Adenosine
Receptor, Adenosine A2A
Receptor, Adenosine A1
Adenosine A2 Receptor Agonists
Receptor, Adenosine A3
Adenosine Deaminase
Receptor, Adenosine A2B
Receptors, Purinergic P1
Receptors, Adenosine A2
Adenosine Kinase
Adenosine A2 Receptor Antagonists
Adenosine A1 Receptor Antagonists
Serotonin Receptor Agonists
Purinergic P1 Receptor Antagonists
Serotonin 5-HT1 Receptor Agonists
Serotonin 5-HT2 Receptor Agonists
Adenosine-5'-(N-ethylcarboxamide)
Phenethylamines
Dose-Response Relationship, Drug
Adenosine Monophosphate
GABA Agonists
Receptors, Purinergic
Cannabinoid Receptor Agonists
Serotonin 5-HT4 Receptor Agonists
Rats, Sprague-Dawley
Cyclic AMP
Adrenergic alpha-2 Receptor Agonists
Theophylline
Adenosine A3 Receptor Antagonists
2-Chloroadenosine
Receptors, Opioid, kappa
Histamine Agonists
Muscarinic Agonists
Rats, Wistar
Receptors, Opioid, mu
Receptors, Dopamine D2
Serotonin Antagonists
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
Baclofen
Radioligand Assay
5'-Nucleotidase
Nicotinic Agonists
Receptors, Opioid, delta
Receptors, Dopamine D1
Cells, Cultured
Inosine
Guinea Pigs
Calcium
8-Hydroxy-2-(di-n-propylamino)tetralin
Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
Cannabinoids
Adrenergic alpha-1 Receptor Agonists
Tubercidin
Receptors, Opioid
Theobromine
Muscimol
Serotonin
Receptors, Serotonin
Adenosine Triphosphatases
Naphthalenes
Receptors, Purinergic P2
Triazines
Signal Transduction
Purinergic P2Y Receptor Agonists
Dopamine Antagonists
Enkephalin, D-Penicillamine (2,5)-
Isoproterenol
Receptors, Glucagon
Purinergic P2X Receptor Agonists
Receptor, Cannabinoid, CB2
Adenylate Cyclase
Receptor, Cannabinoid, CB1
Neurons
Venoms
Serotonin 5-HT3 Receptor Agonists
Ligands
Drug Interactions
Colforsin
Pyridines
Apomorphine
Sumatriptan
Purines
Indoles
Binding, Competitive
Receptors, Dopamine D3
Enkephalins
Carbachol
Methylhistamines
Dopamine
Dipyridamole
Cricetinae
Receptor, Serotonin, 5-HT1B
Receptors, Serotonin, 5-HT4
Receptors, GABA-B
Benzeneacetamides
Receptors, sigma
Receptors, Prostaglandin E
CHO Cells
Receptor, Serotonin, 5-HT1A
Synaptic Transmission
Receptors, Metabotropic Glutamate
Coformycin
Receptors, Histamine
Receptor, Serotonin, 5-HT2A
Receptors, Dopamine
Receptors, Histamine H3
Enzyme Inhibitors
Clonidine
Receptors, Drug
Norepinephrine
Muscle, Smooth
Histamine
Bicyclo Compounds, Heterocyclic
Disease Models, Animal
Impromidine
Receptor, Serotonin, 5-HT2C
Dopamine Agents
Patch-Clamp Techniques
Rabbits
Guanosine 5'-O-(3-Thiotriphosphate)
Receptors, Histamine H2
Mice, Knockout
Fenoldopam
Naloxone
Uridine Triphosphate
RNA, Messenger
Membrane Potentials
Receptors, G-Protein-Coupled
Amphetamines
Naltrexone
GTP-Binding Proteins
Purinergic P2 Receptor Antagonists
Pentostatin
Receptors, Adrenergic, beta
Dogs
Imidazoles
Cyclic AMP-Dependent Protein Kinases
Receptors, Muscarinic
Corpus Striatum
Thioinosine
Adenosine Phosphosulfate
Microinjections
Structure-Activity Relationship
Microdialysis
Pertussis Toxin
Receptors, Adrenergic, alpha-2
N-Methylaspartate
Substance P
Hippocampus
Rats, Inbred Strains
Phenylephrine
GABA Antagonists
Glutamic Acid
Dronabinol
Receptors, GABA-A
Cyclohexanols
Electrophysiology
Receptors, Serotonin, 5-HT1
Alteration of the purinergic modulation of enteric neurotransmission in the mouse ileum during chronic intestinal inflammation. (1/122)
1. The effect of chronic intestinal inflammation on the purinergic modulation of cholinergic neurotransmission was studied in the mouse ileum. Chronic intestinal inflammation was induced by infection of mice with the parasite Schistosoma mansoni during 16 weeks. 2. S. mansoni infection induced a chronic inflammatory response in the small intestine, which was characterised by intestinal granuloma formation, increased intestinal wall thickness, blunted mucosal villi and an enhanced activity of myeloperoxidase. 3. In control ileum and in chronically inflamed ileum, electrical field stimulation (EFS) of longitudinal muscle strips induced frequency-dependent contractions that were abolished by tetrodotoxin (TTX) and atropine. Carbachol induced dose-dependent contractions that were not affected by TTX but abolished by atropine. 4. In control ileum, adenosine and ATP dose-dependently inhibited the contractions to EFS. Theophylline and 8-phenyltheophylline, P(1) and A(1) receptor antagonists respectively, prevented this inhibitory effect of adenosine and ATP. PPADS, DMPX and MRS 1220, antagonists of P(2), A(2) and A(3) receptors, respectively, did not prevent this inhibitory effect of adenosine and ATP. Adenosine and ATP did not affect the contractions to carbachol. 5. The inhibitory effect of adenosine and ATP on contractions to EFS in control ileum was mimicked by the stable adenosine analogue methyladenosine and by the A(1)-receptor agonist N(6)-cyclohexyladenosine, but not by the A3 receptor agonist 2-Cl IB-MECA or by the ATP analogues alphabeta-methylene-ATP and ADPbetaS. The inhibitory effect of adenosine on contractions to EFS was lost after prolonged (90 min) treatment of control ileum with methyladenosine (100 micro M). 6. In chronically inflamed ileum, adenosine, methyladenosine, N(6)-cyclohexyladenosine and ATP all failed to inhibit the cholinergic nerve-mediated contractions to EFS. Also theophylline, 8-phenyltheophylline, PPADS, DMPX and MRS 1220 had no effect on the contractions to EFS and carbachol. The loss of effect of adenosine and ATP was still evident after 52 weeks of infection. 7. These results indicate that in physiological conditions neuronal adenosine A(1) receptors modulate cholinergic nerve activity in the mouse ileum. However, during chronic intestinal inflammation, this purinergic modulation of cholinergic nerve activity is impaired. This suggests that chronic intestinal inflammation leads to a dysfunction of specific neuronal regulatory mechanisms in the enteric nervous system. (+info)Comparison of effects of MgCl2 and Gpp(NH)p on antagonist and agonist radioligand binding to adenosine A1 receptors. (2/122)
AIM: To investigate modulation of antagonist and agonist binding to adenosine A1 receptors by MgCl2 and 5 -guanylimidodiphosphate (Gpp(NH)p) using rat brain membranes and the A1 antagonist [3H]-8-cyclopentyl-1,3-dipropylxanthine ([3H]DPCPX) and the A1 agonist [3H]-2-chloro-N6-cyclopentyladenosine ([3H]CCPA). METHODS: Parallel saturation and inhibition studies were performed using well-characterised radioligand binding assays and a Brandel Cell Harvester. RESULTS: MgCl2 produced a concentration-dependent decrease (44%), whereas Gpp(NH)p increased [3H]DPCPX binding (19%). In [3H]DPCPX competition studies, agonist affinity was 1.5-14.6-fold higher and 4.6-10-fold lower in the presence of 10 mmol/L MgCl2 and 10 micromol/L Gpp(NH)p respectively; antagonist affinity was unaffected. The decrease in agonist affinity with increasing Gpp(NH)p concentrations was due to a reduction in the proportion of binding to the high affinity receptor state. In contrast to [3H]DPCPX, MgCl2 produced a concentration-dependent increase (72%) and Gpp(NH)p a decrease (85%) in [3H]CCPA binding. Using [3H]CCPA, agonist affinities were 5-17-fold higher than those for [3H]DPCPX, consistent with binding only to the high affinity receptor state. Agonist affinity was 1.3-10.5-fold higher and 2.4-4.7-fold lower on adding MgCl2 or Gpp(NH)p respectively; antagonist affinities were as for [3H]DPCPX. CONCLUSION: The inconsistencies surrounding the effects of MgCl2 and guanine nucleotides on radioligand binding to adenosine A1 receptors were systematically examined. The effects of MgCl2 and Gpp(NH)p on agonist binding to A1 receptors are consistent with their roles in stimulating GTP-hydrolysis at the G-protein alpha-subunit and in blocking formation of the high affinity agonist-receptor-G protein complex. (+info)Involvement of adenosine A1 and A2A receptors in the adenosinergic modulation of the discriminative-stimulus effects of cocaine and methamphetamine in rats. (3/122)
Adenosine, by acting on adenosine A1 and A2A receptors, is known to antagonistically modulate dopaminergic neurotransmission. We have recently reported that nonselective adenosine receptor antagonists (caffeine and 3,7-dimethyl-1-propargylxanthine) can partially substitute for the discriminative-stimulus effects of methamphetamine. In the present study, by using more selective compounds, we investigated the involvement of A1 and A2A receptors in the adenosinergic modulation of the discriminative-stimulus effects of both cocaine and methamphetamine. The effects of the A1 receptor agonist N6-cyclopentyladenosine (CPA; 0.01-0.1 mg/kg) and antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT; 1.3-23.7 mg/kg) and the A2A receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride (CGS 21680; 0.03-0.18 mg/kg) and antagonist 3-(3-hydroxypropyl)-8-(3-methoxystyryl)-7-methyl-1-propargylxanthin phosphate disodium salt (MSX-3; 1-56 mg/kg) were evaluated in rats trained to discriminate either 1 mg/kg methamphetamine or 10 mg/kg cocaine from saline under a fixed-ratio 10 schedule of food presentation. The A1 and A2A receptor antagonists (CPT and MSX-3) both produced high levels of drug-lever selection when substituted for either methamphetamine or cocaine and significantly shifted dose-response curves of both psychostimulants to the left. Unexpectedly, the A2A receptor agonist CGS 21680 also produced drug-appropriate responding (although at lower levels) when substituted for the cocaine-training stimulus, and both CGS 21680 and the A1 receptor agonist CPA significantly shifted the cocaine dose-response curve to the left. In contrast, both agonists did not produce significant levels of drug-lever selection when substituted for the methamphetamine-training stimulus and failed to shift the methamphetamine dose-response curve. Therefore, adenosine A1 and A2A receptors appear to play important but differential roles in the modulation of the discriminative-stimulus effects of methamphetamine and cocaine. (+info)Adenosine A1 receptor agonists block the neuropathological changes in rat retrosplenial cortex after administration of the NMDA receptor antagonist dizocilpine. (4/122)
Noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine ((+)-MK-801) is known to induce neurotoxicity in rat retrosplenial cortex after systemic administration. The present study was undertaken to examine the effects of adenosine A(1) receptor agonists on the neurotoxicity in rat retrosplenial cortex after administration of dizocilpine. Pretreatment with adenosine A(1) receptor agonists, 2-chloro-N(6)-cyclopentyladenosine (CCPA) (0.1, 0.3, 1, or 3 mg/kg, intraperitoneally (i.p.)), or N(6)-cyclopentyladenosine (CPA) (1, 3, or 10 mg/kg, i.p.), attenuated neurotoxicity by dizocilpine (0.5 mg/kg, i.p), in a dose-dependent manner. Coadministration with adenosine A(1) receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX; 3 mg/kg, i.p.) significantly blocked the protective effects of CCPA for dizocilpine-induced neurotoxicity. Furthermore, pretreatment with CCPA (3 mg/kg) attenuated significantly the dizocilpine-induced expression of HSP-70 protein, which is known as a sensitive marker of reversible neuronal damage, and coadministration with DPCPX (3 mg/kg) blocked the inhibitory effects of CCPA for marked expression of HSP-70 protein by administration of dizocilpine. Moreover, pretreatment with CCPA (3 mg/kg, i.p.) significantly suppressed the increase of extracellular acetylcholine (ACh) levels in the retrosplenial cortex by administration of dizocilpine (0.5 mg/kg). In contrast, local perfusion of CCPA (1 microM) into the retrosplenial cortex via the dialysis probe did not alter the ACh levels by administration of dizocilpine (0.5 mg/kg), suggesting that the locus of action of CCPA is not in the retrosplenial cortex. These findings suggest that adenosine A(1) receptors agonists could protect against neuropathological changes in rat retrosplenial cortex after administration of the NMDA receptor antagonist dizocilpine. (+info)Allosteric enhancers of A1 adenosine receptors increase receptor-G protein coupling and counteract Guanine nucleotide effects on agonist binding. (5/122)
Endogenous ligands of G protein-coupled receptors bind to orthosteric sites that are topologically distinct from allosteric sites. Certain aminothiophenes such as (2-amino-4,5-dimethyl-3-thienyl)-[3-(trifluromethyl)-phenyl]-methanone (PD81,723) and 2-amino-4,5,6,7-tetrahydro-benzo[b]thiophen-3-yl)-biphenyl-4-yl-methanone (ATL525) are positive allosteric regulators, or enhancers, of the human A1 adenosine receptor (A1AR). In equilibrium binding assays, 125I-N6-aminobenzyladenosine (125I-ABA) binds to two affinity states of A1AR with KD-high (0.33 microM) and KD-low ( approximately 10 nM). Enhancers have little effect on KD-high but convert all A1AR binding sites to the high-affinity state. Enhancers decrease the potency of guanosine 5'-O-(3-thio)triphosphate (GTPgammaS) as an inhibitor of agonist binding by 100-fold and increase agonist-stimulated guanine nucleotide exchange. The association of 125I-ABA to high-affinity receptors on Chinese hamster ovary (CHO)-hA1 membranes does not follow theoretical single-site association kinetics but is approximated by a bi-exponential equation with t1/2 values of 1.85 and 12.8 min. Allosteric enhancers selectively increase the number of slow binding sites, possibly by stabilizing newly formed receptor-G protein complexes. A new rapid assay method scores enhancer activity on a scale from 0 to 100 based on their ability to prevent the rapid dissociation of 125I-ABA from A1AR in response to GTPgammaS. Compared with PD81,723, ATL525 (100 microM) scores higher (27 versus 79) and has less antagonist activity. ATL525 functionally enhances A1 signaling to inhibit cAMP accumulation in CHO-hA1 cells. These data suggest that simultaneously binding orthosteric and allosteric enhancer ligands convert the A1AR from partly to fully coupled to G proteins and prevents rapid uncoupling upon binding of GTPgammaS. (+info)Role of direct RhoA-phospholipase D1 interaction in mediating adenosine-induced protection from cardiac ischemia. (6/122)
Activation of adenosine A1 or A3 receptors protects heart cells from ischemia-induced injury. The A3 receptor signals via RhoA and phospholipase D (PLD) to induce cardioprotection. The objective of the study was to investigate how RhoA activates PLD to achieve the anti-ischemic effect of adenosine A3 receptors. In an established cardiac myocyte model of preconditioning using the cultured chick embryo heart cells, overexpression of the RhoA-noninteracting PLD1 mutant I870R selectively blocked the A3 agonist (Cl-IBMECA, 10 nM)-induced cardioprotection. I870R caused a significantly higher percentage of cardiac cells killed in A3 agonist-treated than in A1 agonist (CCPA, 10 nM)-treated myocytes (ANOVA and posttest comparison, P<0.01). Consistent with its inhibitory effect on the PLD activity, I870R attenuated the Cl-IBMECA-mediated PLD activation. Cl-IBMECA caused a 41 +/- 15% increase in PLD activity in mock-transfected myocytes (P<0.01, paired t test) while having only a slight stimulatory effect on the PLD activity in I870R-transfected cells. To further test the anti-ischemic role of a direct RhoA-PLD1 interaction, atrial cardiac myocytes were rendered null for native adenosine receptors by treatment with irreversible A1 antagonist m-DITC-XAC and were selectively transfected with the human adenosine A1 or A3 receptor cDNA individually or they were cotransfected with cDNAs encoding either receptor plus I870R. I870R preferentially inhibited the human A3 receptor-mediated protection from ischemia. The RhoA-noninteracting PLD1 mutant caused a significantly higher percentage of cardiac cells killed in myocytes cotransfected with the human A3 receptor than in those cells expressing the human A1 receptor (ANOVA and posttest comparison, P<0.01). The present data provided the first demonstration of a novel physiological role for the direct RhoA-PLD1 interaction, that of potent protection from cardiac ischemia. The study further supported the concept that a divergent signaling mechanism mediates the anti-ischemic effect of adenosine A1 and A3 receptors. (+info)A1 and A2A adenosine receptor modulation of alpha 1-adrenoceptor-mediated contractility in human cultured prostatic stromal cells. (7/122)
1. This study investigated the possibility that adenosine receptors modulate the alpha(1)-adrenoceptor-mediated contractility of human cultured prostatic stromal cells (HCPSC). 2. The nonselective adenosine receptor agonist, 5'-N-ethylcarboxamido-adenosine (NECA; 10 nm-10 microm), and the A(1) adenosine receptor selective agonist, cyclopentyladenosine (CPA; 10 nm-10 microm), elicited significant contractions in HCPSC, with maximum contractile responses of 18+/-3% and 17+/-2% reduction in initial cell length, respectively. 3. In the presence of a threshold concentration of phenylephrine (PE) (100 nm), CPA (1 nm-10 microm) caused contractions, with an EC(50) of 124+/-12 nm and maximum contractile response of 37+/-4%. The A(1) adenosine receptor-selective antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX 100 nm) blocked this effect. In the presence of DPCPX (100 nm), NECA (1 nm-10 microm) inhibited contractions elicited by a submaximal concentration of PE (10 microm), with an IC(50) of 48+/-2 nm. The A(2A) adenosine receptor-selective antagonist 4-(2-[7-amino-2-[furyl][1,2,4]triazolo[2,3-alpha][1,3,5,]triazin-5-yl amino]ethyl)phenol (Zm241385 100 nm) blocked this effect. 4. In BCECF-AM (10 microm)-loaded cells, both CPA (100 pM-1 microm) and NECA (100 pm-10 microm) elicited concentration-dependent decreases in intracellular pH (pH(i)), with EC(50) values of 3.1+/-0.3 and 6.0+/-0.3 nm, respectively. The response to NECA was blocked by Zm241385 (100 nm; apparent pK(B) of 9.4+/-0.4), but not by DPCPX (100 nm). The maximum response to CPA was blocked by DPCPX (100 nm), and unaffected by Zm241385 (100 nm). 5. NECA (10 nm-10 microm) alone did not increase [(3)H]-cAMP in HCPSC. In the presence of DPCPX (100 nm), NECA (10 nm-10 microm) caused a concentration dependent increase in [(3)H]-cAMP, with an EC(50) of 1.2+/-0.1 microm. This response was inhibited by Zm241385 (100 nm). CPA (10 nm-10 microm) had no effect on cAMP, in the presence or absence of forskolin (1 microm). 6. These findings are consistent with a role for adenosine receptors in the modulation of adrenoceptor-mediated contractility in human prostate-derived cells. (+info)A1 adenosine receptor upregulation and activation attenuates neuroinflammation and demyelination in a model of multiple sclerosis. (8/122)
The neuromodulator adenosine regulates immune activation and neuronal survival through specific G-protein-coupled receptors expressed on macrophages and neurons, including the A1 adenosine receptor (A1AR). Here we show that A1AR null (A1AR-/-) mice developed a severe progressive-relapsing form of experimental allergic encephalomyelitis (EAE) compared with their wild-type (A1AR+/+) littermates. Worsened demyelination, axonal injury, and enhanced activation of microglia/macrophages were observed in A1AR-/- animals. In addition, spinal cords from A1AR-/- mice demonstrated increased proinflammatory gene expression during EAE, whereas anti-inflammatory genes were suppressed compared with A1AR+/+ animals. Macrophages from A1AR-/- animals exhibited increased expression of the proinflammatory genes, interleukin-1beta, and matrix metalloproteinase-12 on immune activation when matched with A1AR+/+ control cells. A1AR-/- macrophage-derived soluble factors caused significant oligodendrocyte cytotoxicity compared with wild-type controls. The A1AR was downregulated in microglia in A1AR+/+ mice during EAE accompanied by neuroinflammation, which recapitulated findings in multiple sclerosis (MS) patients. Caffeine treatment augmented A1AR expression on microglia, with ensuing reduction of EAE severity, which was further enhanced by concomitant treatment with the A1AR agonist, adenosine amine congener. Thus, modulation of neuroinflammation by the A1AR represents a novel mechanism that provides new therapeutic opportunities for MS and other demyelinating diseases. (+info)1) They share similarities with humans: Many animal species share similar biological and physiological characteristics with humans, making them useful for studying human diseases. For example, mice and rats are often used to study diseases such as diabetes, heart disease, and cancer because they have similar metabolic and cardiovascular systems to humans.
2) They can be genetically manipulated: Animal disease models can be genetically engineered to develop specific diseases or to model human genetic disorders. This allows researchers to study the progression of the disease and test potential treatments in a controlled environment.
3) They can be used to test drugs and therapies: Before new drugs or therapies are tested in humans, they are often first tested in animal models of disease. This allows researchers to assess the safety and efficacy of the treatment before moving on to human clinical trials.
4) They can provide insights into disease mechanisms: Studying disease models in animals can provide valuable insights into the underlying mechanisms of a particular disease. This information can then be used to develop new treatments or improve existing ones.
5) Reduces the need for human testing: Using animal disease models reduces the need for human testing, which can be time-consuming, expensive, and ethically challenging. However, it is important to note that animal models are not perfect substitutes for human subjects, and results obtained from animal studies may not always translate to humans.
6) They can be used to study infectious diseases: Animal disease models can be used to study infectious diseases such as HIV, TB, and malaria. These models allow researchers to understand how the disease is transmitted, how it progresses, and how it responds to treatment.
7) They can be used to study complex diseases: Animal disease models can be used to study complex diseases such as cancer, diabetes, and heart disease. These models allow researchers to understand the underlying mechanisms of the disease and test potential treatments.
8) They are cost-effective: Animal disease models are often less expensive than human clinical trials, making them a cost-effective way to conduct research.
9) They can be used to study drug delivery: Animal disease models can be used to study drug delivery and pharmacokinetics, which is important for developing new drugs and drug delivery systems.
10) They can be used to study aging: Animal disease models can be used to study the aging process and age-related diseases such as Alzheimer's and Parkinson's. This allows researchers to understand how aging contributes to disease and develop potential treatments.
There are several different types of pain, including:
1. Acute pain: This type of pain is sudden and severe, and it usually lasts for a short period of time. It can be caused by injuries, surgery, or other forms of tissue damage.
2. Chronic pain: This type of pain persists over a long period of time, often lasting more than 3 months. It can be caused by conditions such as arthritis, fibromyalgia, or nerve damage.
3. Neuropathic pain: This type of pain results from damage to the nervous system, and it can be characterized by burning, shooting, or stabbing sensations.
4. Visceral pain: This type of pain originates in the internal organs, and it can be difficult to localize.
5. Psychogenic pain: This type of pain is caused by psychological factors such as stress, anxiety, or depression.
The medical field uses a range of methods to assess and manage pain, including:
1. Pain rating scales: These are numerical scales that patients use to rate the intensity of their pain.
2. Pain diaries: These are records that patients keep to track their pain over time.
3. Clinical interviews: Healthcare providers use these to gather information about the patient's pain experience and other relevant symptoms.
4. Physical examination: This can help healthcare providers identify any underlying causes of pain, such as injuries or inflammation.
5. Imaging studies: These can be used to visualize the body and identify any structural abnormalities that may be contributing to the patient's pain.
6. Medications: There are a wide range of medications available to treat pain, including analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), and muscle relaxants.
7. Alternative therapies: These can include acupuncture, massage, and physical therapy.
8. Interventional procedures: These are minimally invasive procedures that can be used to treat pain, such as nerve blocks and spinal cord stimulation.
It is important for healthcare providers to approach pain management with a multi-modal approach, using a combination of these methods to address the physical, emotional, and social aspects of pain. By doing so, they can help improve the patient's quality of life and reduce their suffering.
It is important to note that catalepsy is not the same as catatonia, which is a more specific condition characterized by a wide range of symptoms, including immobility, mutism, negativism, and emotional dysregulation. However, catalepsy and catatonia do share some similarities, and the terms are often used interchangeably in clinical practice.
The exact cause of catalepsy is not fully understood, but it is thought to be related to dysfunction in certain areas of the brain, such as the neocortex and basal ganglia. In some cases, catalepsy may be a side effect of medication or drug intoxication.
Treatment for catalepsy typically focuses on addressing the underlying cause, such as managing seizures or withdrawing from drugs. In some cases, medications such as benzodiazepines or antipsychotics may be used to help manage symptoms. Other approaches, such as physical therapy and behavioral interventions, may also be helpful in improving mobility and function.
Hyperalgesia is often seen in people with chronic pain conditions, such as fibromyalgia, and it can also be a side effect of certain medications or medical procedures. Treatment options for hyperalgesia depend on the underlying cause of the condition, but may include pain management techniques, physical therapy, and medication adjustments.
In clinical settings, hyperalgesia is often assessed using a pinprick test or other pain tolerance tests to determine the patient's sensitivity to different types of stimuli. The goal of treatment is to reduce the patient's pain and improve their quality of life.
In some cases, hyperemia can be a sign of a more serious underlying condition that requires medical attention. For example, if hyperemia is caused by an inflammatory or infectious process, it may lead to tissue damage or organ dysfunction if left untreated.
Hyperemia can occur in various parts of the body, including the skin, muscles, organs, and other tissues. It is often diagnosed through physical examination and imaging tests such as ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI). Treatment for hyperemia depends on its underlying cause, and may include antibiotics, anti-inflammatory medications, or surgery.
In the context of dermatology, hyperemia is often used to describe a condition called erythema, which is characterized by redness and swelling of the skin due to increased blood flow. Erythema can be caused by various factors, such as sun exposure, allergic reactions, or skin infections. Treatment for erythema may include topical medications, oral medications, or other therapies depending on its underlying cause.
There are several key features of inflammation:
1. Increased blood flow: Blood vessels in the affected area dilate, allowing more blood to flow into the tissue and bringing with it immune cells, nutrients, and other signaling molecules.
2. Leukocyte migration: White blood cells, such as neutrophils and monocytes, migrate towards the site of inflammation in response to chemical signals.
3. Release of mediators: Inflammatory mediators, such as cytokines and chemokines, are released by immune cells and other cells in the affected tissue. These molecules help to coordinate the immune response and attract more immune cells to the site of inflammation.
4. Activation of immune cells: Immune cells, such as macrophages and T cells, become activated and start to phagocytose (engulf) pathogens or damaged tissue.
5. Increased heat production: Inflammation can cause an increase in metabolic activity in the affected tissue, leading to increased heat production.
6. Redness and swelling: Increased blood flow and leakiness of blood vessels can cause redness and swelling in the affected area.
7. Pain: Inflammation can cause pain through the activation of nociceptors (pain-sensing neurons) and the release of pro-inflammatory mediators.
Inflammation can be acute or chronic. Acute inflammation is a short-term response to injury or infection, which helps to resolve the issue quickly. Chronic inflammation is a long-term response that can cause ongoing damage and diseases such as arthritis, asthma, and cancer.
There are several types of inflammation, including:
1. Acute inflammation: A short-term response to injury or infection.
2. Chronic inflammation: A long-term response that can cause ongoing damage and diseases.
3. Autoimmune inflammation: An inappropriate immune response against the body's own tissues.
4. Allergic inflammation: An immune response to a harmless substance, such as pollen or dust mites.
5. Parasitic inflammation: An immune response to parasites, such as worms or fungi.
6. Bacterial inflammation: An immune response to bacteria.
7. Viral inflammation: An immune response to viruses.
8. Fungal inflammation: An immune response to fungi.
There are several ways to reduce inflammation, including:
1. Medications such as nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and disease-modifying anti-rheumatic drugs (DMARDs).
2. Lifestyle changes, such as a healthy diet, regular exercise, stress management, and getting enough sleep.
3. Alternative therapies, such as acupuncture, herbal supplements, and mind-body practices.
4. Addressing underlying conditions, such as hormonal imbalances, gut health issues, and chronic infections.
5. Using anti-inflammatory compounds found in certain foods, such as omega-3 fatty acids, turmeric, and ginger.
It's important to note that chronic inflammation can lead to a range of health problems, including:
1. Arthritis
2. Diabetes
3. Heart disease
4. Cancer
5. Alzheimer's disease
6. Parkinson's disease
7. Autoimmune disorders, such as lupus and rheumatoid arthritis.
Therefore, it's important to manage inflammation effectively to prevent these complications and improve overall health and well-being.
Hypothermia can be mild, moderate, or severe. Mild hypothermia is characterized by shivering and a body temperature of 95 to 97 degrees Fahrenheit (32 to 36.1 degrees Celsius). Moderate hypothermia has a body temperature of 82 to 94 degrees Fahrenheit (28 to 34 degrees Celsius), and the person may appear lethargic, drowsy, or confused. Severe hypothermia is characterized by a body temperature below 82 degrees Fahrenheit (28 degrees Celsius) and can lead to coma and even death if not treated promptly.
Treatment for hypothermia typically involves warming the person up slowly, using blankets or heating pads, and providing warm fluids to drink. In severe cases, medical professionals may use a specialized warm water bath or apply warm packs to specific areas of the body.
Preventing hypothermia is important, especially in cold weather conditions. This can be done by dressing appropriately for the weather, staying dry and avoiding wet clothing, eating regularly to maintain energy levels, and seeking shelter if you become stranded or lost. It's also essential to recognize the signs of hypothermia early on so that treatment can begin promptly.
There are different types of anoxia, including:
1. Cerebral anoxia: This occurs when the brain does not receive enough oxygen, leading to cognitive impairment, confusion, and loss of consciousness.
2. Pulmonary anoxia: This occurs when the lungs do not receive enough oxygen, leading to shortness of breath, coughing, and chest pain.
3. Cardiac anoxia: This occurs when the heart does not receive enough oxygen, leading to cardiac arrest and potentially death.
4. Global anoxia: This is a complete lack of oxygen to the entire body, leading to widespread tissue damage and death.
Treatment for anoxia depends on the underlying cause and the severity of the condition. In some cases, hospitalization may be necessary to provide oxygen therapy, pain management, and other supportive care. In severe cases, anoxia can lead to long-term disability or death.
Prevention of anoxia is important, and this includes managing underlying medical conditions such as heart disease, diabetes, and respiratory problems. It also involves avoiding activities that can lead to oxygen deprivation, such as scuba diving or high-altitude climbing, without proper training and equipment.
In summary, anoxia is a serious medical condition that occurs when there is a lack of oxygen in the body or specific tissues or organs. It can cause cell death and tissue damage, leading to serious health complications and even death if left untreated. Early diagnosis and treatment are crucial to prevent long-term disability or death.
* Anxiety
* Depression
* Fatigue
* Insomnia
* Muscle and bone pain
* Nausea and vomiting
* Seizures (in severe cases)
* Sweating
* Tremors
The specific symptoms of substance withdrawal syndrome can vary depending on the substance being withdrawn from, but some common symptoms include:
* Alcohol: tremors, anxiety, insomnia, nausea and vomiting, headaches, and seizures
* Opioids: withdrawal symptoms can include anxiety, muscle aches, sweating, nausea and vomiting, diarrhea, and depression
* Benzodiazepines: withdrawal symptoms can include anxiety, insomnia, tremors, and seizures
The diagnosis of substance withdrawal syndrome is typically made based on the patient's history of substance use and the presence of withdrawal symptoms. A healthcare provider may also order laboratory tests to rule out other conditions that may be causing the symptoms. Treatment for substance withdrawal syndrome usually involves supportive care, such as rest, hydration, and pain management, as well as medication to manage withdrawal symptoms. In some cases, medical professionals may also recommend a gradual tapering of the substance over a period of time to minimize withdrawal symptoms.
It is important for individuals who are experiencing withdrawal symptoms to seek medical attention as soon as possible, as untreated withdrawal can lead to serious complications, such as seizures and dehydration. With appropriate treatment, most individuals with substance withdrawal syndrome can recover fully and successfully overcome their addiction.
Dyskinesias can be caused by a variety of drugs, including:
1. Antipsychotic medications: These drugs are commonly used to treat conditions such as schizophrenia and bipolar disorder.
2. Antidepressant medications: Certain antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), can cause dyskinesias.
3. Anti-anxiety medications: Benzodiazepines can cause dyskinesias, especially at high doses or with long-term use.
4. Opioids: These drugs can cause dyskinesias as a side effect, particularly when taken in high doses or for prolonged periods.
5. Antihistamines: Some antihistamines can cause dyskinesias, especially in older adults.
6. Anticonvulsants: Certain anticonvulsant medications, such as valproate and carbamazepine, can cause dyskinesias.
7. Corticosteroids: Long-term use of corticosteroids can lead to dyskinesias, especially in the face and limbs.
The symptoms of drug-induced dyskinesias can vary depending on the type of medication being taken and the individual's response to it. Common symptoms include:
1. Involuntary movements of the face, arms, legs, or trunk
2. Jerky or twitching movements
3. Tremors or shaking
4. Slow, rigid movements
5. Lack of coordination and balance
6. Difficulty with speech and swallowing
7. Fatigue and weakness
If you are experiencing dyskinesias as a result of medication, it is important to speak with your healthcare provider. They may be able to adjust your medication regimen or recommend alternative treatments to help manage the symptoms. In some cases, discontinuing the medication that is causing the dyskinesias may be necessary. Additionally, your healthcare provider may recommend other therapies, such as physical therapy or speech therapy, to help improve your mobility and communication skills.
MRI can occur in various cardiovascular conditions, such as myocardial infarction (heart attack), cardiac arrest, and cardiac surgery. The severity of MRI can range from mild to severe, depending on the extent and duration of the ischemic event.
The pathophysiology of MRI involves a complex interplay of various cellular and molecular mechanisms. During ischemia, the heart muscle cells undergo changes in energy metabolism, electrolyte balance, and cell membrane function. When blood flow is restored, these changes can lead to an influx of calcium ions into the cells, activation of enzymes, and production of reactive oxygen species (ROS), which can damage the cells and their membranes.
The clinical presentation of MRI can vary depending on the severity of the injury. Some patients may experience chest pain, shortness of breath, and fatigue. Others may have more severe symptoms, such as cardiogenic shock or ventricular arrhythmias. The diagnosis of MRI is based on a combination of clinical findings, electrocardiography (ECG), echocardiography, and cardiac biomarkers.
The treatment of MRI is focused on addressing the underlying cause of the injury and managing its symptoms. For example, in patients with myocardial infarction, thrombolysis or percutaneous coronary intervention may be used to restore blood flow to the affected area. In patients with cardiac arrest, cardiopulmonary resuscitation (CPR) and other life-saving interventions may be necessary.
Prevention of MRI is crucial in reducing its incidence and severity. This involves aggressive risk factor management, such as controlling hypertension, diabetes, and dyslipidemia, as well as smoking cessation and stress reduction. Additionally, patients with a history of MI should adhere to their medication regimen, which may include beta blockers, ACE inhibitors or ARBs, statins, and aspirin.
In conclusion, myocardial injury with ST-segment elevation (MRI) is a life-threatening condition that requires prompt recognition and treatment. While the clinical presentation can vary depending on the severity of the injury, early diagnosis and management are crucial in reducing morbidity and mortality. Prevention through aggressive risk factor management and adherence to medication regimens is also essential in preventing MRI.
Myocardial ischemia can be caused by a variety of factors, including coronary artery disease, high blood pressure, diabetes, and smoking. It can also be triggered by physical exertion or stress.
There are several types of myocardial ischemia, including:
1. Stable angina: This is the most common type of myocardial ischemia, and it is characterized by a predictable pattern of chest pain that occurs during physical activity or emotional stress.
2. Unstable angina: This is a more severe type of myocardial ischemia that can occur without any identifiable trigger, and can be accompanied by other symptoms such as shortness of breath or vomiting.
3. Acute coronary syndrome (ACS): This is a condition that includes both stable angina and unstable angina, and it is characterized by a sudden reduction in blood flow to the heart muscle.
4. Heart attack (myocardial infarction): This is a type of myocardial ischemia that occurs when the blood flow to the heart muscle is completely blocked, resulting in damage or death of the cardiac tissue.
Myocardial ischemia can be diagnosed through a variety of tests, including electrocardiograms (ECGs), stress tests, and imaging studies such as echocardiography or cardiac magnetic resonance imaging (MRI). Treatment options for myocardial ischemia include medications such as nitrates, beta blockers, and calcium channel blockers, as well as lifestyle changes such as quitting smoking, losing weight, and exercising regularly. In severe cases, surgical procedures such as coronary artery bypass grafting or angioplasty may be necessary.
There are many different types of seizures, each with its own unique set of symptoms. Some common types of seizures include:
1. Generalized seizures: These seizures affect both sides of the brain and can cause a range of symptoms, including convulsions, loss of consciousness, and muscle stiffness.
2. Focal seizures: These seizures affect only one part of the brain and can cause more specific symptoms, such as weakness or numbness in a limb, or changes in sensation or vision.
3. Tonic-clonic seizures: These seizures are also known as grand mal seizures and can cause convulsions, loss of consciousness, and muscle stiffness.
4. Absence seizures: These seizures are also known as petit mal seizures and can cause a brief loss of consciousness or staring spell.
5. Myoclonic seizures: These seizures can cause sudden, brief muscle jerks or twitches.
6. Atonic seizures: These seizures can cause a sudden loss of muscle tone, which can lead to falls or drops.
7. Lennox-Gastaut syndrome: This is a rare and severe form of epilepsy that can cause multiple types of seizures, including tonic, atonic, and myoclonic seizures.
Seizures can be diagnosed through a combination of medical history, physical examination, and diagnostic tests such as electroencephalography (EEG) or imaging studies. Treatment for seizures usually involves anticonvulsant medications, but in some cases, surgery or other interventions may be necessary.
Overall, seizures are a complex and multifaceted symptom that can have a significant impact on an individual's quality of life. It is important to seek medical attention if you or someone you know is experiencing seizures, as early diagnosis and treatment can help to improve outcomes and reduce the risk of complications.
Hyperkinesis can manifest in different ways, including:
1. Excessive movement or restlessness: This can include fidgeting, pacing, or other forms of constant motion.
2. Involuntary movements: These can include tremors, tics, or other sudden, uncontrolled movements.
3. Overactive behavior: This can include rapid speaking, excessive talking, or other behaviors that are not typical for the individual.
4. Difficulty sitting still or remaining quiet: This can be due to an inability to focus or a sense of inner restlessness or agitation.
5. Increased energy levels: This can result in excessive physical activity, such as running, jumping, or other forms of high-energy behavior.
Hyperkinesis can have a significant impact on daily life, making it difficult to focus, complete tasks, and maintain relationships. It is important to seek medical attention if symptoms persist or worsen over time, as hyperkinesis can be a sign of an underlying neurological or psychiatric condition that requires treatment.
Reperfusion injury can cause inflammation, cell death, and impaired function in the affected tissue or organ. The severity of reperfusion injury can vary depending on the duration and severity of the initial ischemic event, as well as the promptness and effectiveness of treatment to restore blood flow.
Reperfusion injury can be a complicating factor in various medical conditions, including:
1. Myocardial infarction (heart attack): Reperfusion injury can occur when blood flow is restored to the heart muscle after a heart attack, leading to inflammation and cell death.
2. Stroke: Reperfusion injury can occur when blood flow is restored to the brain after an ischemic stroke, leading to inflammation and damage to brain tissue.
3. Organ transplantation: Reperfusion injury can occur when a transplanted organ is subjected to ischemia during harvesting or preservation, and then reperfused with blood.
4. Peripheral arterial disease: Reperfusion injury can occur when blood flow is restored to a previously occluded peripheral artery, leading to inflammation and damage to the affected tissue.
Treatment of reperfusion injury often involves medications to reduce inflammation and oxidative stress, as well as supportive care to manage symptoms and prevent further complications. In some cases, experimental therapies such as stem cell transplantation or gene therapy may be used to promote tissue repair and regeneration.
Body weight is an important health indicator, as it can affect an individual's risk for certain medical conditions, such as obesity, diabetes, and cardiovascular disease. Maintaining a healthy body weight is essential for overall health and well-being, and there are many ways to do so, including a balanced diet, regular exercise, and other lifestyle changes.
There are several ways to measure body weight, including:
1. Scale: This is the most common method of measuring body weight, and it involves standing on a scale that displays the individual's weight in kg or lb.
2. Body fat calipers: These are used to measure body fat percentage by pinching the skin at specific points on the body.
3. Skinfold measurements: This method involves measuring the thickness of the skin folds at specific points on the body to estimate body fat percentage.
4. Bioelectrical impedance analysis (BIA): This is a non-invasive method that uses electrical impulses to measure body fat percentage.
5. Dual-energy X-ray absorptiometry (DXA): This is a more accurate method of measuring body composition, including bone density and body fat percentage.
It's important to note that body weight can fluctuate throughout the day due to factors such as water retention, so it's best to measure body weight at the same time each day for the most accurate results. Additionally, it's important to use a reliable scale or measuring tool to ensure accurate measurements.
Adenosine
N6-Cyclopentyladenosine
Dipropylcyclopentylxanthine
Adenosine receptor
CCPA (biochemistry)
Valerian (herb)
Adenosine A1 receptor
Pre-Bötzinger complex
Caffeine-induced anxiety disorder
Adenosine A2A receptor
PSB-10
Dopamine receptor D1
Minoxidil
Adenosine A2B receptor
Pharmacodynamics
5-HT2A receptor
5-HT1D receptor
Adenosine A3 receptor
Gliotransmitter
Dopamine receptor
Arthur Christopoulos
Caffeine
Adenosine A2A receptor antagonist
Paraxanthine
Basal ganglia
Purinergic signalling
Heteroreceptor
Orexin
Niacin
Molecular and epigenetic mechanisms of alcoholism
Nucleus accumbens
Brown adipose tissue
G protein-coupled receptor
Nicotinic acid adenine dinucleotide phosphate
Bafilomycin
Preclinical Evaluation of the First Adenosine A1 Receptor Partial Agonist Radioligand for Positron Emission Tomography Imaging ...
Regulated hypothermia in mouse is caused by AMP, adenosine A1 and A3 receptor agonists via three distinct mechanisms | NIH...
MEDLINE Data Changes 2011: Revised Entry Combinations Table. NLM Technical Bulletin. 2010 Nov-Dec
New fluorescent adenosine A1-receptor agonists that allow quantification of ligand-receptor interactions in microdomains of...
The effect of GR190178, a selective low-efficacy adenosine A1 receptor agonist, on the treatment of neuropathic hyperalgesia in...
Evaluation of carbon-11 labeled KF15372 and its ethyl and methyl derivatives as a potential CNS adenosine A1 receptor ligand -...
Adenosine receptor agonists, partial agonists, and antagonists (U.S. Patent Number 13/479,973) - NIDDK
Biomarkers Search
RFA-AA-08-010: Alcohol Tolerance: Contribution to Consumption (R21)
MeSH Browser
Publication Detail
Papers: 14 Mar 2020 - 20 Mar 2020 Archives - International Association for the Study of Pain (IASP)
PT - JOURNAL ARTICLE
Characterization of the binding of a novel nonxanthine adenosine antagonist radioligand, [3H]CGS 15943, to multiple affinity...
Oxidosqualene-lanosterol cyclase inhibitor
DeCS
MeSH Browser
Adenosine Signaling through A1 Receptors Inhibits Chemosensitive Neurons in the Retrotrapezoid Nucleus | eNeuro
Pesquisa | Prevenção e Controle de Câncer
GPCR Archives - Innoprot
Clinical Hemorheology and Microcirculation - Volume 59, issue 3 - Journals - IOS Press
Adenosine Reduces Glutamate Release in Rat Spinal Synaptosomes | Anesthesiology | American Society of Anesthesiologists
GPCR/G protein - Signaling Pathways
Search results | TNO Publications
ATL 313, A Selective A Adenosine Receptor Agonist, Reduces Myocardial Infarct Size in a Rat Ischemia/Reperfusion Model
Arama Sonuçları | AXSIS
Kenneth A. Jacobson, Ph.D. | Principal Investigators | NIH Intramural Research Program
Therapeutics | Technology Transfer
Antagonist13
- The uptake of each compound was decreased by carrier KF15372, but not by an A2A antagonist, indicating the selective affinity for the A1 receptors. (nih.gov)
- Synthesis and preliminary evaluation of [11C]KF15372, a selective adenosine A1 antagonist. (nih.gov)
- 2. The role of CGRP receptor antagonist (CGRP8-37) and Endomorphin-1 combination therapy on neuropathic pain alleviation and expression of Sigma-1 receptors and antioxidants in rats. (nih.gov)
- Characterization of the binding of a novel nonxanthine adenosine antagonist radioligand, [3H]CGS 15943, to multiple affinity states of the adenosine A1 receptor in the rat cortex. (aspetjournals.org)
- The triazoloquinazoline CGS 15943 is the first reported nonxanthine adenosine antagonist that has high affinity for brain adenosine receptors. (aspetjournals.org)
- Agonist competition curves generated in the presence of 1 mM GTP resulted in a rightward shift and steepening of the inhibition-concentration curves, whereas antagonist binding was not altered in the presence of GTP. (aspetjournals.org)
- Next, using a newly developed coculture system of isolated myenteric neurons and mucosal-type bone-marrow-derived mast cells (mBMMCs) with a calcium imaging system, we demonstrated that the stimulation of isolated myenteric neurons by veratridine caused the activation of mBMMCs, which was suppressed by the adenosine A3 receptor antagonist MRE 3008F20. (bvsalud.org)
- 14)Characterization of peptide 20-30 of follicle stimulating hormone receptor as an antagonist of receptor activity: significance of charged residues. (edu.in)
- Blockade of capsaicin-evoked glutamate release by adenosine was reversed similarly in synaptosomes from normal and spinal nerve-ligated animals by an A1 adenosine receptor antagonist DPCPX (8-cyclopentyl-1,3-dipropylxanthine) but not by an A2 adenosine receptor antagonist DMPX (3'7-dimethyl-1-proparaglyxanthine). (asahq.org)
- GC62708 σ1 Receptor antagonist-1 σ1 수용체 길항제-1은 매우 강력하고 선택적인 시그마 1 수용체 길항제입니다(pKi=10.28). (glpbio.com)
- GC41668 (±)-Clopidogrel (hydrochloride) Clopidogrel is an antithrombic compound whose active metabolite is a selective, irreversible antagonist of the platelet purinergic P2Y12 receptor (IC50 = 100 nM). (glpbio.com)
- N-ethylcarboxamidoadenosine (NECA) (non-selective A1 /A2 agonist, 0.1 mg/kg, i.v.)-treated I/R, and theophylline (non-selective A1 /A2 antagonist, 20 mg/kg, i.v.)-treated I/R groups. (beun.edu.tr)
- A 2a receptor antagonist), or dimethyl sulfoxide (DMSO) administrations. (ijp-online.com)
Antagonists9
- The potency order for adenosine antagonists was CGS 15943 (IC50 = 5 nM) greater than 8-phenyltheophylline greater than 1,3-dipropyl-8-(4-amino-2-chloro)phenylxanthine greater than 1,3-diethyl-8-phenylxanthine greater than theophylline = caffeine (IC50 greater than 10,000 nM). (aspetjournals.org)
- This work may also have clinical relevance since A1 receptor antagonists like caffeine are used to treat respiratory problems in premature infancy. (eneuro.org)
- Adenosine with or without adenosine A1 and A2 receptor antagonists was applied to determine the efficacy and mechanism of adenosine to reduce capsaicin-evoked glutamate release. (asahq.org)
- 6-9 Peripheral noxious stimulation increases the release of glutamate from the rat dorsal spinal cord in vivo , 10 whereas pharmacologic and electrophysiologic studies indicate that glutamate receptor antagonists produce antinociceptive effects in rodents and humans. (asahq.org)
- Our overall goals are to design, chemically synthesize, and characterize pharmacologically new agonists and antagonists for the four subtypes of adenosine receptors (ARs) and eight subtypes of P2Y receptors and to explore their potential for treating human disease conditions. (nih.gov)
- I am a medicinal chemist with interests in the structure and pharmacology of receptors and in developing drugs that act as agonists or antagonists of G protein-coupled receptors (GPCRs). (nih.gov)
- Recent accomplishments include the design and synthesis of the highly potent and selective A3 adenosine receptor agonists and antagonists, using a combination of library screening and optimization of known adenosine receptor ligands. (nih.gov)
- We have synthesized the first P2Y1 receptor-selective antagonists through functionalization of adenine nucleotides. (nih.gov)
- The antagonists were optimized with the aid of receptor homology modeling. (nih.gov)
Ligands8
- To address the emerging need for fluorescently labeled ligands to support these technologies, we have developed a series of red-emitting agonists for the human adenosine A 1 -receptor that, collectively, are N 6 -aminoalkyl derivatives of adenosine or adenosine 5′-N-ethyl carboxamide. (nottingham.edu.cn)
- These results show that three compounds have potential as PET ligands for CNS adenosine A1 receptors. (nih.gov)
- The opioid system of mu, delta and kappa receptors (MOR, DOR, KOR) and their peptide ligands (β-endorphin, enkephalin, dynorphin) have complex and partially opposing effects on amygdala function. (iasp-pain.org)
- 26)New ligands for melanocortin receptors. (edu.in)
- Novel ligands (small molecules) for these receptors are developed using classical synthetic approaches and also by semirational methods based on molecular modeling and template design. (nih.gov)
- 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)
High affinity3
- We report the presence of functional high-affinity IgE receptors (FcεRIs) in enteric neurons. (bvsalud.org)
- Fluorescence Correlation Spectroscopy (FCS) studies with a fluorescent agonist (ABEA-X-BY630) demonstrated that both wild-type and mutant receptors bind agonist with high affinity but in subsequent downstream signaling assays the R108A mutation abolished agonist-mediated inhibition of cAMP production and ERK phosphorylation. (bvsalud.org)
- This technology relates to a group of compounds that display high affinity and specificity for the A1 adenosine receptor subtype. (nih.gov)
Neuropathic8
- The effect of GR190178, a selective low-efficacy adenosine A1 receptor agonist, on the treatment of neuropathic hyperalgesia in the rat. (ox.ac.uk)
- 14. Activation of spinal and supraspinal cannabinoid-1 receptors leads to antinociception in a rat model of neuropathic spinal cord injury pain. (nih.gov)
- Treatment of chronic neuropathic pain: purine receptor modulation. (iasp-pain.org)
- A3 adenosine receptor (A3AR) agonists have emerged as potent relievers of neuropathic pain by a T cell-mediated production of IL-10. (bvsalud.org)
- 4,5 The primary aim of the current study was to determine whether adenosine-mediated inhibition of spinal glutamate release was increased in an animal model of neuropathic pain, potentially providing an explanation for this selective effect of intrathecal adenosine in hypersensitive states. (asahq.org)
- We recently published in collaboration with Daniela Salvemini of St. Louis University the protective effect of A3 agonists in animal models of neuropathic pain. (nih.gov)
- We have discovered highly specific A3 agonists that reduce neuropathic pain in the mouse and rat and prevent its development. (nih.gov)
- This technology includes the creation and use of A3 adenosine receptor (A3AR)-selective agonists for treating chemotherapy-induced peripheral neuropathy, chronic neuropathic pain, rheumatoid arthritis, psoriasis, and other conditions. (nih.gov)
Affinity5
- The complex binding interactions found with adenosine agonists indicate that [3H]CGS 15943 labels both high and low affinity components of the adenosine A1 receptor in the rat cortex. (aspetjournals.org)
- Additionally, the present data also provide some evidence that [3H]CGS 15943 may also recognize an additional low affinity binding component, which may represent a putative low affinity A2b receptor in this tissue. (aspetjournals.org)
- The binding affinity of D1 receptors is 10 to 100-fold lower than D2 receptors. (brainmatrix.com)
- The difference in affinity takes on significance as different temporal patterns of release and relative extracellular concentration of dopamine engage differently with D1 or D2 receptors. (brainmatrix.com)
- [6] With their lower-affinity, D1 receptors are considered to activate in response to phasic dopamine signals in the micromolar range, whereas higher-affinity, D2 receptors respond to nanomolar, tonic levels. (brainmatrix.com)
Protein-Coupled Receptor3
- 15)Cross-Linking of a DOPA-Containing Peptide Ligand into its G Protein-Coupled Receptor. (edu.in)
- Dopamine receptors belong to the 7 transmembrane, G protein-coupled receptor family (GPCRs). (brainmatrix.com)
- The receptors belong to and are structurally homologous to the G-protein coupled receptor (GPCR) superfamily, and contain the requisite seven-transmembrane domains. (brainmatrix.com)
Ligand4
- Fluorescence spectroscopy is becoming a valuable addition to the array of techniques available for scrutinizing ligand-receptor interactions in biological systems. (nottingham.edu.cn)
- Visualization and confirmation of ligand-receptor interactions at the cell membrane were accomplished using confocal microscopy, and their suitability for use in FCS was demonstrated by quantification of agonist binding in small areas of cell membrane. (nottingham.edu.cn)
- Advanced microscopy techniques have shown that these receptors can be localized to discrete microdomains and reorganization upon ligand activation is crucial in orchestrating their signaling. (bvsalud.org)
- Receptors are computer-modeled by homology to GPCRs of known structure, and the models for ligand recognition are tested and refined using site-directed mutagenesis of the receptor proteins. (nih.gov)
Effects of adenosine2
- The goal of this study was to characterize effects of adenosine on chemosensitive RTN neurons and identify intrinsic and synaptic mechanisms underlying this response. (eneuro.org)
- The aim of the present study was to examine the effects of adenosine A1 /A2 receptor activation on reperfusion-induced small intestinal injury in rat. (beun.edu.tr)
Characterization1
- PMID- 214398 TI - Characterization of an adenosine triphosphatase of the avian myeloblastosis virus and the virus-infected myeloblast. (nih.gov)
Study was to characterize2
- The objective of the present study was to characterize the effects of the full agonist N6-cyclopentyladenosine (CPA) and its. (tno.nl)
- The objective of this study was to characterize the effects of the adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) and its low efficacy derivatives 2′-deoxy-CPA (2DCPA), 3′-deoxy-CPA (3DCPA), 8-ethylamino-CPA (8ECPA) and 8-butylamino-CPA (8BCPA) on the release of acetylcholine (ACh) using intrastriatal microdialysis. (tno.nl)
Endogenous5
- A3 receptors for adenosine are found in most cells and endogenous activation of the A3 receptors can result in apoptosis, thereby relieving the inflammation or targeting a tumor. (nih.gov)
- Adenosine is an endogenous nucleoside that shows its well-known cardiovascular effects by A 1 , A 2a , and A 2b receptors. (ijp-online.com)
- Some studies have shown that adenosine A 1 receptor stimulation and/or endogenous adenosine may have a role in amitriptyline-a tricyclic antidepressant (TCA)-induced cardiovascular toxicity such as hypotension, QRS, and QT prolongation. (ijp-online.com)
- Therefore, aim of this study is to clarify the role of adenosine receptors and/or endogenous adenosine in the mechanism of the cardiovascular toxic effects induced by citalopram overdose in rats. (ijp-online.com)
- The indole moiety is related to the neurotransmitter serotonin which is widely implicated for brain function and cognition as the endogenous receptor agonist. (frontiersin.org)
Selective A1 adenosin1
- NIDDK announces the availability of a highly selective A1 adenosine receptor (AR) agonist. (nih.gov)
A3AR5
- However, AMP-induced torpor was intact in mice lacking any one of the adenosine receptors (A1AR, A2AAR, A2BAR, or A3AR). (nih.gov)
- Our lab has characterized a third mechanism to achieve hypothermia through A3AR mast cell degranulation and central histamine H1 receptors. (nih.gov)
- We found that putative A1AR agonists at commonly used doses are non-selective and work via both A1AR and A3AR to cause hypothermia. (nih.gov)
- Finally, we show the torpor response after a 24 hour fast occurs in mice lacking A1AR, A3AR, or both, demonstrating that these receptors are not required for this effect. (nih.gov)
- In the mouse model of Chronic Constriction Injury (CCI), the acute intraperitoneal co-administration of the A3AR agonist IB-MECA (0.5 mg/kg) and the H4R agonist VUF 8430 (10 mg/kg), were additive in counteracting mechano-allodynia increasing IL-10 plasma levels. (bvsalud.org)
Subtypes4
- Four different adenosine receptor subtypes have been defined. (asahq.org)
- There are five receptor subtypes, D1-D5, distinguished by the different second messengers they couple to. (brainmatrix.com)
- D1 and D5 form the stimulatory D1-like dopamine receptor family, and D2, D3, and D4 receptor subtypes the inhibitory D2-like family of receptors. (brainmatrix.com)
- This has recently been called into question under models of normal physiological conditions, taking into account the kinetics of and relative abundance of the two, and showing both receptor subtypes respond equally to either phasic or tonic scenarios owing fundamentally to their slower unbinding of dopamine. (brainmatrix.com)
Inhibition4
- In AL rats, inhibition of ISO-stimulated adenylyl cyclase by the AdoA1R agonist, N6-p-sulfophenyladenosine (SPA) decreased with age. (aspetjournals.org)
- Here, the authors test whether increased inhibition by adenosine of glutamate release from afferents after injury accounts for this difference. (asahq.org)
- Capsaicin-evoked glutamate release, as well as its inhibition by adenosine, did not differ between synaptosomes prepared from tissue ipsilateral and contralateral to spinal nerve ligation. (asahq.org)
- [11] It was observed that the negative inotropic and chronotropic effects induced by citalopram can be explained by the inhibition of re-uptake of adenosine or the activation of adenosine A 1 receptors. (ijp-online.com)
Inhibits5
- Recent evidence suggests adenosine inhibits RTN chemoreception in vivo by activation of A1 receptors. (eneuro.org)
- Cell-attached recordings from RTN chemoreceptors in slices from rat or wild-type mouse pups (mixed sex) show that exposure to adenosine (1 µM) inhibits chemoreceptor activity by an A1 receptor-dependent mechanism. (eneuro.org)
- These results show that adenosine activation of A1 receptors inhibits chemosensitive RTN neurons by direct activation of a G-protein-regulated inward-rectifier K + (GIRK)-like conductance, and presynaptically, by suppression of excitatory synaptic input to chemoreceptors. (eneuro.org)
- Here, we show that adenosine activation of A1 receptors inhibits RTN neurons by activation of an inward rectifying K + conductance, and by selective suppression of excitatory synaptic input to chemoreceptors. (eneuro.org)
- These observations confirm previous neurophysiologic studies that presynaptic adenosine A1 receptor activation inhibits glutamate release from primary afferents. (asahq.org)
Full agonist1
- The A1AR-selective full agonist MRS5474 displayed anticonvulsant activity in vivo in a model of minimal clonic seizures, without toxicity characteristic of other A1AR agonists. (nih.gov)
Activation12
- Adenosine A1 receptor activation increases myocardial protein S-nitrosothiols and elicits protection from ischemia-reperfusion injury in male and female hearts. (nih.gov)
- 30 nM) alone did not potentiate CO 2 /H + -stimulated activity, suggesting activation of A1 receptors does not limit chemoreceptor activity under these reduced conditions. (eneuro.org)
- The H4 histamine receptor (H4R), also implicated in pain modulation, is expressed on T cells playing a preeminent role in its activation and release of IL-10. (bvsalud.org)
- cAMP NOMAD ADORA1 Cell Line allows to assay compounds analyzing the G-Protein signalling pathway by Go involving receptor activation. (innoprot.com)
- 21)Protection conferred by Corticotropin-releasing hormone in rat primary cortical neurons against chemical ischemia involves opioid receptor activation. (edu.in)
- A1 adenosine receptor activation reduces hypersensitivity in animal models of chronic pain, but intrathecal adenosine does not produce analgesia to acute noxious stimuli. (asahq.org)
- We have used convergent modeling, mutagenesis and structure activity approaches to gather information about the three-dimensional structure of the receptors and its relationship to binding and activation functions. (nih.gov)
- Another potential method of using the protective effects of AR activation has been achieved through receptor engineering. (nih.gov)
- The cardioprotective effects of activation of the A 2A adenosine receptor (A 2A AR) on ischemia/reperfusion injury in the heart remain controversial. (opencardiovascularmedicinejournal.com)
- Activation of adenosine receptors has been shown to reduce myocardial infarct size in experimental models. (opencardiovascularmedicinejournal.com)
- [4] Activation of A 1 receptors depresses heart by negative inotropic, chronotropic, and dromotropic effects. (ijp-online.com)
- Activation of A 2 receptors cause a reduction in mean arterial pressure by causing a relaxation in vascular smooth muscle cells. (ijp-online.com)
Putative1
- In addition, we have introduced the approach of neoceptors, also intended for eventual use in gene therapy, in which the putative agonist binding site is redesigned to accept only agonist molecules altered in a complementary fashion. (nih.gov)
Potent2
- The agonists, which incorporate the commercially available fluorophore BODIPY [630/650], retain potent and efficacious agonist activity, as demonstrated by their ability to inhibit cAMP accumulation in chinese hamster ovary cells expressing the human adenosine A 1 -receptor. (nottingham.edu.cn)
- Substances developed as potent and selective agents acting through adenosine and P2 receptors have proven useful as pharmacological probes and have potential for treating diseases of the central nervous system, immune system, and cardiovascular system. (nih.gov)
Glutamate3
- Glutamate release evoked by the TRPV-1 receptor agonist, capsaicin, was measured. (asahq.org)
- Capsaicin-evoked glutamate release was inhibited by adenosine or R-PIA (R-N6-(2- phenylisopropyl)-adenosine) in a concentration-dependent manner, with a threshold of 10 nm in both normal and nerve-ligated synaptosomes. (asahq.org)
- 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)
519.625.725.200.100.1001
- AN - traumatic kidney injury: index KIDNEY/ inj HN - 2011 MH - Adenosine A1 Receptor Agonists UI - D058907 MN - D27.505.519.625.725.200.100.100 MN - D27.505.696.577.725.200.100.100 MS - Compounds that bind to and stimulate ADENOSINE A1 RECEPTORS. (nih.gov)
P2Y62
Hyperalgesia1
- 17. Adenosine A1 receptor agonists reduce hyperalgesia after spinal cord injury in rats. (nih.gov)
Antinociception1
- ADENOSINE and synthetic adenosine receptor agonists produce antinociception in a broad range of pain models in animals, including hypersensitivity from nerve injury and inflammation. (asahq.org)
Reperfusion injury1
- Objectives: Adenosine and adenosine A1 receptor agonists exert protective effects against reperfusion injury in different tissues by mediating preconditioning. (beun.edu.tr)
NECA1
- Yöntemler: Denekler herbiri rastgele sekiz hayvan içeren dört gruba ayrıldı: sham kontrol, iskemi-reperfüzyon kontrol, 5'-N-etilkarboksiamidoadenozin (NECA) (non-selektif A1 /A2 agonisti, 0.1 mg/kg, i.v.) tedavili iskemi-reperfüzyon ve teofilin (non-selektif A1 /A2 antagonisti, 20 mg/kg, i.v.) tedavili iskemi-reperfüzyon. (beun.edu.tr)
Adenylyl cyclase1
- D1 receptors stimulate adenylyl cyclase, triggering the production of second messenger, 3',5'-cyclic adenosine monophosphate (cAMP) that regulates protein kinase A (PKA) activity, whereas the D2 receptors have the opposite effect. (brainmatrix.com)
Ischemia1
- We investigated whether ATL 313, a new selective A 2A AR agonist, could reduce myocardial infarct size in a rat ischemia/reperfusion model. (opencardiovascularmedicinejournal.com)
Apoptosis1
- The pharmacological probes designed in our section have been used to demonstrate the connection between purine receptors and apoptosis (programmed cell death). (nih.gov)
Partial1
- This problem might be circumvented by using low-efficacy agonists (partial agonists). (tno.nl)
Modulates2
Rats1
- Autoradiography with [11C]MPDX ex vivo demonstrated decreased A1 receptor binding in the superior colliculus of rats deprived of retino-collicular fibers by contralateral eye enucleation. (nih.gov)
Nucleoside1
- Nucleoside docking to a homology model based on recently reported agonist-bound AR structures characterized the interaction of cycloalkylrelated constituents with a small hydrophobic subpocket in the A1AR. (nih.gov)
Myocardial1
- Myocardial infarction, A 2A adenosine receptor, ATL 313. (opencardiovascularmedicinejournal.com)
Compounds1
- Compounds that bind to and stimulate ADENOSINE A1 RECEPTORS . (nih.gov)
Concentrations2
- Adenosine concentrations, mean arterial pressure (MAP), heart rate (HR), QRS duration and QT interval were evaluated. (ijp-online.com)
- In the second protocol, citalopram infusion did not cause a significant change in plasma adenosine concentrations, but a significant increase observed in EHNA/NBTI groups. (ijp-online.com)
Peripheral1
- This effect is unaltered after peripheral nerve injury and thereby is unlikely to account for the enhanced analgesic efficacy of intrathecal adenosine in this setting. (asahq.org)
Extracellular3
- 2)Structure of the atrial natriuretic peptide receptor extracellular domain in the unbound and hormone-bound states by single-particle electron microscopy. (edu.in)
- My current focus is on receptors for purines, encompassing both adenosine receptors and P2 receptors, which are activated by ATP, UTP and other extracellular nucleotides. (nih.gov)
- Recently, the involvement of extracellular loops of GPCRs have been implicated in the receptor binding of small molecules. (nih.gov)
Binds3
- When an agonist binds to ADORA1, Go protein is activated which, in turn, triggers a cellular response mediated by cAMP. (innoprot.com)
- When an agonist binds to [Arg8]‐AVP, the Gs protein is activated which, in turn, triggers a cellular response mediated by cAMP via adenylate cyclase stimulation. (innoprot.com)
- The function and signaling of dopamine depends on the effect exerted by the type of receptor it binds. (brainmatrix.com)
Caused by a decrease1
- 1997)J Mol Cell Cardiol 29:593-602] and that this decline may be caused by a decrease in coupling between adenosine A1 receptors (AdoA1R) and guanine nucleotide-binding proteins [Cai et al. (aspetjournals.org)
Regulates1
- however, mechanisms by which adenosine regulates activity of RTN chemoreceptors is not known. (eneuro.org)
Vitro1
- PMID- 214392 TI - Regulation of lipogenesis by adenosine 3', 5'-cyclic monophosphate in chicken liver in vitro. (nih.gov)
A1AR2
Radioligand1
- Gabapentin is structurally related to the neurotransmitter GABA (gamma-aminobutyric acid) but it does not modify GABA A or GABA B radioligand binding, it is not converted metabolically into GABA or a GABA agonist, and it is not an inhibitor of GABA uptake or degradation. (nih.gov)
Adenosina1
- Compuestos que se unen a los RECEPTORES DE ADENOSINA A1, estimulándolos. (bvsalud.org)
IC501
- Adenosine agonists inhibited 1 nM [3H]CGS 15943 binding with the following order of activity N6-cyclopentyladenosine (IC50 = 15 nM) greater than 2-chloroadenosine greater than (R)-N6-phenylisopropyladenosine greater than 5'-N6-ethylcarboxamidoadenosine greater than (S)N6-phenylisopropyladenosine greater than CGS 21680 greater than CV 1808 (IC50 greater than 10,000 nM). (aspetjournals.org)
Mediates1
- 1)Type I Gonadotropin-Releasing Hormone Receptor (GnRH-R) Mediates the Antiproliferative Effects of GnRH-II on Prostate Cancer Cells. (edu.in)
Pharmacologically1
- Therefore, we pharmacologically preconditioned male and female hearts with the adenosine A1 receptor agonist N6-cyclohexyl adenosine (CHA). (nih.gov)
Neurons1
- Whole-cell voltage-clamp from chemosensitive RTN neurons shows that exposure to adenosine activated an inward rectifying K + conductance, and at the network level, adenosine preferentially decreased frequency of EPSCs but not IPSCs. (eneuro.org)
Pharmacology1
- [5] Alternative splicing generates two isoforms of the D2 receptor, D2-short (D2s) and D2-long (D2 L ), respectively, and confers different properties that influence its signaling and pharmacology. (brainmatrix.com)
Accumulation1
- The objective of the present study was to investigate whether reduction of central acetylcholine (ACh) accumulation by adenosine receptor agonists could serve as a generic treatment against organophosphate (OP) poisoning. (tno.nl)
NMDA1
- 8)Vasoactive intestinal peptide acts via multiple signal pathways to regulate hippocampal NMDA receptors and synaptic transmission. (edu.in)
Molecular4
- In further FCS studies, both A3 AR and A3 AR R108A underwent similar agonist-induced increases in receptor density and molecular brightness which were accompanied by a decrease in membrane diffusion after agonist treatment. (bvsalud.org)
- 11)Molecular evolution of multiple forms of kisspeptins and GPR54 receptors in vertebrates. (edu.in)
- We are interested in correlating structure of receptors and small molecular drugs with pharmacological properties. (nih.gov)
- The intracellular cAPM-PKA signaling cascades engenders all sorts of modifications of targets that include ion channels, receptors, and carries further to the molecular level. (brainmatrix.com)
Mechanisms1
- 13)Androgen-induced human breast cancer cell proliferation is mediated by discrete mechanisms in estrogen receptor-alpha-positive and -negative breast cancer cells. (edu.in)
Modulation1
- 19)Hippocampal dynorphin immunoreactivity increases in response to gonadal steroids and is positioned for direct modulation by ovarian steroid receptors. (edu.in)
Dopamine2
- Dopamine signals are essentially mediated by five receptors D1-D5, that are encoded by DRD1-DRD5 genes in humans. (brainmatrix.com)
- The dopamine receptor regulation of cAMP impacts PKA and the downstream phosphorylation states of its many substrates. (brainmatrix.com)
Mutant3
- Here, we have compared the membrane organization and downstream signaling of a mutant (R108A, R3.50A) of the adenosine A3 receptor (A3 AR) to that of the wild-type receptor. (bvsalud.org)
- Using bimolecular fluorescence complementation, experiments showed that the R108A mutant retained the ability to recruit ß-arrestin and these receptor/arrestin complexes displayed similar membrane diffusion and organization to that observed with wild-type receptors. (bvsalud.org)
- Constitutively active mutant A3 adenosine receptors, in principle, could be delivered by tissue-targeted vectors for gene therapy. (nih.gov)
Regulation2
Inhibitor1
- inhibitor of facilitated adenosine transport). (ijp-online.com)
Cerebral1
- The application of adenosine A1 receptor agonists in regard to cerebral disorders is hampered by serious cardiovascular side effects. (tno.nl)