A large plant family in the order Apiales, also known as Umbelliferae. Most are aromatic herbs with alternate, feather-divided leaves that are sheathed at the base. The flowers often form a conspicuous flat-topped umbel. Each small individual flower is usually bisexual, with five sepals, five petals, and an enlarged disk at the base of the style. The fruits are ridged and are composed of two parts that split open at maturity.
A plant genus of the family ACORACEAE, order Arales, subclass Arecidae most notable for Acorus calamus L. root which contains asarone and has been used in TRADITIONAL MEDICINE.
A plant genus in the family MYRTACEAE, order Myrtales, subclass Rosidae. It is best known for allspice from the dried berry of Pimenta diocia.
A plant species in the PIPERACEAE plant family. It is a common spice on foods and is used medicinally to increase gastrointestinal assimilation of other supplements and drugs. Piperine is a key component. Black pepper is picked unripe and heaped for a few days to ferment. White Pepper is the ripe fruit dehulled by maceration in water.
The myrtle plant family of the order Myrtales. It includes several aromatic medicinal plants such as EUCALYPTUS.
A plant family of the order Arales, subclass Arecidae, class Liliopsida (monocot).
A common spice from fruit of PIPER NIGRUM. Black pepper is picked unripe and heaped for a few days to ferment. White Pepper is the ripe fruit dehulled by maceration in water. Piperine is a key component used medicinally to increase gastrointestinal assimilation of other supplements and drugs.
A group of homologous proteins which form the intermembrane channels of GAP JUNCTIONS. The connexins are the products of an identified gene family which has both highly conserved and highly divergent regions. The variety contributes to the wide range of functional properties of gap junctions.
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.
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.
Neurons of the innermost layer of the retina, the internal plexiform layer. They are of variable sizes and shapes, and their axons project via the OPTIC NERVE to the brain. A small subset of these cells act as photoreceptors with projections to the SUPRACHIASMATIC NUCLEUS, the center for regulating CIRCADIAN RHYTHM.
A 43-kDa peptide which is a member of the connexin family of gap junction proteins. Connexin 43 is a product of a gene in the alpha class of connexin genes (the alpha-1 gene). It was first isolated from mammalian heart, but is widespread in the body including the brain.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
A purely physical condition which exists within any material because of strain or deformation by external forces or by non-uniform thermal expansion; expressed quantitatively in units of force per unit area.
A THEOPHYLLINE derivative with broncho- and vasodilator properties. It is used in the treatment of asthma, cardiac dyspnea, and bronchitis.
A METHYLXANTHINE derivative that inhibits phosphodiesterase and affects blood rheology. It improves blood flow by increasing erythrocyte and leukocyte flexibility. It also inhibits platelet aggregation. Pentoxifylline modulates immunologic activity by stimulating cytokine production.
A methyl xanthine derivative from tea with diuretic, smooth muscle relaxant, bronchial dilation, cardiac and central nervous system stimulant activities. Theophylline inhibits the 3',5'-CYCLIC NUCLEOTIDE PHOSPHODIESTERASE that degrades CYCLIC AMP thus potentiates the actions of agents that act through ADENYLYL CYCLASES and cyclic AMP.
Purine bases found in body tissues and fluids and in some plants.
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 class of drugs that act by selective inhibition of calcium influx through cellular membranes.
Agents that control agitated psychotic behavior, alleviate acute psychotic states, reduce psychotic symptoms, and exert a quieting effect. They are used in SCHIZOPHRENIA; senile dementia; transient psychosis following surgery; or MYOCARDIAL INFARCTION; etc. These drugs are often referred to as neuroleptics alluding to the tendency to produce neurological side effects, but not all antipsychotics are likely to produce such effects. Many of these drugs may also be effective against nausea, emesis, and pruritus.
Marked depression appearing in the involution period and characterized by hallucinations, delusions, paranoia, and agitation.
A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence.
A severe emotional disorder of psychotic depth characteristically marked by a retreat from reality with delusion formation, HALLUCINATIONS, emotional disharmony, and regressive behavior.
Cell-surface proteins that bind SEROTONIN and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action.
A selective blocker of DOPAMINE D2 RECEPTORS and SEROTONIN 5-HT2 RECEPTORS that acts as an atypical antipsychotic agent. It has been shown to improve both positive and negative symptoms in the treatment of SCHIZOPHRENIA.
The process of losing secretory granules (SECRETORY VESICLES). This occurs, for example, in mast cells, basophils, neutrophils, eosinophils, and platelets when secretory products are released from the granules by EXOCYTOSIS.
Granulated cells that are found in almost all tissues, most abundantly in the skin and the gastrointestinal tract. Like the BASOPHILS, mast cells contain large amounts of HISTAMINE and HEPARIN. Unlike basophils, mast cells normally remain in the tissues and do not circulate in the blood. Mast cells, derived from the bone marrow stem cells, are regulated by the STEM CELL FACTOR.
Specific molecular sites on the surface of B- and T-lymphocytes which combine with IgEs. Two subclasses exist: low affinity receptors (Fc epsilon RII) and high affinity receptors (Fc epsilon RI).
An immunoglobulin associated with MAST CELLS. Overexpression has been associated with allergic hypersensitivity (HYPERSENSITIVITY, IMMEDIATE).
A class of cell surface receptors for PURINES that prefer ATP or ADP over ADENOSINE. P2 purinergic receptors are widespread in the periphery and in the central and peripheral nervous system.
The secretion of histamine from mast cell and basophil granules by exocytosis. This can be initiated by a number of factors, all of which involve binding of IgE, cross-linked by antigen, to the mast cell or basophil's Fc receptors. Once released, histamine binds to a number of different target cell receptors and exerts a wide variety of effects.
A potent mast cell degranulator. It is involved in histamine release.
A class of cell surface receptors that prefer ADENOSINE to other endogenous PURINES. Purinergic P1 receptors are widespread in the body including the cardiovascular, respiratory, immune, and nervous systems. There are at least two pharmacologically distinguishable types (A1 and A2, or Ri and Ra).
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
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 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.
A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells.
Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.
A subtype of ADENOSINE RECEPTOR that is found expressed in a variety of locations including the BRAIN and endocrine tissues. The receptor is generally considered to be coupled to the GI, INHIBITORY G-PROTEIN which causes down regulation of CYCLIC AMP.
CXCR receptors with specificity for CXCL12 CHEMOKINE. The receptors may play a role in HEMATOPOIESIS regulation and can also function as coreceptors for the HUMAN IMMUNODEFICIENCY VIRUS.
Cell surface glycoproteins that bind to chemokines and thus mediate the migration of pro-inflammatory molecules. The receptors are members of the seven-transmembrane G protein-coupled receptor family. Like the CHEMOKINES themselves, the receptors can be divided into at least three structural branches: CR, CCR, and CXCR, according to variations in a shared cysteine motif.
CXCR receptors that are expressed on the surface of a number of cell types, including T-LYMPHOCYTES; NK CELLS; DENDRITIC CELLS; and a subset of B-LYMPHOCYTES. The receptors are activated by CHEMOKINE CXCL9; CHEMOKINE CXCL10; and CHEMOKINE CXCL11.
A CXC chemokine that is induced by GAMMA-INTERFERON. It is a chemotactic factor for activated T-LYMPHOCYTES and has specificity for the CXCR3 RECEPTOR.
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.
Adherence of cells to surfaces or to other cells.
CCR receptors with specificity for CHEMOKINE CCL27. They may play a specialized role in the cutaneous homing of LYMPHOCYTES.
Activation of the adenosine A1 receptor by an agonist causes binding of Gi1/2/3 or Go protein. Binding of Gi1/2/3 causes an ... The adenosine A1 receptor is one member of the adenosine receptor group of G protein-coupled receptors with adenosine as ... Caffeine may reduce cerebral blood flow in premature infants, it is presumed by blocking vascular A2 ARs. Thus, it may prove ... A1 receptors are also present in smooth muscle throughout the vascular system. The adenosine A1 receptor has been found to be ...
"Chromosomal mapping of A1 and A2 adenosine receptors, VIP receptor, and a new subtype of serotonin receptor". Genomics. 11 (1 ... This is a valuable guide to design potential 5HT1D receptor agonists. When sumatriptan binds there is major conformational ... "Modeling of the agonist binding site of serotonin human 5-HT1A, 5-HT1Dα and 5-HT1Dβ receptors". European Journal of Medicinal ... Agonists might bind in a manner that utilizes an aspartate residue in TM-3 and residues in the TM-4, TM-5 and TM-6. A human ...
"Chromosomal mapping of A1 and A2 adenosine receptors, VIP receptor, and a new subtype of serotonin receptor". Genomics. 11 (1 ... A crystal structure of the A2A receptor bound with the agonist NECA and a G protein-mimic has been published in 2016 (PDB code ... "Chromosomal mapping of A1 and A2 adenosine receptors, VIP receptor, and a new subtype of serotonin receptor". Genomics. 11 (1 ... As a result, Adenosine receptor A2A decreases activity in the Dopamine D2 receptors. The adenosine A2A receptor has also been ...
The A1 receptors couple to Gi/o and decreases cAMP levels, while the A2 adenosine receptors couple to Gs, which stimulates ... Nakav S, Chaimovitz C, Sufaro Y (2008). Bozza P (ed.). "Anti-Inflammatory Preconditioning by Agonists of Adenosine A1 Receptor ... have a purine structure and bind to some of the same receptors as adenosine. Methylxanthines act as competitive antagonists of ... All adenosine receptor subtypes (A1, A2A, A2B, and A3) are G-protein-coupled receptors. The four receptor subtypes are further ...
"Inosine Binds to A3 Adenosine Receptors and Stimulates Mast Cell Degranulation" Mikus EG, Szeredi J, Boer K, Tímári G, Finet M ... a novel specific adenosine A(3) receptor antagonist with adenosine A(3) receptor agonists both in vitro and in vivo". Eur. J. ... 1999). "Cardiac myocytes rendered ischemia resistant by expressing the human adenosine A1 or A3 receptor". FASEB J. 12 (15): ... 1997). "Adenosine inhibits neutrophil degranulation in activated human whole blood: involvement of adenosine A2 and A3 ...
2002). „A3 adenosine receptors in human astrocytoma cells: agonist-mediated desensitization, internalization, and down- ... 1999). „Cardiac myocytes rendered ischemia resistant by expressing the human adenosine A1 or A3 receptor.". FASEB J. 12 (15): ... 1997). „Adenosine inhibits neutrophil degranulation in activated human whole blood: involvement of adenosine A2 and A3 ... Selective human adenosine A3 antagonists based on pyrido[2,1-f]purine-2,4-diones: novel features of hA3 antagonist binding". ...
1992). "Chromosomal mapping of A1 and A2 adenosine receptors, VIP receptor, and a new subtype of serotonin receptor.". Genomics ... overview on a druggable GPCR and on structure-activity relationship analysis and binding requirements of agonists and ... "Chromosomal mapping of A1 and A2 adenosine receptors, VIP receptor, and a new subtype of serotonin receptor". Genomics 11 (1): ... 1992). "Vasodilatory effects of adenosine A2 receptor agonists CGS 21680 and CGS 22492 in human vasculature.". Eur. J. ...
... and reduces inflammation and innate immunity nonselective adenosine receptor antagonist, antagonizing A1, A2, and A3 receptors ... Daly JW, Jacobson KA, Ukena D (1987). "Adenosine receptors: development of selective agonists and antagonists". Prog Clin Biol ... The protein binding is 40%. The volume of distribution may increase in neonates and those suffering from cirrhosis or ... or rather its adenosine-antagonist behavior). Mandal, Ananya. "Caffeine Pharmacology". Website Medical News. Archived from the ...
BDNF binds TrkB receptors whose subsequent activation results in dimerization and autophosphorylation of the receptor. In its ... Katsura, M., Shibasaki, M., Hayashida, S., Torigoe, F., Tsujimura, A., Ohkuma, S. (2006) Increase in expression of a1 and a2/d1 ... and adenosine 30 :50 -cyclic monophosphate response element binding protein activity in an age- and brain region-specific ... Funk, C.K. and Koob, G.F. (2007). A CRF2 agonist administered into the central nucleus of the amygdala decreases ethanol self- ...
One exception to this rule is the receptor for thromboxane A2 (TP) which binds and responds to PGH2 and TXA2 equally well. ... All of the prostanoid receptors are G protein-coupled receptors belonging to the Subfamily A14 of the rhodopsin-like receptor ... TP (TXA2). *Agonists: Carbocyclic thromboxane A2. *I-BOP. *Thromboxane A2 ... Prostaglandin receptors or prostanoid receptors represent a sub-class of cell surface membrane receptors that are regarded as ...
... cells expressing both CysLTR1 and GPR17 receptors exhibit a marked reduction in binding and responding to LTD4 and b) mice ... TP (TXA2). *Agonists: Carbocyclic thromboxane A2. *I-BOP. *Thromboxane A2 ... protein binding. • G-protein coupled peptide receptor activity. • signal transducer activity. • G-protein coupled receptor ... leukotriene receptor activity. • cysteinyl leukotriene receptor activity. • galanin receptor activity. Cellular component. • ...
G protein-coupled receptors (GPCRs) such as DP2 are integral membrane proteins that, when bound by their cognate ligands (or, ... TP (TXA2). *Agonists: Carbocyclic thromboxane A2. *I-BOP. *Thromboxane A2 ... with the C5a receptor, Formyl peptide receptor 1, and Formyl peptide receptor 2 receptors. DP2 has little or no such amino acid ... prostaglandin F receptor activity. • neuropeptide binding. • signal transducer activity. • peptide binding. Cellular component ...
prostaglandin receptor activity. • signal transducer activity. • prostaglandin E receptor activity. • protein binding. ... TP (TXA2). *Agonists: Carbocyclic thromboxane A2. *I-BOP. *Thromboxane A2 ... "Prostanoid Receptors: EP3". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical ... a selective agonist for PGE2 receptor subtype 3". Journal of Leukocyte Biology. 68 (2): 187-93. PMID 10947062.. ...
It binds in a reversible fashion to the adenosine triphosphate (ATP) binding site of the receptor.[28] For the signal to be ... Ephrins (A1, A2, A3, A4, A5, B1, B2, B3). *Erythropoietin (see here instead) ... Decoy receptors: LEVI-04 (p75NTR-Fc). PDGF. *Agonists: Becaplermin. *Platelet-derived growth factor (A, B, C, D) ... It is a receptor tyrosine kinase inhibitor, which acts on the epidermal growth factor receptor (EGFR). ...
... and later gefitinib and erlotinib aiming at the EGF receptor. Sunitinib, an inhibitor of the receptors for FGF, PDGF and VEGF ... Ephrins (A1, A2, A3, A4, A5, B1, B2, B3). *Erythropoietin (see here instead) ... Agonists: Betacellulin. *Epigen. *Heparin-binding EGF-like growth factor (HB-EGF). *Neuregulins (heregulins) (1, 2, 3, 4, 5 ( ... TKIs operate by four different mechanisms: they can compete with adenosine triphosphate (ATP), the phosphorylating entity, the ...
Adenosine A2 Receptor Agonists (4) • Compounds that selectively bind to and activate ADENOSINE A2 RECEPTORS. MeSH ... Adenosine A1 Receptor Antagonists (3) • Compounds that bind to and block the stimulation of ADENOSINE A1 RECEPTORS. MeSH ... Adenosine A2A Receptor Agonists (0) see Adenosine A2 Receptor Agonists. Adenosine A2A Receptor Antagonists (0) see Adenosine A2 ... Adenosine A2B Receptor Agonists (0) see Adenosine A2 Receptor Agonists. Adenosine A2B Receptor Antagonists (0) see Adenosine A2 ...
These probes bind to A.sub.2 and A.sub.3 adenosine receptors and aid in quantifying and characterizing the receptors. The ... This application discloses probes for adenosine receptors which are functionalized congeners of the following compound: ##STR1# ... the binding properties of the functionalized congener to the A-1 adenosine receptor site or the A-2 adenosine receptor, ... which are agonists for A-1 and A-2 adenosine receptors and the sensitivity for quantitativeanalysis of xanthine amine congeners ...
Adenosine A2 Receptor Agonists. Compounds that selectively bind to and activate ADENOSINE A2 RECEPTORS.. 4. 3. Details. ... Adenosine A1 Receptor Agonists. Not Available. 1. 0. Details. Adenosine A1 Receptor Antagonists. Compounds that bind to and ... Adenosine A2 Receptor Antagonists. Compounds that selectively bind to and block the activation of ADENOSINE A2 RECEPTORS.. 4. ... Adenosine. A nucleoside that is composed of ADENINE and D-RIBOSE. Adenosine or adenosine derivativ... more. 11. 99. Details. ...
... is related to prodrugs of adenosine receptor ligands, in general, ie A1- as well as A2-adenosine receptor agonists and ... Document (4) describes in Table III the binding constants for 8-(phenylisopropyl)xanthines at A1- and A2-adenosine receptors. ... Since, according to Table 1 of the application in suit the IC50 adenosine A2 is higher than the IC50 adenosine A1 for racemic N ... As it is said in the application in suit that the claimed compounds provide a selective A1-adenosine receptor antagonistic ...
... adenosine (A1, A2); angiotensin (AT1, AT2); dopamine (D1, D2); endothelin (ETA, ETB); or tachykinin (NK1, NK2, NK3) binding ... Almotriptan is a 5HT1B/1D receptor agonist that is FDA approved for the treatment of migraine attacks in adults with a history ... Almotriptan binds with high affinity to 5-HT1D, 5-HT1B, and 5-HT1F receptors. Almotriptan has weak affinity for 5-HT1A and 5- ... The therapeutic activity of almotriptan in migraine can most likely be attributed to agonist effects at 5-HT1B/1D receptors on ...
A1 and A2 adenosine receptor modulation of contractility in the cauda epididymis of the guinea-pig. British Journal of ... ALEXANDER, SPH, Binding of the antagonist radioligand [H-3]-ZM241385 to A(2A) adenosine receptors in rat brain homogenates In: ... Agonist-occupied A3 adenosine receptors exist within heterogeneous complexes in membrane microdomains of individual living ... A1 adenosine receptor inhibition of cyclic AMP formation and radioligand binding in the guinea-pig cerebral cortex. British ...
Adenosine receptor subtypes and vasodilatation in rat skeletal muscle during systemic hypoxia: a role for A1 receptors. Bryan, ... Activation of adenosine A2 receptors enhances high K(+)-evoked taurine release from rat hippocampus: a microdialysis study. ... or adenosine A2a receptor agonist-induced sleep [8].. *However, the rats perfused with 50 microM CGS21680, an adenosine A2A ... The adenosine A2A receptor interacts with the actin-binding protein alpha-actinin. Burgueño, J., Blake, D.J., Benson, M.A., ...
A.sub.2a receptor antagonists in particular are provided to enhance imm ... Described are uses of A.sub.2a adenosine receptor antagonists and agonists to provide long term modulation of immune responses ... 1990) The adenosine/neutrophil paradox resolved: human neutrophils possess both A1 and A2 receptors that promote chemotaxis and ... 0010] Adenosine binds to P1 purinergic receptors, which are members of the G protein-coupled receptor family. Four subtypes of ...
CCPA binding to rat brain membranes confrrmed binding to an A1 receptor. Solubilized A1 receptors bound [3H]CCPA with similar ... Agonist photoaffinity labeling of A1 adenosine receptors: Persistent activation reveals spare receptors (1986) ... indicating that A2 receptors did not bind [3H]CCPA. Based on the subnanomolar affinity and the high selectivity for A1 ... 2-Alkynyl derivatives of adenosine and adenosine-5-N-ethyluronamides as selective agonists at A\(_2\) adenosine receptors ( ...
We aimed to study efficacy of intrathecal injection of adenosine for post-operative radicular pain after lumbar discectomy. ... This study suggests that intrathecal injection of 1000 micrograms adenosine is a safe and effective method for post-operative ... Adenosine has an analgesic and anti-inflammatory role and its injections are used for perioperative pain management. ... lumbar discectomy who had radicular lower limb pain were treated by 1000 micrograms of intrathecal injection of adenosine in ...
Additional binding partners and modulators of Panx1 activity are A1 and A2 adenosine receptors (Kawamura et al., 2010), Kvβ 3 ... is a relatively late event that is preceded by the rapid opening of the receptor channel and occurs after a prolonged agonist ... Functional modulators include NMDA, A1/A2 adenosine receptors, Kvβ 3 potassium channels and fibroblast growth factor-1 (FGF-1 ... N-methyl-D-aspartate receptor; P2XR, purinergic 2 receptor; TLR, Toll-like receptor, TNFR, tumor necrosis factor receptor; ...
... a mixed adenosine A1 and A2 receptor agonist, nor CGS 21680, a selective adenosine A2A receptor agonist, affected nucleoside ... Characterization of A2A adenosine receptors in human lymphocyte membranes by [3H]-SCH 58261 binding. Varani, K., Gessi, S., ... Chlorofuryl-triazolo-quinazolinamine (CGS-15943; 1 micromol/L), an adenosine A1 and A2 receptor antagonist, and ... lines bound a variety of adenosine agonists and antagonists with affinities characteristic of a brain adenosine A2a receptor [ ...
Activation of the adenosine A1 receptor by an agonist causes binding of Gi1/2/3 or Go protein. Binding of Gi1/2/3 causes an ... The adenosine A1 receptor is one member of the adenosine receptor group of G protein-coupled receptors with adenosine as ... Caffeine may reduce cerebral blood flow in premature infants, it is presumed by blocking vascular A2 ARs. Thus, it may prove ... A1 receptors are also present in smooth muscle throughout the vascular system. The adenosine A1 receptor has been found to be ...
Immunoprecipitation of A1 adenosine receptor-GTP-binding protein complexes in ciliary epithelial cells. Invest Ophthalmol Vis ... epinephrine is a nonselective adrenergic agonist that can activate both α- andβ -adrenergic receptors. Although the signal ... Characterization of the A2 adenosine receptor labeled by [3H]NECA in rat striatal membranes. Mol Pharmacol. 1986;29:331-346. [ ... The orphan receptor cDNA RDC7 encodes an A1 adenosine receptor. EMBO J. 1991;10:1677-1682. [PubMed] ...
Decreased affinity for adenosine receptors may account for the better safety profile of doxofylline compared to theophylline . ... In contrast with other xanthine derivatives, doxofylline does not significantly bind to adenosine alpha-1 or alpha-2 receptors ... enzymes or known PDE enzyme isoforms and did not act as an antagonist at A2 or A2 receptors. The affinity for adenosine A1, A2A ... Identical protein binding. Specific Function. Receptor for adenosine. The activity of this receptor is mediated by G proteins ...
"Chromosomal mapping of A1 and A2 adenosine receptors, VIP receptor, and a new subtype of serotonin receptor". Genomics. 11 (1 ... This is a valuable guide to design potential 5HT1D receptor agonists. When sumatriptan binds there is major conformational ... "Modeling of the agonist binding site of serotonin human 5-HT1A, 5-HT1Dα and 5-HT1Dβ receptors". European Journal of Medicinal ... Agonists might bind in a manner that utilizes an aspartate residue in TM-3 and residues in the TM-4, TM-5 and TM-6. A human ...
The adenosine A1 receptor-selective agonist, CHA, appeared most potent in this modulatory effect when compared to the A2- ... suggested A1 receptor activation by NECA and CGS-21680. The functional similarity between GABAB and adenosine A1, receptors ... an inverse agonist of the benzodiazepine binding site, directly into the motor cortex significantly attenuated EIMI. Further, ... Intrastriatal (IST) administration of adenosine A1-, A1 = A2-, and As-selective agonists, R(-)N6-(2-phenylisopropyl)adenosine ( ...
The second mechanism through which Alzen acts is by blocking serotonin receptors, primarily one called 5HT2A. ... a result of caries reduction of 80 to 85 percent The cardiovascular effects of selective adenosine A1 and A2 receptor agonists ... The MC2 receptor acts in concert with the MC2 receptor accessory protein (MRAP) that is absolutely required for ACTH binding ... is initiated by specific interactions between pathogens and cell surface receptors expressed by phagocytes. ...
... induced via the activation of G protein-coupled adenosine receptors and P2Y nucleotide receptors, as well as by ATP-gated P2X ... induced via the activation of G protein-coupled adenosine receptors and P2Y nucleotide receptors, as well as by ATP-gated P2X ... All three classes of receptors, adenosine, P2X and P2Y are involved in tracheal mucus secretion. This review will summarize the ... All three classes of receptors, adenosine, P2X and P2Y are involved in tracheal mucus secretion. This review will summarize the ...
The known potent A2 adenosine receptor (A2AR) agonist, 5-(N-cyclopropyl) carboxamidoadenosine (CPCA, 2 microM) but not the A1 ... While STa and guanylin bind to the same receptor guanylyl cyclase and raise cell cGMP, the signaling mechanism distal to cGMP ... There is also preliminary evidence that TCR/CD3 may structurally conform to G protein coupled receptors, i.e., having a core ... adenosine receptor agonist, N6-phenyl adenosine (N6-phenyl ADO, 10 microM) markedly increased 125I efflux rate (baseline, 5.9 ...
... effect of single and repeated ECS on the adenosine A1 and A2 receptors, adenylate cyclase, and the adenosine uptake site. ... Benzodiazepine receptor inverse agonists, 1994:. Benzodiazepine-receptor mediated convulsions in infant rats: effects of beta- ... Platelet monamine receptor binding in alcoholics during withdrawal.. Polymorphism of the 5-HT transporter and response to ... Bidirectional effects of chronic treatment with agonists and inverse agonists at the benzodiazepine receptor. ...
1989) showed that radioligand binding to A2 receptors dramatically increases during monocyte differentiation in vitro. ... 1995) The A2b adenosine receptor mediates cAMP responses to adenosine receptor agonists in human intestinal epithelia. J Biol ... 1996) Double tagging recombinant A1- and A2A-adenosine receptors with hexahistidine and the FLAG epitope. Development of an ... 1997) Inosine binds to A3 adenosine receptors and stimulates mast cell degranulation. J Clin Invest 100:2849-2857. ...
... designated A1, A2A, A2B and A3 are currently known. In this study all human subtypes were stably transfected into Chinese ... Four adenosine receptor subtypes of the family of G protein-coupled receptors, ... 8997606 - Repeated treatment with adenosine a1 receptor agonist and antagonist modifies the antic.... 9584206 - Differential ... Adenosine-5-(N-ethylcarboxamide) / pharmacology. Animals. Base Composition. Binding, Competitive. CHO Cells / metabolism*. ...
A2 adenosine receptor) and decreases (A1 adenosine receptor) in cAMP accumulation. Antagonist inhibition curves were steep and ... The complex binding interactions found with adenosine agonists indicate that (3H)CGS 15943 labels both high and low affinity ... caffeine looks like adenosine: caffeine binds to adenosine in. This study reassessed the role of adenosine receptors, and you ... Adenosine antagonist for A1/A2A receptors, caffeine tolerance adenosine receptors in the brain drinks, chocolate, and you feel ...
B.B. (1993). The binding of the adenosine A2 receptor selective SCHIFFMANN, S., LIBERT, F., VASSART, G., DUMONT, J.E. & agonist ... A1 receptors B.A. McCool & J.S. Farroni A1 receptors inhibit amygdala calcium channels also have high a nity for the agonists ... Unless otherwise stated, the holding potential was 1 receptor subtype. (a) The adenosine receptor agonists adenosine (Ade), R- ... Potent of adenosine A1 receptors and 5-nucleotidase in the brain of adenosine receptor antagonists that are selective for the ...
... a potent adenosine receptor agonist with nearly equal affinity at A1 and A2 adenosine receptors, in concentrations ranging from ... And also, the drug-receptor binding assay was performed in order to confirm the presence of A1 and A2 adenosine receptors in ... a specific A2 adenosine receptor antagonist. N6-Cyclopentyladenosine (CPA), a selective A1 adenosine receptor agonist, in doses ... In drug-receptor binding assay, binding of (3H)CCPA to A-1 adenosine receptors of rat striatal membranes was inhibited by CPA ( ...
Chromosomal mapping of A1 and A2 adenosine receptors, VIP receptor, and a new subtype of serotonin receptor. Genomics. 11:225- ... be regulated by receptor-binding ligands via a process of inverse agonism rather than by acting as traditional agonists or ... binding receptor that we reported in an earlier publication (14). The novel receptor, initially designated CCX CKR2 (14) but ... The chemokine SDF-1/CXCL12 binds to and signals through the orphan receptor RDC1 in T lymphocytes. J. Biol. Chem. 280:35760- ...
Selectivity against receptors was tested on the MDS "Profiling" panel, including adenosine A1; adrenergic (α1 and α2 ... Furthermore, CHIR 99021 showed only weak binding (Kd = 4 μmol/l) to a panel of 22 pharmacologically relevant receptors (see ... including insulin receptor substrate 1 (IRS-1), by the tyrosine kinase activity of activated insulin receptor (6,7). Tyrosine- ... phospholipase A2 and C; and tyrosine hydroxylase (Celle LEvescault, France). ...
A known adenosine receptor (AR) agonist was conjugated to polyamidoamine (PAMAM) dendrimer carriers for delivery of the intact ... visualized binding the membrane of cells expressing the A3 receptor but did not bind cells that did not express the receptor. ... Attachment of neutral amide-linked chains or thiourea-containing chains preserved the moderate affinity and efficacy at the A1 ... multivalent dendrimer carriers for delivery of nucleoside signaling molecules to their cell surface G protein-coupled receptors ...
N-[3-(R)-tetrahydrofuranyl]-6-aminopurine riboside, an A1 adenosine receptor agonist, antagonizes catecholamine-induced ... Differential expression of adenosine A1 and A2 receptors in preadipocytes and adipocytes. ... AC: adenyl cyclase; ATGL: denutrin (adipose triglyceride lipase); C/EBP-a: enhancer-binding protein (CCAAT-enhancer-binding ... Adenosine and adenosine receptors. Schematic representation of adenosine synthesis and metabolization. Metabolic pathway ...
  • Tbe 2',3'-dideoxy analogue of the potent A\(_1\) receptor agonist, N\(^6\)-cyclohexyladenosine (CHA), was synthesized as a potential antagonist for the A\(_1\) adenosine receptor. (uni-wuerzburg.de)
  • Competition of 2-alkynyladenosines 2a-d for the antagonist radioligand [\(^3\)H]DPCPX and for the agonist [\(^3\)H]CCPA gave K\(_i\) values in the nanomolar range, and the compounds showed moderate A\(_2\) selectivity. (uni-wuerzburg.de)
  • 1. A method of enhancing an immune response in a host, comprising administering to the host an A.sub.2a receptor antagonist in combination or alternation with a checkpoint inhibitor. (patents.com)
  • Rabbits were pretreated topically with the moderately selective adenosine A 1 antagonist 8-(p-sulfophenyl)theophyline (8-SPT) or the adenosine A 2 antagonist 3,7-dimethyl-l-propargylxanthine (DMPX). (arvojournals.org)
  • Doxofylline does not demonstrate direct inhibition of any histone deacetylase (HDAC) enzymes or known PDE enzyme isoforms and did not act as an antagonist at A2 or A2 receptors. (drugbank.ca)
  • Structure of native agonists of the purinergic receptors, including both P2Rs (1-8) and ARs (9), and structures of agonist (10-20) and antagonist (21-37) ligands developed for the ARs, as described in the text. (frontiersin.org)
  • Antagonist-agonist combinations as therapies for heroin addiction : back to the future? (isni.org)
  • In competition with antagonist radioligand biphasic curves were observed for agonists. (biomedsearch.com)
  • Antagonist inhibition curves were steep and best described by a one-site binding model. (kzeng.info)
  • Caffeine is a competitive antagonist at adenosine receptors. (kzeng.info)
  • Consistent with a role for CXCR7 in cell survival and adhesion, a specific, high affinity small molecule antagonist to CXCR7 impedes in vivo tumor growth in animal models, validating this new receptor as a target for development of novel cancer therapeutics. (rupress.org)
  • CADO inhibition of barium currents was also sensitive to the A1 antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX). (gotomydoctor.com)
  • Although incubation of monocytes with IB-MECA, a compound purported to act as an adenosine A 3 receptor agonist, reduced LPS-induced TNF-α production, this effect of IB-MECA was inhibited by the A 2A selective antagonist ZM241385 but not by the A 3 receptor antagonist MRS1220. (elsevier.com)
  • To address the signal transduction mechanism responsible for the anti-inflammatory effects of ATL313 in equine monocytes, production of cAMP was compared in the presence and absence of either the adenosine A 2A receptor antagonist ZM241385 or the adenosine A 2B receptor antagonist MRS1706. (elsevier.com)
  • OC differentiation was studied as TRAP+ multinucleated cells following M-CSF/RANKL stimulation of either primary murine bone marrow cells or the murine macrophage line, RAW264.7, in presence/absence of the A(2A)R agonist CGS21680, the A(2A)R antagonist ZM241385, PKA activators (8-Cl-cAMP 100 nM, 6-Bnz-cAMP) and the PKA inhibitor (PKI). (nih.gov)
  • a ligand of M1 and M5, a ligand of M2 and M5, and a ligand of M3 and M5), but until both a selective agonist and a selective antagonist of the M5 receptor are developed this data must be considered merely theoretical. (wikidoc.org)
  • 2014). "Discovery, Synthesis and Characterization of a Highly Muscarinic Acetylcholine Receptor (mAChR)-Selective M5 -Orthosteric Antagonist, VU0488130 (ML381): A Novel Molecular Probe" . (wikidoc.org)
  • Photic Induction of Fos Protein in the Suprachiasmatic Nucleus Is Inhibited by the NMDA Receptor Antagonist MK-801. (ke-i.org)
  • Rescue of locomotor impairment in dopamine D2 receptor-deficient mice by an adenosine A2A receptor antagonist. (ke-i.org)
  • DPCPX is a potent and selective A1 adenosine receptor antagonist, both in vitro and in vivo. (emmx.com)
  • 1,3-Dipropyl-8-phenylxanthine is a selective A1 adenosine antagonist. (emmx.com)
  • PSB 36 is a Potent and selective A1 adenosine receptor antagonist with binding affinities of 0.12, 187, 552, 6500 and 2300 nM for rA1, hA2B, rA2A, rA3 and hA3 receptors respectively. (emmx.com)
  • SLV 320 is a potent and selective adenosine A1 receptor antagonist (Ki values are 1, 200, 398 and 3981 nM at human A1, A3, A2A and A2B receptors respectively). (emmx.com)
  • PSB 1115 is a highly selective, water-soluble, human A2B adenosine receptor antagonist. (emmx.com)
  • NMDA receptor antagonist. (emmx.com)
  • I am interested in how activation of one of these classes of receptor leads to modification of the response to other receptor classes (cross-talk), as well as how different ligands can provoke different signalling profiles at the same receptor (agonist bias). (nottingham.ac.uk)
  • Cannabinoid receptors and their ligands: beyond CB₁ and CB₂. (nottingham.ac.uk)
  • G protein-coupled receptor list: recommendations for new pairings with cognate ligands. (nottingham.ac.uk)
  • 2-(4,5-dihydro-1H-imidazol-2-yl)indazole (indazim) derivatives as selective I(2) imidazoline receptor ligands. (isni.org)
  • These cells are valuable systems for further characterization of specific receptor subtypes and for the development of new ligands. (biomedsearch.com)
  • Development of a screening assay for ligands to the estrogen receptor based on magnetic microparticles and LC-MS. (storysteel.gq)
  • We validate that the interaction of VCP746 with the A 1 AR is consistent with a bitopic mode of receptor engagement (i.e., concomitant association with orthosteric and allosteric sites) and that the compound displays biased agonism relative to prototypical A 1 AR ligands. (pnas.org)
  • Thus, this study provides proof of concept that bitopic ligands can be designed as biased agonists to promote on-target efficacy without on-target side effects. (pnas.org)
  • Several allosteric ligands to these receptors have been identified and these appear to bind within the seven transmembrane region. (europeanpharmaceuticalreview.com)
  • GPCRs respond to various ligands extracellularly, such as amines, peptides, hydrophobic effectors, hormones, small proteins and volatiles, which allows the receptors to activate the G-proteins intracellularly. (europeanpharmaceuticalreview.com)
  • The lack of selective M5 receptor ligands is one of the main reasons that the medical community has such a limited understanding of the M5 receptors effects as the possibility that any and/or all effects of non-selective ligands may be due to interactions with other receptors can not be ruled out. (wikidoc.org)
  • In addition, both acid production and radioligand binding of adenosine analogs to isolated cell membranes were potently blocked by selective A2BR antagonists, whereas ligands for A 1 , A 2A , and A 3 adenosine receptors failed to abolish activation. (physiology.org)
  • The aim of this work was the development and biological test of adenosine receptor ligands which are suitable for in vivo PET examinations. (otka-palyazat.hu)
  • The biological distribution of the ligands as well as their binding kinetics to the receptors was tested in vivo by dynamic PET scans and ex vivo or in vitro experiments. (otka-palyazat.hu)
  • Compounds that bind to and block the stimulation of ADENOSINE A1 RECEPTORS. (nih.gov)
  • Stimulation of the A1 receptor has a myocardial depressant effect by decreasing the conduction of electrical impulses and suppressing pacemaker cell function, resulting in a decrease in heart rate. (wikipedia.org)
  • 3-5 The spinal administration of adenosine itself does not produce analgesia in normal rats to acute noxious stimulation. (asahq.org)
  • 7 A common problem with administration of direct agonists, such as adenosine itself, is adverse effects caused by stimulation of all receptors, not just those involved in the therapeutic effect. (asahq.org)
  • Stimulation of α 1 adrenergic receptors in the PVN increases sympathetic outflow, but the cellular mechanisms remain unclear. (aspetjournals.org)
  • Background and purpose: Desensitization of somatodendritic 5-HT1A receptors is involved in the mechanism of action of several antidepressants, but the rapidity of this effect and the amount of agonist stimulation needed are unclear. (cancer-colorectal.com)
  • In this study, we demonstrate that, following TLR stimulation, macrophages upregulate the adenosine 2b receptor (A2bR) to enhance their sensitivity to immunosuppressive extracellular adenosine. (jimmunol.org)
  • After TLR stimulation, macrophages alter their metabolism and release low levels of ATP, which is rapidly converted into immunosuppressive adenosine via CD39-mediated hydrolysis. (jimmunol.org)
  • Results of experiments performed with one of the adenosine receptor agonists (ATL313) and selective adenosine receptor antagonists confirmed that inhibition of LPS-induced production of TNF-α occurred via stimulation of A 2A receptors. (elsevier.com)
  • Downregulation of P2X7 and upregulation of CD73 in Treg after antigenic stimulation may be an important mechanism to maintain the ability of Treg to generate immunosuppressive adenosine. (physiology.org)
  • On murine T lymphocytes the A2aR is highly expressed ( 20 ), and after T-cell receptor (TCR) stimulation, A2aR mRNA levels increase by a factor of ∼10 ( 16 ). (physiology.org)
  • Results of experiments performed with selective adenosine receptor antagonists indicated that functional effects of ATL313 were via stimulation of A 2A receptors. (elsevier.com)
  • For a better understanding how adenosine A(2A)R stimulation regulates OC differentiation, we dissected the signalling pathways involved in A(2A)R signalling. (nih.gov)
  • Our findings demonstrate that inhibition of adenosine transport via hENT1 in endothelial cells cultured in 25 mmol/L D-glucose could be due to stimulation of P2Y2 purinoceptors by ATP, which is released from these cells in response to D-glucose. (slideshare.net)
  • however, stimulation of this receptor is known to effectively decrease cyclic AMP levels and downregulate the activity of protein kinase A (PKA). (wikidoc.org)
  • The adenosine A1 receptor is one member of the adenosine receptor group of G protein-coupled receptors with adenosine as endogenous ligand. (wikipedia.org)
  • When sumatriptan binds there is major conformational change in both ligand and receptor in the binding pocket. (wikipedia.org)
  • However, recent evidence showed that many other receptors, such as G protein-coupled receptors and ligand-gated ion channels, are also directly involved in mast cell degranulation, the release of inflammatory mediators such as histamine, serine proteases, leukotrienes, heparin, and serotonin. (frontiersin.org)
  • ATP acts via P2X receptors (P2XRs), which are ligand-gated cation channels, to induce mast cell degranulation ( Bulanova and Bulfone-Paus, 2010 ). (frontiersin.org)
  • Acute and chronic effects of the benzodiazepine receptor ligand FG 7142: proconvulsant properties and kindling. (isni.org)
  • Unlike many other chemokine receptors, ligand activation of CXCR7 does not cause Ca 2+ mobilization or cell migration. (rupress.org)
  • This is the first example showing that it is feasible to modulate and even enhance the pharmacological profile of a ligand of a GPCR based on conjugation to a nanocarrier and the precise structure of the linking group, which was designed to interact with distal extracellular regions of the 7 transmembrane-spanning receptor. (biomedcentral.com)
  • In the current study, we have rationally designed a novel A 1 AR ligand (VCP746)-a hybrid molecule comprising adenosine linked to a positive allosteric modulator-specifically to engender biased signaling at the A 1 AR. (pnas.org)
  • Glutamate receptors have a large extracellular N-terminus (often likened to a clam) which binds the orthosteric (endogenous) ligand. (europeanpharmaceuticalreview.com)
  • Many of the receptors have accessory proteins which either facilitate trafficking to the plasma membrane or influence the specificity of the ligand 8 . (europeanpharmaceuticalreview.com)
  • Whereas some reports claim that the receptor induces signaling following ligand binding, recent findings in zebrafish suggest that CXCR7 functions primarily by sequestering the chemokine CXCL12. (wikidoc.org)
  • However, another recent study has provided evidence that ligand binding to CXCR7 activates MAP kinases through Beta-arrestins, and thus has functions beyond ligand sequestration. (wikidoc.org)
  • It is concluded that agonist-specific thennodynamic characteristics of ligand binding to a2-receptors of human platelets can only be investigated by regarding differences between high and low affinity agonist binding. (uni-wuerzburg.de)
  • [1] Binding of the endogenous ligand acetylcholine to the M 5 receptor triggers a number of cellular responses such as adenylate cyclase inhibition, phosphoinositide degradation, and potassium channel modulation. (wikidoc.org)
  • By the chemical reaction of different xantine type molecules and [11C] methyl iodide we produced several A2A adenosine receptor specific antagonists for in vivo testing the receptor ligand interactions. (otka-palyazat.hu)
  • The protocols worked out provide a firm base for having been receptor/ligand research at the PET Center of the University of Debrecen. (otka-palyazat.hu)
  • Since studies regarding postoperative analgesic effects of adenosine are not sufficient to overcome controversy in the literature, in this study, we aimed to determine the efficacy of intrathecal adenosine injection for relief of neuropathic pain after lumbar uni-level discectom. (biomedcentral.com)
  • 11,14,15 Thus, the effects of adenosine or T62 after nerve injury are totally abolished by destruction of noradrenergic terminals or administration of α 2 -adrenoceptor antagonists. (asahq.org)
  • Several studies have also suggested that the beneficial effects of adenosine occur through the effects of the A2AR and A2BR ( 7 , 22 , 27 , 43 ). (physiology.org)
  • Of the four known adenosine receptors (A 1 , A 2A , A 2B , and A 3 ), A 1 receptor (A 1 R) and A 2A receptor (A 2A R) are primarily responsible for the central effects of adenosine ( Dunwiddie and Masino, 2001 ). (jneurosci.org)
  • Thus, we propose a novel mechanism whereby IFN-γ contributes to host defense by desensitizing macrophages to the immunoregulatory effects of adenosine. (jimmunol.org)
  • Adenosine which has four subtypes of A1, A2a, A2b and A3, is an endogenous protein nucleotide. (biomedcentral.com)
  • This rise in endogenous levels of adenosine then leads to the activation of ocular adenosine receptors and is in part responsible for the ocular hypotensive action of epinephrine. (arvojournals.org)
  • In the presence of GTP all receptors were converted to a single low affinity state indicating functional coupling to endogenous G proteins. (biomedsearch.com)
  • As a breakdown product of ATP, adenosine is an endogenous purine nucleoside that modulates many physiological processes in all cells of the body. (physiology.org)
  • The A2AR is expressed in lung tissues, where it is activated by endogenous/exogenous adenosine or A2AR agonists and where it exerts anti-inflammatory effects ( 24 , 39 , 45 ). (physiology.org)
  • Adenosine is an endogenous nucleoside that regulates many physiological processes by activating one or more adenosine receptor subtypes, namely A 1 , A 2A , A 2B and A 3 . (elsevier.com)
  • Adenosine is an endogenous purine nucleoside that modulates a wide range of physiological functions ( 1 ). (jimmunol.org)
  • Acting on the loose primary platelet aggregates, thrombin (1) propagates aggregation by releasing ADP from platelet granules and allowing the formation of thromboxane A2, (2) provides structural stability to the thrombus by enmeshing the tight platelet aggregate with a fibrin network, and (3) makes the platelet‐rich thrombus resistant to endogenous fibrinolysis by releasing the main fibrinolysis inhibitor PAI‐1 from platelets and inducing the formation of TAFI. (ahajournals.org)
  • This nucleoside, acting at one or more of its receptors, is a potent endogenous anti-inflammatory mediator. (biomedcentral.com)
  • Through a reorganization of these heteroreceptor complexes upon chronic dopaminergic treatment a pathological and prolonged inhibition of D2R receptor protomer signaling can develop with motor inhibition and wearing off of the therapeutic effects of levodopa and dopamine receptor agonists. (springer.com)
  • However, exploitation of the 3D structures of GPCRs is now preferable due to the elucidation of the structure of rhodopsin17, followed by those of the beta118, beta219, adrenergic, adenosine A2A20, dopamine D321, CXCR4 chemokine22, histamine H1 receptors23 and recently sphingosine 1-phosphate receptor24 and the M2 muscarinic acetylcholine receptor25. (europeanpharmaceuticalreview.com)
  • KANNA 20:1 extract (Sceletium tortuosum) Kanna works by interacting with the brain`s dopamine and serotonin receptors, promotes healthy wellbeing, and is used as a mood enhancer. (flippingbook.com)
  • He contributed to the first cloning of the D2 dopamine receptor ( Nature ) and achieved the first expression of a mammalian voltage-gated potassium channel ( Science ), and first functional demonstration of its heteropolymerisation ( Neuron ). (edu.au)
  • Compounds that bind to and inhibit the enzymatic activity of acetaldehyde dehydrogenases. (nih.gov)
  • Drugs that inhibit ADENOSINE DEAMINASE activity. (nih.gov)
  • Compounds that bind to and inhibit the action of ADENYLYL CYCLASES. (nih.gov)
  • anxiety have implicated the basolateral complex (BLA), as Previous work has demonstrated that adenosine receptors being centrally important in both the acquisition and may act presynaptically in the amygdala to inhibit both expression of fear/apprehension-related behaviours (re- excitatory and inhibitory transmission (Heinbockel & viewed in Davis, 1992). (gotomydoctor.com)
  • The major adenosine receptor complexes in the striato-pallidal GABA neurons can be the A2AR-D2R and A2AR-D2R-mGluR5 receptor complexes, in which A2AR protomers and mGluR5 protomers can allosterically interact to inhibit D2R protomer signaling. (springer.com)
  • Barbiturates inhibit binding of radioligands to A 1(Ri) adenosine receptors of rat brain membranes. (uni-wuerzburg.de)
  • Barbiturates also inhibit the binding of radioligands to solubilized A1receptors, and saturation and kinetic experiments suggest that this is due to a competitive antagonism. (uni-wuerzburg.de)
  • This provides a switch mechanism by which low and high concentrations of adenosine inhibit and stimulate, respectively, glutamate release. (jneurosci.org)
  • The main biochemical characteristic of the A 1 R-A 2A R heteromer is the ability of A 2A R activation to reduce the affinity of the A 1 R for agonists, providing a switch mechanism by which low and high concentrations of adenosine inhibit and stimulate, respectively, glutamatergic neurotransmission. (jneurosci.org)
  • The results of previous studies indicate that adenosine analogues inhibit lipopolysaccharide (LPS)-induced production of reactive oxygen species (ROS) by equine neutrophils primarily through activation of A 2A receptors. (elsevier.com)
  • Collectively, the results of the current study indicate that adenosine analogues inhibit LPS-induced production of TNF-α by equine monocytes primarily via activation of adenosine A 2A receptors and do so in a cAMP-dependent manner. (elsevier.com)
  • However, genetic deletion of CD73 in mice is associated with a proinflammatory phenotype and CD73-derived adenosine appears to be quantitatively sufficient to inhibit platelet activation, and leukocyte adhesion to the vascular endothelium in vivo ( 15 ) by acting through the A2aR ( 47 ). (physiology.org)
  • Aside from its action on the endothelium, A2aR agonists inhibit T-cell activation through increasing cAMP levels, which acts immunosuppressive ( 39 ). (physiology.org)
  • as the functionally predominant purinergic receptors on murine T cells. (aspetjournals.org)
  • Previous studies of the expression of purinergic receptors in subsets of lymphocytes have been limited to receptors for ATP. (aspetjournals.org)
  • This study explored the role of endogenously formed adenosine in modulating NF-κB activity and cytokine/chemokine release from murine Treg and effector T cells (Teff) including key enzymes/purinergic receptors of extracellular ATP catabolism. (physiology.org)
  • While ATP primarily acts as a proinflammatory signal on purinergic P2 receptors, its degradation product adenosine signals through P1 purinergic receptors, mediating both anti- and proinflammatory effects depending on the receptor subtype. (physiology.org)
  • The balance of these two molecules can be generated by extracellular nucleotides, such as adenosine 5'-triphosphate (ATP) and adenosine (Ado), which activate the purinergic receptors system. (biomedcentral.com)
  • To avoid these undesirable effects, indirect approaches, such as allosteric adenosine receptor modulation or inhibition of adenosine kinase 9,10 or adenosine deaminase, 11 have been examined and show antinociceptive effects in neuropathic rats. (asahq.org)
  • 12. The method according to claim 5 wherein an adenosine deaminase inhibitor which prevents the decomposition of adenosine, is administered. (patentsencyclopedia.com)
  • The half-life of extracellular adenosine is on the order of seconds, as it is removed from the extracellular space either by adenosine deaminase, which converts it to inosine, or by cellular reuptake via equilibrative or concentrative nucleoside transporters ( 6 , 7 ). (jimmunol.org)
  • The A1 subtype showed the typical pharmacological profile with 2-chloro-N6-cyclopentyladenosine (CCPA) as the agonist with the highest affinity and a marked stereoselectivity for the N6-phenylisopropyladenosine (PIA) diastereomers. (biomedsearch.com)
  • 2 CADO, adenosine, and the A1 subtype-selective agonists N6-(L-2-Phenylisopropyl)adenosine (R- PIA) and 2-chloro-N6-cyclopentyladenosine (CCPA) reversibly modulated whole cell Ba2+ currents in a concentration-dependent fashion. (gotomydoctor.com)
  • For example, the A1 adenosine receptor *Author for correspondence at: Department of Medical subtype is classically associated with the inhibition of Pharmacology and Toxicology, The Texas A&M Univ. (gotomydoctor.com)
  • These results indicate that the adenosine receptor subtype responsible for regulation of LPS-induced cytokine production by equine monocytes is the A 2A receptor. (elsevier.com)
  • The renewed interest in the adenosine A 2B receptor (A2BR) subtype can be traced by studies in which the introduction of new genetic and chemical tools has widened the pharmacological and structural knowledge of this receptor as well as its potential therapeutic use in cancer and inflammation- or hypoxia-related pathologies. (physiology.org)
  • In the acid-secreting parietal cells of the gastric mucosa, the use of various radioligands for adenosine receptors suggested the presence of the A 2 adenosine receptor subtype(s) on the cell surface. (physiology.org)
  • Described are uses of A.sub.2a adenosine receptor antagonists and agonists to provide long term modulation of immune responses. (patents.com)
  • In this review we propose that adenosine could be a key element in the development of new strategies for limit lipoinflammation and regulate metabolic homeostasis through modulation of adipocyte-macrophage dialog. (elsevier.es)
  • ADENOSINE is recognized to play a role in modulation of nociceptive transmission in the spinal cord. (asahq.org)
  • Among these indirect approaches, allosteric adenosine receptor modulation represents a novel drug development direction to potentiate A1 receptor function and agonist binding via a conformation change. (asahq.org)
  • Biochemical and pharmacological role of A1 adenosine receptors and their modulation as novel therapeutic strategy In: ed Protein Reviews. (eurekaselect.com)
  • The concepts of allosteric modulation and biased agonism are revolutionizing modern approaches to drug discovery, particularly in the field of G protein-coupled receptors (GPCRs). (pnas.org)
  • In the present study, we demonstrate that heteromerization of adenosine A 1 receptors (A 1 Rs) and A 2A receptors (A 2A Rs) allows adenosine to exert a fine-tuning modulation of glutamatergic neurotransmission. (jneurosci.org)
  • Patterns of A2A Extracellular Adenosine Receptor Expression in Different Functional Subsets of Human Peripheral T Cells. (aspetjournals.org)
  • We have recently shown that extracellular adenosine enhances human pulmonary (EC) barrier via activation of adenosine receptors (ARs) in cell cultures. (physiology.org)
  • In this study, we investigated the effect of IFN-γ on TLR-activated macrophages, and we reveal that IFN-γ sustains inflammatory macrophage activation by attenuating their sensitivity to extracellular adenosine. (jimmunol.org)
  • Extracellular adenosine has an important role in regulating the severity of inflammation during an immune response. (jimmunol.org)
  • Therefore, acute increases in extracellular adenosine levels tend to only have local and tissue-limited effects. (jimmunol.org)
  • During inflammation, increases in extracellular adenosine levels effectively turn off the local inflammatory response to protect against excessive cellular damage to the surrounding tissue ( 2 ). (jimmunol.org)
  • Cells that express one or more of the four G protein-coupled adenosine receptors (AR) subtypes (A1, A2A, A2B, and/or A3) have the capacity to respond to extracellular adenosine. (jimmunol.org)
  • Acute ethanol (alcohol) exposure increases extracellular adenosine, which mediates the ataxic and hypnotic/sedative effects of alcohol, while chronic ethanol exposure leads to downregulated adenosine signaling that underlies insomnia, a major predictor of relapse. (ke-i.org)
  • In the search for more selective A2-receptor agonists and on the basis that appropriate substitution at C2 is known to impart selectivity for A\(_2\) receptors, 2-alkynyladenosines 2a-d were resynthesized and evaluated in radioligand binding, adenylate cycla.se, and platelet aggregation studies. (uni-wuerzburg.de)
  • The tritiated analogue of 2-chloro-N6-cyclopentyladenosine (CCPA), an adenosine derivative with subnanomolar affinity and a 10000-fold selectivity for A1 adenosine receptors, has been examined as a new agonist radioligand. (uni-wuerzburg.de)
  • 3H]2-(2-benzofuranyl)-2-imidazoline: a new selective high affinity radioligand for the study of rabbit brain imidazoline I2 receptors. (isni.org)
  • showed that radioligand binding to A2 receptors dramatically increases during monocyte differentiation in vitro. (aspetjournals.org)
  • Information about the lymphocyte subset-specific expression of adenosine receptors would be useful, but it has been difficult to obtain sufficient quantities of cells to analyze expression of Ado receptors in biochemical or radioligand binding assays, particularly in the minor subpopulations of lymphocytes. (aspetjournals.org)
  • In this study all human subtypes were stably transfected into Chinese hamster ovary (CHO) cells in order to be able to study their pharmacological profile in an identical cellular background utilizing radioligand binding studies (A1, A2A, A3) or adenylyl cyclase activity assays (A2B). (biomedsearch.com)
  • Radioligand-binding experiments in cotransfected cells and rat striatum showed that a main biochemical characteristic of the A 1 R-A 2A R heteromer is the ability of A 2A R activation to reduce the affinity of the A 1 R for agonists. (jneurosci.org)
  • In the present study, we use radioligand-binding, coimmunoprecipitation, bioluminescence resonance energy transfer (BRET) and time-resolved fluorescence resonance energy transfer (TR-FRET) techniques to demonstrate that A 1 R and A 2A R form A 1 R-A 2A R heteromers in mammalian cells and in striatal glutamatergic nerve terminals. (jneurosci.org)
  • Procedures - Radioligand binding experiments were performed to compare binding affinities of adenosine receptor agonists to equine adenosine A 1 , A 2A , and A 3 receptor subtypes. (elsevier.com)
  • My central area of research concerns the pharmacology and biochemistry of G protein-coupled receptors (in particular, cannabinoid, adenosine and glutamate) in the CNS and peripheral tissues. (nottingham.ac.uk)
  • Goadsby, P.J., Serotonin 5-HT1B/1D receptor agonists in migraine - Comparative pharmacology and its therapeutic implications. (wikipedia.org)
  • Comparative pharmacology of human adenosine receptor subtypes - characterization of stably transfected receptors in CHO cells. (biomedsearch.com)
  • In this study we present for the first time the comparative pharmacology of all known human adenosine receptor subtypes. (biomedsearch.com)
  • In fact, adenosine receptor activation can subtypes of P1 receptors can be distinguished from one even prevent the acquisition of amygdala kindling (Abdul- another by receptor pharmacology or by examination of the signal transduction pathways to which the individual receptors couple. (gotomydoctor.com)
  • A1 adenosine receptors, A1 AR agonists, partial agonists, antagonists and allosteric modulators, pharmacology of A1 AR, structure- activity relationships of A1 AR. (eurekaselect.com)
  • Borea PA, Gessi S, Merighi S, Vincenzi F, Varani K. Pharmacology of adenosine receptors: the state of the art. (eurekaselect.com)
  • Through the receptor heteromerization the allosteric receptor-receptor interactions can develop and produce alterations in recognition including novel allosteric binding sites, pharmacology, signaling, and trafficking of the participating receptors (receptor protomers). (springer.com)
  • A1 receptors are implicated in sleep promotion by inhibiting wake-promoting cholinergic neurons in the basal forebrain. (wikipedia.org)
  • It promotes wakefulness by blocking adenosine A 2A receptors (A 2A Rs) in the brain, but the specific neurons on which caffeine acts to produce arousal have not been identified. (kzeng.info)
  • We have utilized whole-cell voltage-clamp electrophysiology to examine the modulatory e ects of CADO and other adenosine receptor agonists on voltage-gated calcium channels in dissociated basolateral amygdala neurons. (gotomydoctor.com)
  • 1987). Unlike A1 receptors, A2 adenosine receptors appear to couple to cholera toxin- Neurons were prepared from coronal brain slices of juvenile sensitive G proteins and can stimulate cyclic AMP male rats (*P17 ± P28) as previously described (McCool & accumulation. (gotomydoctor.com)
  • In this study, we determined the role of α 1 adrenergic receptors in the regulation of glutamatergic and GABAergic synaptic inputs to spinally projecting PVN neurons. (aspetjournals.org)
  • However, phenylephrine failed to increase the firing of most labeled PVN neurons in the presence of GABA A and ionotropic glutamate receptor antagonists. (aspetjournals.org)
  • Thus, these data suggest that activation of α 1 adrenergic receptors increases the excitability of PVN presympathetic neurons primarily through augmentation of glutamatergic tone and attenuation of GABAergic inputs. (aspetjournals.org)
  • His later research uncovered the mechanisms of plasticity of G-protein receptor coupling in neurons that are transforming thinking regarding opioid tolerance and ion channel plasticity in chronic pain states. (edu.au)
  • Activation of the adenosine A1 receptor by an agonist causes binding of Gi1/2/3 or Go protein. (wikipedia.org)
  • This study evaluated the role of adenosine receptor activation in epinephrine-induced changes in ocular function. (arvojournals.org)
  • Although the signal transduction mechanisms associated with adrenergic receptor activation are diverse, studies have identified a relationship between the ocular hypotensive action of adrenergic agonists in their ability to stimulate adenylate cyclase. (arvojournals.org)
  • In recent years, it has been realized that purinergic signaling, induced via the activation of G protein-coupled adenosine receptors and P2Y nucleotide receptors, as well as by ATP-gated P2X receptors, plays a significant role in mast cell degranulation. (frontiersin.org)
  • Adenosine 5′-triphosphate (ATP, compound 3 in Figure 1 ) is abundant in mast cells, stored in granules and secreted upon activation. (frontiersin.org)
  • 1997). This anticonvulsant activity of CADO highly integrative role in the sense/memory-response is dose-dependent and blocked by ca eine, suggesting that pathway and is believed to occupy a pivotal position in activation of adenosine heptahelical receptors in the the regulation of fear and anxiety. (gotomydoctor.com)
  • However, treatment with full A1 AR agonists has been associated with numerous challenges like cardiovascular side effects, off-target activation as well as desensitization of A1 AR leading to tachyphylaxis. (eurekaselect.com)
  • Allosteric enhancer of A1 AR is found to be potent for the treatment of neuropathic pain, culminating the side effects related to off-target tissue activation of A1 AR. (eurekaselect.com)
  • Furthermore, activation of α 1 adrenergic receptors with phenylephrine or cirazoline significantly decreased the frequency of spontaneous inhibitory postsynaptic currents and miniature inhibitory postsynaptic currents, and this effect also was blocked by corynanthine. (aspetjournals.org)
  • Conclusions and implications: Rat somatodendritic 5-HT1A receptors controlling hippocampal 5-HT release were rapidly desensitized by chronic activation with a high-efficacy 5-HT1A agonist, but not by chronic activation with a partial agonist. (cancer-colorectal.com)
  • models of 5-HT1A receptor activation (Koek microdialysis. (cancer-colorectal.com)
  • Some GPCR are enriched or excluded from caveolae whereas certain GPCR reportedly translocate out of or into caveolae upon activation by an agonist. (aspetjournals.org)
  • Cyclic AMP-binding capacities and histone kinase activation in subcellular components of neocortical tissue. (meta.org)
  • In addition, activation of the P2X7 receptor, present on immune cells, triggers membrane permeabilization to medium-sized molecules and thereby may permit the cellular exit of ATP ( 28 ). (physiology.org)
  • Conclusions and Clinical Relevance - Results indicated that activation of A 2A receptors exerted anti-inflammatory effects on equine neutrophils and that stable, highly selective adenosine A 2A receptor agonists may be developed for use in management of horses and other domestic animals with septic and nonseptic inflammatory diseases. (elsevier.com)
  • Activation of adenosine A(2A) receptor reduces osteoclast formation via PKA- and ERK1/2-mediated suppression of NFκB nuclear translocation. (nih.gov)
  • We previously reported that adenosine, acting at adenosine A(2A) receptors (A(2A)R), inhibits osteoclast (OC) differentiation in vitro (A(2A)R activation OC formation reduces by half) and in vivo. (nih.gov)
  • A(2A)R activation inhibits OC differentiation and regulates bone turnover via PKA-dependent inhibition of NFκB nuclear translocation, suggesting a mechanism by which adenosine could target bone destruction in inflammatory diseases like rheumatoid arthritis. (nih.gov)
  • Adenosine A 2A R activation increased cAMP production and increased PKA activation. (nih.gov)
  • 1. Inhibition of Nitrobenzylthioinosine-Sensitive Adenosine Transport by Elevated D-Glucose Involves Activation of P2Y2 Purinoceptors in Human Umbilical Vein Endothelial Cells Jorge Parodi, Carlos Flores, Claudio Aguayo, M. Isolde Rudolph, Paola Casanello, Luis SobreviaAbstract-Chronic incubation with elevated D-glucose reduces adenosine transport in endothelial cells. (slideshare.net)
  • 1994). "Signaling through transforming G protein-coupled receptors in NIH 3T3 cells involves c-Raf activation. (wikidoc.org)
  • The primary stimulatory processes are considered to be of histaminergic nature via G s -coupled H 2 receptor activation and of cholinergic nature via activation of G q -coupled muscarinic receptors or receptors for gastrin ( 69 ), but other actors are also on the stage. (physiology.org)
  • A1 and A2 adenosine receptor activation inversely modulates potassium currents and membrane potential in DDT1-MF2 smooth muscle cells. (otka-palyazat.hu)
  • In citrated blood, in response to activation of platelets by ADP, collagen, or arachidonic acid, soluble agonists are released from platelet storage granules or generated by platelets (release reaction), which substantially enhances the initial platelet reaction (secondary aggregation). (ahajournals.org)
  • In contrast, in native blood, whether in vivo or in vitro, only activation by α‐thrombin binding to platelet surface glycoprotein Ibα receptors can induce platelet adhesion, dense granule secretion, and aggregation. (ahajournals.org)
  • On the other hand, in the presence of the nucleoside transport inhibitor S-(p-nitrobenzyl)-6-thioninosine (NBTI), adenosine caused a reduction in stimulated histamine release. (uni-wuerzburg.de)
  • The binding of the potent adenosine uptake inhibitor [3H]nitrobenzylthioinosine ([3H]NBI) to brain membrane fractions was investigated. (meta.org)
  • 11. The method according to claim 5 wherein an adenylate kinase inhibitor, which prevents AMP from conversion into adenosine diphosphate (ADP) or adenosine triphosphate (ATP) is administered. (patentsencyclopedia.com)
  • CD73-derived adenosine acts as potent inhibitor of inflammation, and regulatory T cells (Treg) have been shown to express CD73 as a novel marker. (physiology.org)
  • It was originally thought that almost all allergic events were mediated directly only via the high-affinity immunoglobulin E receptors. (frontiersin.org)
  • Outcomes Receptor binding "type":"entrez-nucleotide","attrs":"text":"F13714″,"term_id":"747841″,"term_text":"F13714″F13714 exhibited high affinity for rat hippocampal 5-HT1A receptors and human Baricitinib being 5-HT1A receptors indicated in CHO cells (p K can be.e.m.: 10.010.05 and 10.400.09, respectively, n =3), in keeping with previous findings in rat cortex (Koek et al . (cancer-colorectal.com)
  • The current dogma is that high-affinity protein-protein interactions determine the identity of the G protein with which a particular GPCR interacts and, in turn, dictates the biochemical pathways that are activated by that receptor. (aspetjournals.org)
  • agonist binding to the high affinity state was characterized by a large entropy component compared to the low affinity state. (uni-wuerzburg.de)
  • High affinity agonist binding, however, remained unchanged. (uni-wuerzburg.de)
  • Reversible, saturable, specific, high-affinity binding was demonstrated in both rat and human brain. (meta.org)
  • These findings suggest an important bimodal role of adenosine in regulating histamine release in the human lung. (uni-wuerzburg.de)
  • The receptors showed homogeneaus affinities for antagonists but two affinity states for the agonist (-)-epinephrine, which were modulated by guanine nucleotides. (uni-wuerzburg.de)
  • Co-incubation of equine peripheral blood monocytes with LPS and these agonists resulted in inhibition of TNF-α production with a rank order of potency that strongly correlated with their binding affinities for equine adenosine A 2A receptors. (elsevier.com)
  • Its principal action is adenosine antagonism, and there are a number of caffeine analogs with variable affinities for A1 and A2 receptors [ 2 ]. (hindawi.com)
  • A.sub.2a receptor antagonists in particular are provided to enhance immune responses by reducing T-cell mediated tolerance to antigenic stimuli and agonists are provided to enhance effectiveness of immunosuppressive agents. (patents.com)
  • Both phenomena exploit topographically distinct binding sites to promote unique GPCR conformations that can lead to different patterns of cellular responsiveness. (pnas.org)
  • The adenosine A 1 GPCR (A 1 AR) is a major therapeutic target for cardioprotection, but current agents acting on the receptor are clinically limited for this indication because of on-target bradycardia as a serious adverse effect. (pnas.org)
  • There is also lack of knowledge on the stoichiometry of the participating receptor protomers in GPCR heteroreceptor complexes. (springer.com)
  • The GPCR complexes can also contain ion channel receptors, receptor tyrosine kinases (RTKs), sets of G protein interacting proteins and/or transmitter transporters increasing their integrative capability (Borroto-Escuela et al. (springer.com)
  • The multicomponent modular nature of G protein-coupled receptor (GPCR) systems provides cells with numerous potential combinations by which to transduce signals. (aspetjournals.org)
  • Various GPCR and receptor tyrosine kinases have been localized in caveolae or caveolin-rich cellular fractions along with many of the molecules critical for transducing the signals initiated by these types of receptors: e.g. (aspetjournals.org)
  • This review provides an overview of the medicinal chemistry and therapeutic potential of various agonists/partial agonists, antagonists and allosteric modulators of A1 AR, with a particular emphasis on their current status and future perspectives in clinical settings. (eurekaselect.com)
  • A1 adenosine receptor agonists, antagonists, and allosteric modulators. (eurekaselect.com)
  • Pharmacological agents that act at GPCRs can broadly be categorised into four main classes: agonists, inverse agonists, antagonists and allosteric modulators. (europeanpharmaceuticalreview.com)
  • Because a reduction in A1 expression appears to prevent hypoxia-induced ventriculomegaly and loss of white matter, the pharmacological blockade of A1 may have clinical utility. (wikipedia.org)
  • Overall, the pharmacological characteristics of the human receptors are similar to other species with some species-specific characteristics. (biomedsearch.com)
  • The CHO cells with stably transfected adenosine receptors provide an identical cellular background for such a pharmacological characterization. (biomedsearch.com)
  • It only displays an inhibitory action against PDE2A1 and antagonism at adenosine A(2A) at high concentrations [A31642]. (drugbank.ca)
  • [6] [7] This antagonism of the adenosine receptors, specifically A1 receptors, is responsible for some of the side effects of theophylline like seizures and cardiac arrhythmias. (statpearls.com)
  • It has been shown that an A2AR agonist protects against ischemia-reperfusion injury in porcine allogeneic lung transplantation ( 23 ). (physiology.org)
  • Treatment of stimulated CD4 + T-cells with adenosine (25 μM) potently reduced IFN-γ release which is mediated by adenosine A2a receptors (A2aR). (physiology.org)
  • Four distinct subtypes of P1 receptors have been identified: adenosine A1, A2a, A2b, and A3 receptors (R) which are G protein coupled ( 10 ). (physiology.org)
  • To understand the role of A 2A Rs in the regulation of immune response, we investigated the expression levels of this receptor in different functional lymphocyte subsets. (aspetjournals.org)
  • suggesting a differentiation-dependent regulation of p2x7 receptor expression. (aspetjournals.org)
  • Receptor up-regulation during chronic drug treatment has been proposed to be the mechanism of tolerance to the behavioral stimulant effects of caffeine. (kzeng.info)
  • We propose, therefore, that up-regulation of adenosine receptors may underlie the development of tolerance to the CNS effects of caffeine. (kzeng.info)
  • 1991). However, direct regulation studies outlined below, infusion of the non-selective of postsynaptic processes by amygdala adenosine receptors adenosine receptor agonist 2-chloroadenosine (CADO) has not been examined. (gotomydoctor.com)
  • Although adenosine agonists were shown to attenuate pain behaviors in a variety of animal models, adenosine agonists are also implicated in the regulation of many physiologic processes, especially cardiovascular and neurologic, which either reduce the activity of excitable tissues ( e.g. , by slowing heart rate) or increase the delivery of metabolic substrates ( e.g. , inducing vasodilation). (asahq.org)
  • In addition, adenosine A1 receptor regulation after chronic oral T62 administration was examined. (asahq.org)
  • Adenosine is a purine nucleoside, responsible for the regulation of a wide range of physiological and pathophysiological conditions by binding with four G-protein-coupled receptors (GPCRs), namely A1, A2A, A2B and A3 adenosine receptors (ARs). (eurekaselect.com)
  • This agonist-triggered internalization was reversible for a treatment not exceeding 1 h and became irreversible for prolonged treatment (4 h), leading probably to the degradation and/or down-regulation of the receptor. (aspetjournals.org)
  • and 2) the reduction of the receptor number at the cell surface, either by sequestration (internalization), which involves the receptor endocytosis, or by down-regulation which includes the receptor sequestration and degradation. (aspetjournals.org)
  • Currently, Professor Christie continues to study opioid receptor regulation in pain and analgesia, in particular the processes driving the development of opioid tolerance. (edu.au)
  • Members of this calcium-dependent phospholipid-binding protein family play a role in the regulation of cellular growth and in signal transduction pathways. (cancerindex.org)
  • Consequently, we have investigated the regulation of extracellular nucleotide catabolism by T reg cells that ultimately leads to the generation of pericellular adenosine. (rupress.org)
  • The adenosine receptors play crucial role in the regulation of the function of the myocardium and the central nervous system. (otka-palyazat.hu)
  • Adenosine and sleep-wake regulation. (ke-i.org)
  • Compounds that selectively bind to and activate ADENOSINE A2 RECEPTORS. (nih.gov)
  • that the claimed compounds would have an A1-adenosine receptor antagonistic activity. (epo.org)
  • Binding of [\(^3\)H]NECA to A\(_2\) receptors of rat striatal membranes was inhibited by compounds 2a-d with K\(_i\) values ranging from 2.8 to 16.4 nM. (uni-wuerzburg.de)
  • A 30- to 45-fold selectivity for platelet A\(_2\) receptors compared to A\(_1\) receptors was found for compounds 8a-c in adenylate cyclase studies. (uni-wuerzburg.de)
  • NECA was the most potent agonist with an EC50-value of 2.3 microM whereas all other compounds tested were active at concentrations in the high micromolar range. (biomedsearch.com)
  • Compounds which are able to block adenosine receptors are commonly found in tea, chocolate, and coffee. (kzeng.info)
  • These low molecular weight compounds activated glycogen synthase at ∼100 nmol/l in cultured CHO cells transfected with the insulin receptor and in primary hepatocytes isolated from Sprague-Dawley rats, and at 500 nmol/l in isolated type 1 skeletal muscle of both lean Zucker and ZDF rats. (diabetesjournals.org)
  • 12,13 An adenosine receptor modulator, T62, belonging to a group of thiophene compounds first described a decade ago, 14 has been shown to reduce mechanical allodynia in spinal nerve-injured rats after oral, parenteral, or intrathecal application. (asahq.org)
  • Neurotransmission in the hippocampus is modulated variously through presynaptic metabotropic glutamate receptors (mGluRs). (jneurosci.org)
  • Metabotropic glutamate receptors (mGluRs) have various modulatory functions on neuronal excitability, transmitter release, and synaptic plasticity in the CNS ( Pin and Duvoisin, 1995 ). (jneurosci.org)
  • In this regard, the level of nucleoside adenosine is increased in individuals with obesity. (elsevier.es)
  • the purine nucleoside adenosine is involved in many physiological and pathophysiological events ( 35 ). (physiology.org)
  • In the central nervous system, the nucleoside adenosine regulates neuronal activity by modulating the actions of other neurotransmitter systems, thereby influencing many different physiological processes and behaviors. (ke-i.org)
  • T62 (2-amino-3-(4-chlorobenzoyl)-5,6,7,8-tetrahydrobenzothiophen) is an allosteric adenosine receptor modulator that enhances adenosine binding to the A1 receptor through a conformation change. (asahq.org)
  • Insulin indirectly relieves GS inhibition ( 4 , 5 ) through a signaling cascade beginning with phosphorylation of substrates, including insulin receptor substrate 1 (IRS-1), by the tyrosine kinase activity of activated insulin receptor ( 6 , 7 ). (diabetesjournals.org)
  • These results indicate that regulatory events leading to desensitization, internalization, and recycling in a functional state of hDOR involve phosphorylation by a G protein-coupled receptor kinase, internalization via clathrin-coated vesicles, and dephosphorylation by acid phosphatases. (aspetjournals.org)
  • have shown that desensitization was dependent on the activity of G protein-coupled receptor kinase (GRK) 2, a member of the GRK family. (aspetjournals.org)
  • 1996). "Phosphorylation of human m1 muscarinic acetylcholine receptors by G protein-coupled receptor kinase 2 and protein kinase C. (wikidoc.org)
  • Nomenclature and classification of adenosine receptors-an update. (eurekaselect.com)
  • 2-Alkynyladenosines also exhibited high-affmity binding at solubilized A\(_2\) receptors from human platelet membranes. (uni-wuerzburg.de)
  • Striatal D/sub 1/ receptors and their activity were characterized by (/sup 3/H)SCH23390 binding parameters and D/sub 1/ receptor-stimulated adenylate cyclase activity in striatal membranes. (kzeng.info)
  • Binding studies were performed as described previously in membranes from the brain area or cell line indicated, on the following receptor sites: 5-HT1A in rat hippocampus (Assi and Koek, 1999), h5-HT1A in Chinese hamster ovary (CHO) cells (Newman-Tancredi affinity (pcomparisons were made Baricitinib with the method of contrasts based on the Fisher's statistics (Myers and Well, 1995). (cancer-colorectal.com)
  • This action of barbiturates does not seem to be related to the binding of barbiturates to plasma membranes, as the latter process has different characteristics. (uni-wuerzburg.de)
  • Binding was also decreased by incubation of the membranes in 0.05% Triton X-100 and by treatment with dithiothreitol and iodoacetamide. (meta.org)
  • 2'-MeCCPA is a potent and highly selective agonist at A1 adenosine receptors (Ki values are 3.3, 9580, 37600 and 1150 nM for human recombinant A1, A2A, A2B and A3 receptors respectively), which acts as a full agonist and inhibits forskolin-stimulated adenylyl cyclase activity in rat cortical membranes with an IC50 value of 13.1 nM. (emmx.com)
  • Under normal physiological conditions, adenosine is present in sufficient concentrations to activate A 1 and A 2a receptors. (kzeng.info)
  • The slight stimulatory effect of NBTI alone demonstrates that trapping intracellularly formed adenosine inside mast cells leads to sufficient concentrations of adenosine to stimulate histamine release. (uni-wuerzburg.de)
  • BAY 60-6583 is a potent adenosine A2B receptor agonist that decreases fMLP-induced superoxide production in neutrophils at low concentrations (1-10 nM). (emmx.com)
  • [1] They are named based on the prostanoid to which they preferentially bind and respond, e.g. the receptor responsive to PGI2 at lower concentrations than any other prostanoid is named the Prostacyclin receptor (IP). (wikipedia.org)
  • In early pathological stages of HD and even in symptomatic patients with a grade of 0 on Vonsattelâ s neuropathological severity in HD scale, both D 2 R and A 2A R are significantly and differentially downregulated when compared with D 1 R. 6 These data suggest a selective functional alteration in â ¦ Caffeine hijacks the receptors, artificially controlling your energy levels. (kzeng.info)
  • 100-fold in both radioreceptor binding (K i app = 2.4 nM) and functional assays (EC 50 = 1.6 nM in inhibition of adenylate cyclase) was maintaining a free amino group (secondary) in an amide-linked chain. (biomedcentral.com)
  • Blockade of internalization by agents not interferring with phosphorylation, as hypertonic sucrose or concanavalin A, also blocked the resensitization (receptor functional recovering) process. (aspetjournals.org)
  • The functional role of heteromers of G-protein-coupled receptors is a matter of debate. (jneurosci.org)
  • We conclude that CD39 and CD73 are surface markers of T reg cells that impart a specific biochemical signature characterized by adenosine generation that has functional relevance for cellular immunoregulation. (rupress.org)
  • In this study, we show that A2BR is functional in primary rabbit gastric parietal cells, as indicated by the fact that agonist binding to A2BR increased adenylate cyclase activity and acid production. (physiology.org)
  • Whether adenosine- and A2BR-mediated functional responses play a role in human gastric pathophysiology is yet to be elucidated. (physiology.org)
  • Adenosine Receptors: Structure, Distribution, and Signal Transduction. (eurekaselect.com)
  • Theophylline and caffeine are nonselective adenosine antagonists that are used to stimulate respiration in premature infants. (wikipedia.org)
  • 1 2 3 Pharmacologically, epinephrine is a nonselective adrenergic agonist that can activate both α- andβ -adrenergic receptors. (arvojournals.org)
  • The A3 receptor was characterized utilizing the nonselective agonist [3H]NECA. (biomedsearch.com)
  • To test this hypothesis, we examined the effects of pre- and posttreatment of adenosine and 5′- N -ethylcarboxamidoadenosine (NECA), a nonselective stable AR agonist, on LPS-induced lung injury. (physiology.org)
  • This receptor has an inhibitory function on most of the tissues in which it rests. (wikipedia.org)
  • 5HT1D receptor is a G protein linked receptor that activates an intracellular messenger cascade to produce an inhibitory response by decreasing cellular levels of cAMP. (wikipedia.org)
  • Thus, a stimulatory effect of adenosine was seen in the presence ofXAC, whereas an inhibitory effect was unmasked by NBTI. (uni-wuerzburg.de)
  • The coordinated expression of CD39/CD73 on T reg cells and the adenosine A2A receptor on activated T effector cells generates immunosuppressive loops, indicating roles in the inhibitory function of T reg cells. (rupress.org)
  • The relative potencies of agonists for the A2B adenosine receptor could only be tested by measurement of receptor-stimulated adenylyl cyclase activity. (biomedsearch.com)
  • Because adenosine has such potent effects on inflammation, modulators of adenosine signaling are being evaluated as potential therapeutic options for diseases that have an inflammatory component ( 8 ). (jimmunol.org)
  • There were no differences between brain tissue from control and caffeine-treated rats in number and affinity of adenosine binding sites or in receptor-mediated increasesmore » (A2 adenosine receptor) and decreases (A1 adenosine receptor) in cAMP accumulation. (kzeng.info)
  • Two additional dimensions must be incorporated into our conceptual models: 1) the compartmentation of receptors and effector molecules in subcellular compartments and microdomains of the plasma membrane, and 2) the movement, or translocation, of receptors between cellular compartments (trafficking). (aspetjournals.org)
  • Extra- and/or immediate pericellular accumulation of adenosine elicits immunosuppressive cellular responses that are mediated through several type 1 purinergic (adenosine) receptors, including A2A ( 18 ). (rupress.org)
  • A recent study using mice lacking the equilibrative nucleoside transporter 1, a well-established animal model of alcohol addiction, suggests an expanded role for adenosine in cellular and behavioral circadian timing and alcohol intake, particularly during chronodisruption. (ke-i.org)
  • Methotrexate-induced metabolic changes lead to increased extra-cellular adenosine. (biomedcentral.com)
  • They differ from other 7-TM proteins in their ability to activate guanine-nucleotide binding proteins or β-arrestin and so initiate a signalling cascade. (europeanpharmaceuticalreview.com)
  • A family of heterotrimeric GTP-binding protein alpha subunits that activate PHOSPHOLIPASE C dependent signaling pathways. (labome.org)
  • It was shown to activate the GPR18 receptor, which was postulated to switch macrophages from cytotoxic to reparative. (mdpi.com)
  • NAGly is believed to activate the cannabinoid receptor GPR18 with no affinity for cannabinoid receptor (CB) 1 [ 1 , 2 , 3 ] and transient receptor potential vanilloid 1 (TRPV1) [ 1 ]. (mdpi.com)
  • Accordingly, various soluble agonists are used (adenosine diphosphate [ADP], thromboxane A2 [TXA 2 ], or α‐thrombin) to activate platelets in citrate‐anticoagulated whole blood at very low shear, and the formation of small platelet aggregates (attached to fibrinogen‐coated beads to obtain better optical signals) are measured. (ahajournals.org)
  • Signaling through A 2A adenosine receptors (A 2A R) regulates T lymphocyte expansion and modulates T cell receptor (TCR)-mediated effector functions in vitro. (aspetjournals.org)
  • Subsequent triggering of chemokine receptors through chemokines then activates leukocyte integrins and allows firm adhesion of the cell. (ahajournals.org)
  • TCAs also block histamine-H1 receptors, α1-adrenergic receptors and muscarinic receptors, which accounts for their sedative, hypotensive and anticholinergic effects (e. g. blurred vision, dry mouth, constipation, urinary retention), respectively. (storysteel.gq)
  • Muscarinic receptors mediate many of the effects of acetylcholine in the central and peripheral nervous system. (wikidoc.org)
  • An approach to use multivalent dendrimer carriers for delivery of nucleoside signaling molecules to their cell surface G protein-coupled receptors (GPCRs) was recently introduced. (biomedcentral.com)
  • G protein-coupled receptors (GPCRs) are the largest family of cell surface proteins and tractable drug targets ( 1 , 2 ). (pnas.org)
  • G-protein coupled receptors (GPCRs) are a diverse super-family of proteins located within the plasma membrane of eukaryotic cells which have a common architecture consisting of seven-transmembrane (7-TM) segments, connected by extracellular (ECL) and intracellular (ICL) loops. (europeanpharmaceuticalreview.com)
  • Bath application of 10 to 100 μM phenylephrine, an α 1 adrenergic receptor agonist, significantly increased the frequency of spontaneous excitatory postsynaptic currents in a concentration-dependent manner. (aspetjournals.org)
  • This effect was blocked by the α 1 adrenergic receptor antagonists prazosin or corynanthine. (aspetjournals.org)
  • Furthermore, both α 1 and α 2 adrenergic receptors are present in the PVN ( Cummings and Seybold, 1988 ). (aspetjournals.org)
  • The binding of agonists and antagonists to a2-adrenergic receptors of human platelets was studied. (uni-wuerzburg.de)
  • These multiple physiologic functions controlled by adenosine receptors result in some undesirable side effects from direct adenosine receptor agonists, including headache, nausea, 5 motor weakness, 6,7 chest pain, and atrioventricular block, 8 which limit their clinical application. (asahq.org)
  • An adenosine A 3 receptor agonist (CF-101) is in clinical trials for the treatment of rheumatoid arthritis . (readtiger.com)
  • In sturlies on adenylate cyclase 2',3'-dideoxy-N\(^6\)-cyclohexyladenosine (ddCHA) did not show agonist properties at A\(_1\) or at A\(_2\) receptors. (uni-wuerzburg.de)
  • Binding of Gi1/2/3 causes an inhibition of adenylate cyclase and, therefore, a decrease in the cAMP concentration. (wikipedia.org)
  • Gnx of male rats produced a statistically significant 10% decrease in striatal (/sup 3/H)SCH23390 binding sites with no change in D/sub 1/-stimulated adenylate cyclase activity and no change in striatal(/sup 3/H)sulpiride binding parameters. (kzeng.info)
  • The extracellular site of adenosine formation is generally thought to result from the sequential dephosphorylation of extracellular ATP by action of an ecto-nucleoside triphosphate diphosphohydrolase (CD39) followed by CD73 ( 45 ). (physiology.org)
  • Astrocytic release of adenosine triphosphate and its subsequent extracellular breakdown provides adenosine to drive homeostatic sleep. (ke-i.org)
  • characterization of stably transfected receptors in CHO cells. (biomedsearch.com)
  • We have previously reported ( 14 ) that SDF-1 binds a second receptor, which we assigned the temporary designation of CCX-CKR2 until further characterization was obtained. (rupress.org)
  • However, in altered cardiac function, such as hypoperfusion caused by hypotension, heart attack or cardiac arrest caused by nonperfusing bradycardias, adenosine has a negative effect on physiological functioning by preventing necessary compensatory increases in heart rate and blood pressure that attempt to maintain cerebral perfusion. (wikipedia.org)
  • In particular, A1 AR is ubiquitously present, mediating a variety of physiological processes throughout the body, thus represents a promising drug target for the management of various pathological conditions. (eurekaselect.com)
  • Adenosine-a physiological or pathophysiological agent? (eurekaselect.com)
  • Adenosine A 3 receptors are G protein-coupled receptors that couple to Gi/Gq and are involved in a variety of intracellular signaling pathways and physiological functions. (readtiger.com)