• The adenosine receptors (or P1 receptors) are a class of purinergic G protein-coupled receptors with adenosine as the endogenous ligand. (wikipedia.org)
  • The complex pharmacology of G-protein-coupled receptors (GPCRs) is defined by their multi-state conformational dynamics. (nature.com)
  • Newer adenosine receptor agonists and antagonists are much more potent and subtype-selective, and have allowed extensive research into the effects of blocking or stimulating the individual adenosine receptor subtypes, which is now resulting in a new generation of more selective drugs with many potential medical uses. (wikipedia.org)
  • Specific A1 antagonists include 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX), and Cyclopentyltheophylline (CPT) or 8-cyclopentyl-1,3-dipropylxanthine (CPX), while specific agonists include 2-chloro-N(6)-cyclopentyladenosine (CCPA). (wikipedia.org)
  • Second, different agonists vary in efficacy and can stimulate receptor activity to a different extent 5 . (nature.com)
  • The regional hemodynamic effects of adenosine A2A and A2B selective agonists were investigated in conscious rats. (bvsalud.org)
  • These results suggest that the development of A2B receptor agonists to induce vasodilatation in the kidney may provide a good therapeutic approach for the treatment of acute kidney injury. (bvsalud.org)
  • Most older compounds acting on adenosine receptors are nonselective, with the endogenous agonist adenosine being used in hospitals as treatment for severe tachycardia (rapid heart beat), and acting directly to slow the heart through action on all four adenosine receptors in heart tissue, as well as producing a sedative effect through action on A1 and A2A receptors in the brain. (wikipedia.org)
  • Adenosine receptors are closely associated with dopamine receptors and form heteromer s with them. (adxs.org)
  • At the same time, adenosine modulates striatal DA release by stimulating glutamate release at adenosine receptors in the striatum , which increases dopamine levels. (adxs.org)
  • These two receptors also have important roles in the brain, regulating the release of other neurotransmitters such as dopamine and glutamate, while the A2B and A3 receptors are located mainly peripherally and are involved in processes such as inflammation and immune responses. (wikipedia.org)
  • The A1, together with A2A receptors of endogenous adenosine play a role in regulating myocardial oxygen consumption and coronary blood flow. (wikipedia.org)
  • GPCRs recognize a large variety of endogenous extracellular signaling molecules transmitting their corresponding signals inside the cell, and this process can be modulated by synthetic ligands or drug molecules. (nature.com)
  • Some of these compounds are still derived from adenosine or from the xanthine family, but researchers in this area have also discovered many selective adenosine receptor ligands that are entirely structurally distinct, giving a wide range of possible directions for future research. (wikipedia.org)
  • Pharmacological studies have shown that KW-6356 is a potent and selective ligand for the A2A receptor (the -log of inhibition constant = 9.93 ± 0.01 for human receptor) with a very low dissociation rate from the receptor (the dissociation kinetic rate constant = 0.016 ± 0.006 minute-1 for human receptor). (bvsalud.org)
  • KW-6356 is a novel adenosine A2A (A2A) receptor antagonist/inverse agonist, and its efficacy as monotherapy in Parkinson's disease (PD) patients has been reported. (bvsalud.org)
  • In this study, we investigated the in vitro pharmacological profile of KW-6356 as an A2A receptor antagonist/inverse agonist and the mode of antagonism and compared them with istradefylline. (bvsalud.org)
  • Crystallography of KW-6356- and istradefylline-bound A2A receptor have indicated that interactions with His2506.52 and Trp2466.48 are essential for the inverse agonism, whereas the interactions at both deep inside the orthosteric pocket and the pocket lid stabilizing the extracellular loop conformation may contribute to the insurmountable antagonism of KW-6356. (bvsalud.org)
  • SIGNIFICANCE STATEMENT: KW-6356 is a potent and selective adenosine A2A receptor antagonist/inverse agonist and exhibits insurmountable antagonism, whereas istradefylline, a first-generation adenosine A2A receptor antagonist, exhibits surmountable antagonism. (bvsalud.org)
  • Xanthine derivatives such as caffeine and theophylline act as non-selective antagonists at A1 and A2A receptors in both heart and brain and so have the opposite effect to adenosine, producing a stimulant effect and rapid heart rate. (wikipedia.org)
  • The A2A -selective agonist CGS 21680 produced a striking increase in heart rate (HR) and hindquarters vascular conductance (VC) that was accompanied by a significant decrease in mean arterial pressure (MAP) in conscious rats. (bvsalud.org)
  • Taken together, these data indicate that A2A and A2B receptors are regionally selective in their regulation of vascular tone. (bvsalud.org)
  • One cryoEM and over 50 high-resolution X-ray crystallographic structures are available for antagonist- or agonist-bound A 2A AR and for its ternary complex with an agonist and an engineered G protein, making this receptor an excellent model system for investigating GPCR structural dynamics. (nature.com)
  • In addition, we determined cocrystal structures of A2A receptor in complex with KW-6356 and istradefylline to explore the structural basis of the antagonistic properties of KW-6356. (bvsalud.org)
  • Structural studies of adenosine A2A receptor in complex with KW-6356 and istradefylline explain the characteristic differences in the pharmacological properties of KW-6356 and istradefylline. (bvsalud.org)
  • Therefore, smFRET has been limited to studies of inter-receptor interactions in cellular membranes and receptors in detergent environments. (nature.com)
  • Here, the aldehyde form (retinal) is bound to the protein rhodopsin in the membranes of rod and cone cells. (pressbooks.pub)
  • Although the effects of caffeine excess have been widely studied, little information is available on potential interactions between the other active ingredients of energy drinks and caffeine. (researchgate.net)
  • One of the active ingredients often mentioned as a candidate for interactions with caffeine is the beta-amino acid, taurine. (researchgate.net)
  • However, based on this review regarding possible interactions between caffeine and taurine, we conclude that taurine should neutralize several untoward effects of caffeine excess. (researchgate.net)
  • At the cardiovascular level, they concluded that 'if there are any interactions between caffeine and taurine, taurine might reduce the cardiovascular effects of caffeine. (researchgate.net)
  • Although these interactions remain to be further examined in humans, the physiological functions of taurine appear to be inconsistent with the adverse cardiovascular symptoms associated with excessive consumption of caffeine-taurine containing beverages. (researchgate.net)
  • For instance, both A1 receptors and A2A play roles in the heart, regulating myocardial oxygen consumption and coronary blood flow, while the A2A receptor also has broader anti-inflammatory effects throughout the body. (wikipedia.org)
  • 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)
  • Among other things, adenosine is used for autoregulation in the event of an imminent lack of energy in the cell (e.g. when the cell's performance is overloaded or when there is a lack of oxygen): If the ATP content in a cell drops, more adenosine is produced as a hydrolysis product. (adxs.org)
  • Isolated, perfused hearts from rats that were fed the ketone diet had greater free energy available from ATP hydrolysis during increased work than did hearts from rats on the other diets as shown by using [ 31 P]-NMR spectroscopy. (epiphanyasd.com)
  • 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)
  • Calcitriol inside of cells acts by binding a vitamin D receptor (VDR), which results in most of the vitamin's physiological effects. (pressbooks.pub)
  • Through this mechanism, the increased level of adenosine after sleep deprivation could affect the light sensitivity of the circadian clock. (adxs.org)
  • His seminal contributions, documented in more than 490 publications and 27 book chapters, encompass key developments such as mechanism-based PK-PD models, which incorporate biologically realistic considerations such as understanding of target site distribution and receptor theory. (eacpt.org)
  • This effect on the A1 receptor also explains why there is a brief moment of cardiac standstill when adenosine is administered as a rapid IV push during cardiac resuscitation. (wikipedia.org)
  • This receptor has an inhibitory function on most of the tissues in which it is expressed. (wikipedia.org)
  • Most tissues respond to VDR bound to calcitriol and the result is moderation of calcium and phosphate levels in cells. (pressbooks.pub)
  • Therefore, purpose of this study was to assess acute electrophysiologic effects of caffeine and taurine, two of the main ingredients of energy drinks, in an experimental whole-heart model. (researchgate.net)
  • Part of this adenosine is discharged from the cell and binds to adenosine receptors of neighboring cells, which is supposed to compensate for the disturbed balance between energy consumption and energy supply. (adxs.org)
  • It acts in differentiation of stem cells through a specific cellular retinoic acid receptor. (pressbooks.pub)
  • 0.05) increased lipid peroxidation and alterations in antioxidant defence systems occasioned by drop in catalase and superoxide dismutase enzymes (serum, liver, heart, brain and kidneys) of the rats. (springeropen.com)
  • Istradefylline is a first-generation A2A receptor antagonist approved for use as adjunct treatment to levodopa/decarboxylase inhibitor in adult PD patients experiencing "OFF" episodes. (bvsalud.org)
  • Eight monophasic action potentials and ECG recordings showed a significant abbreviation of action potential duration (APD90 ), QT interval and effective refractory periods (ERP) after caffeine treatment. (researchgate.net)
  • Here, we performed smFRET experiments on functionally active human A 2A adenosine receptor (A 2A AR) molecules embedded in freely diffusing lipid nanodiscs to study their intramolecular conformational dynamics. (nature.com)
  • Adenosine is found in almost all body cells. (adxs.org)
  • The adenosine A1 receptor has been found to be ubiquitous throughout the entire body. (wikipedia.org)
  • Adenosine receptors play a key role in the homeostasis of bone. (wikipedia.org)
  • Studies have found that blockade of the A1 Receptor suppresses the osteoclast function, leading to increased bone density. (wikipedia.org)
  • Methods and results: 25 rabbit hearts were excised, retrogradely perfused and assigned to two groups. (researchgate.net)
  • Presynaptically, it reduces synaptic vesicle release while post synaptically it has been found to stabilize the magnesium on the NMDA receptor. (wikipedia.org)
  • 2 ms) exchange between the active-like and inactive-like conformations in both apo and antagonist-bound A 2A AR, explaining the receptor's constitutive activity. (nature.com)
  • NanoBRET ligand binding studies were used to confirm receptor selectivity. (bvsalud.org)