extracellular ATP by activating a calcium-activated chloride channel via purinergic receptors. (
  • Gonzales, Silvia D., "The Effects of ATP and Adenosine on the Extracellular Matrix Biosynthesis Via Purinergic Pathways" (2014). (
  • Other proposed mechanisms contributing to this hemostatic imbalance include decreased platelet production, increased platelet destruction from hypersplenism, decreased synthesis of Vitamin K-dependent and independent clotting factors and anticoagulant factors, and alterations in purinergic signaling pathways. (
  • The studies presented in this thesis, using human dental pulp-derived MSCs (hDP-MSCs), aimed to investigate ATP-induced purinergic Ca2+ signalling and Ca2+-dependent signalling pathways in regulating cell migration and adipogenic differentiation and examine the hypothesis that the mechanically activated Ca2+-permeable Piezo1 channel regulates hDP-MSC migration via ATP release and activation of the P2 receptors. (
  • In summary, the studies presented in this thesis gain a better understanding of ATP-induced Ca2+ downstream signalling pathways in the regulation of MSC migration and adipogenic differentiation, and also provide evidence to support an important role for the Piezo1 channel in regulating MSC migration via ATP release and subsequent activation of P2 receptors. (
  • Ase AR, Bernier LP, Blais D, Pankratov Y, Séguéla P. Modulation of heteromeric P2X1/5 receptors by phosphoinositides in astrocytes depends on the P2X1 subunit. (
  • Conclusions- This study reveals for the first time that apart from rapidly desensitizing homomeric P2X1Rs, heteromeric P2X1/4Rs contribute to the sustained component of the purinergic-mediated vasoconstriction in RMCA. (
  • A pyridoxine cyclic phosphate and its 6-azoaryl derivative selectively potentiate and antagonize activation of P2X1 receptors. (
  • 2009). In vitro , ATP-P2 signaling promotes cystic epithelial cell proliferation, chloride-driven fluid secretion and apoptosis. (
  • High glucose and free fatty acids induce beta cell apoptosis via autocrine effects of ADP acting on the P2Y(13) receptor. (
  • The mechanism involved may be distinct from P2 blockade. (
  • The high sensitivity of MRS 2179 has revealed, for the first time in the human gastrointestinal tract, that a P2Y 1 receptor present in smooth muscle probably mediates this mechanism through a pathway that partially involves apamin-sensitive calcium-activated potassium channels. (
  • Three recent reports have examined the relationship between the level of extracellular ATP, the mechanisms underlying purinergic receptors participating in the infection mechanism of HIV-1 in the cell. (
  • These data indicate that ATP and ADP may regulate oligodendrocyte progenitor functions by a mechanism that involves mainly activation of P2Y 1 receptors. (
  • In addition to this mechanism of action indirect activation of cannabinoid receptors and of transient receptor potential vanilloid type-1 (TRPV1) channels have been described. (
  • ATP thus suppresses the nonquantal release via a direct action on presynaptic metabotropic P2 receptors coupled to protein kinase C, whilst adenosine exerts its action mainly by affecting the mechanisms underlying quantal release. (
  • P2X receptors are ligand-gated ion channels, whereas the P1 and P2Y receptors are G protein-coupled receptors. (
  • There are two families of P2 receptors, P2X receptors, which are ligand-gated ion channels, and P2Y receptors, which belong to the group of G protein-coupled receptors. (
  • P2X-receptors are ligand-gated ion channels, whereas P2Y-receptors belong to the superfamily of G-protein-coupled receptors (GPCRs). (
  • They are P2X, i.e. fast cation-selective receptor channels (Na+, K+, Ca2+), possessing low affinity for ATP and responsible for fast excitatory neurotransmission, and P2Y, i.e. slow G protein-coupled metabotropic receptors, possessing higher affinity for the ligand. (
  • Osteoclasts (the bone-resorbing cell) and osteoblasts (the bone-forming cell) display expression of the G protein-coupled P2Y(6) receptor, but the role of this receptor in modulating cell function is unclear. (
  • However, this did not occur in mice that lacked a protein called the P2Y 1 receptor. (
  • Extracellular ATP is one of the most common signalling molecules that induce an increase in the intracellular Ca2+ concentration ([Ca2+]i) via P2 receptors, namely ligand-gated ion channels P2X and/or G protein-coupled P2Y receptors. (
  • Following activation of G-protein-coupled receptors, phospholipase C-β (PLC-β) cleaves phosphatidylinositol 4,5-bisphosphate, releasing diacylglycerol and inositol-1,4,5-trisphosphate (IP3) which diffuses into the cell for activation of IP3 receptors (IP3R) and releasing Ca 2+ from the ER. (
  • Regarding the A3 receptor, selective agonists like N6-(3-iodobenzyl)-5′-N-methylcarboxamidoadenosine (CF101) have been used for the treatment of inflammatory ophthalmic diseases such as dry eye and uveoretinitis. (
  • CONCLUSIONS: Ca2+ is mobilized from intracellular stores in the sheep lens by ATP and epinephrine acting through P2U purinergic and the alpha 1A adrenergic receptors, respectively. (
  • Along the flow of information that step by step instructs microglia on the "right" thing to do, understanding how the activation of a receptor sensing the environment translates an extracellular stimulus into an intracellular signal surely seems important. (
  • 15 The P2Y 1 receptor is responsible for platelet shape change, which occurs through an increase in intracellular calcium triggered by Gα q /phospholipase C activation. (
  • Activation caused a biphasic increase in intracellular [Ca 2+ ] that could be partially blocked by 2-aminoethoxy-diphenyl borate (2-APB), an inhibitor of the IP3 receptor and store-operated channels. (
  • While most of P2Y receptors induce transient elevations of intracellular calcium concentration by activation of intracellular calcium pools and forward these signals as waves which can also be transmitted into neighboring cells, P2X receptors produce calcium spikes which also include activation of voltage-operating calcium channels. (
  • Glutamatergic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) carry the bulk of excitatory synaptic transmission. (
  • Purinergic P2 receptors might be involved in several functions in the gastrointestinal tract, including synaptic transmission and neuromuscular interaction ( 7 , 29 ). (
  • P2X 7 receptor (P2X 7 R), a P2 purinergic receptor, has been implicated in the regulation of synaptic transmission and inflammation. (
  • Vasoactive Amines RELEASE REACTION (platelet granule secretion) Expression of Phospholipid Complex P-Selectin CAMs Promotes platelet recruitment & aggregation via platelet-fibrin + platelet-platelet binding Platelet-Platelet binding promoted by ADP & Thromboxane A2 PLATELET AGGREGATION GpIIb-IIIa Receptor Conformation Integrin complex found on platelets. (
  • The receptor is involved in blood platelet aggregation, vasodilatation and neuromodulation. (
  • These P2Y12-antagonists are used in pharmacotherapy to inhibit platelet aggregation. (
  • These data suggest that ATP-P2 signaling worsens the progression of cyst enlargement and interstitial inflammation in PKD. (
  • Adenosine receptors, in particular adenosine receptors, present anti-inflammatory action in acute and chronic retinal inflammation. (
  • Purinergic receptor type 6 contributes to airway inflammation and remodeling in experimental allergic airway inflammation. (
  • Purinergic signaling has been established as an important feature of inflammation and homeostasis. (
  • Selective induction of endothelial P2Y6 nucleotide receptor promotes vascular inflammation. (
  • A nonspecifie galanin receptor antagonist, M35 enhances C-fiber 'wind-up' and spinal sensitization during inflammation. (
  • mRNA encoding for the human P2Y14-receptor is found in many tissues. (
  • This stimulated us to investigate the expression of P2X and P2Y receptors in human lymphocytes and monocytes with a newly established quantitative mRNA assay for P2 receptors. (
  • Using a quantitative mRNA assay, we assessed the hypothesis that there are specific P2 receptor profiles in inflammatory cells. (
  • In addition, for the first time P2 receptor mRNA expression patterns was studied in CD34 + stem and progenitor cells. (
  • The P2Y6-receptor has a widespread distribution including heart, blood vessels, and brain. (
  • Slow desensitization of the human P2Y6 receptor. (
  • Involvement of P2Y6 receptor in p38 MAPK-mediated COX-2 expression in response to UVB irradiation of human keratinocytes. (
  • Knockout mice reveal a role for P2Y6 receptor in macrophages, endothelial cells, and vascular smooth muscle cells. (
  • After binding onto a specific purinergic receptor, adenosine causes a negative chronotropic effect due to its influence on cardiac pacemakers. (
  • Analogues of the P2 receptor antagonists pyridoxal-5'-phosphate and the 6-azophenyl-2',4'-disulfonate derivative (PPADS), in which the phosphate group was cyclized by esterification to a CH2OH group at the 4-position, were synthesized. (
  • ATP-induced cell migration was inhibited by PPADS, a P2 generic antagonist. (
  • Yoda1-induced cell migration was also prevented by apyrase, an ATP-scavenger as well as PPADS, suggesting that Piezo1 channel activation stimulates cell migration via ATP release and activation of the P2 receptors. (
  • The scope of this review is to discuss the roles of purinergic receptor-induced calcium spike and wave activity and its codification in neurodevelopmental and neurodifferentiation processes. (
  • Islet-resident macrophages expressed functional purinergic receptors, making them exquisite sensors of interstitial ATP levels. (
  • The ACh effects are diminished in the presence of atropine or M3 muscarinic receptor antagonist and in SCs lacking M3 receptors. (
  • Transglial waves represent a means for purinergic signals to act with local specificity to modulate activity or energetics in local neural circuits. (
  • abstract = "To gain insights into the role of purinergic receptors in oligodendrocyte development, we characterized the expression and functional activity of P2 receptors in cultured rat oligodendrocyte progenitors and investigated the effects of ATP and its breakdown products on the migration and proliferation of this immature glial cell population. (
  • It is characterized as a reversible, competitive receptor antagonist. (
  • Ticagrelor is a reversible allosteric antagonist of P2Y12. (
  • Role of the P2Y13 receptor in the differentiation of bone marrow stromal cells into osteoblasts and adipocytes. (
  • In the previous reports, we have shown that quercetin regulates subsets of homomeric ligand-gated ion channels such as glycine, 5- $HT_{3A}$ and ${\alpha}7$ nicotinic acetylcholine receptors. (
  • Mouse Leydig cells express multiple P2X receptor subunits. (
  • 2'-Deoxy-N6-methyladenosine-3',5'-bisphosphate (MRS2179) and 2-chloro-N6-methyl-(N)-methanocarba-2'-deoxyadenosine 3',5'-bisphosphate (MRS2279) are potent and selective antagonists. (
  • The effects of ATP and ADP on cell migration and proliferation were prevented by the P2Y 1 antagonist MRS2179. (
  • P1 receptors are preferentially activated by adenosine and P2Y receptors are preferentially more activated by ATP. (
  • Purinergic antagonists reduced wave propagation through astrocytes to a lesser extent (64-81% of control). (
  • Since massive extracellular release of ATP often occurs after metabolic stress, brain ischemia and trauma, purinergic mechanisms are also correlated to and involved in the etiopathology of many neurodegenerative conditions. (
  • Palmitoylethanolamide (PEA is available as a supplement under the brandnames PeaPure and een PEA-houdend product) exerts anti-inflammatory and analgesic actions via several molecular mechanisms, and probably most important is the direct activation of peroxisome proliferator-activated receptor-α (PPAR-α). (
  • Ovariectomy uncovers purinergic receptor activation of endothelin-dependent natriuresis. (
  • The aim of the present study was to assess the role of this receptor in thrombin-dependent tissue factor-induced thromboembolism. (
  • Conclusions -Our results demonstrate a role of the P2Y 1 receptor in thrombotic states involving thrombin generation and provide further evidence for the potential relevance of this receptor as a target for antithrombotic drugs. (
  • Over the last decade, accumulating evidence suggests that the autocrine and paracrine effects of ATP (through its receptor family P2X and P2Y), could be detrimental for the progression of PKD. (
  • Once released, ATP triggers the activation of purinergic P2 receptors in an autocrine or paracrine fashion. (
  • Purinergic P2Y₂ receptors promote neutrophil infiltration and hepatocyte death in mice with acute liver injury. (
  • Similar results were obtained after intravenous administration of N 6 -methyl-2′-deoxyadenosine-3′:5′-bisphosphate, a selective antagonist of the P2Y 1 receptor, to wild-type mice. (
  • In normal mice, activating the P2Y 1 receptor directly also made the TPSCs release calcium. (