Disease relevance of LOC606743

• Pertussis toxin pretreatment and/or the selective A1-adenosine receptor antagonists 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) and (+/-)N6-endonorbornan-2-yl-9-methyladenine (N-0861) were used to prevent activation of A1-adenosine receptors in these cells [1].
• CONCLUSIONS: (1) Endogenous adenosine released during acute global hypoxia causes AV nodal conduction block observed under these conditions in the guinea pig heart in vivo; and (2) this action of adenosine in the AV node is mediated by an A1 adenosine receptor and a pertussis toxin sensitive G protein [2].
• CONCLUSIONS: An A1 adenosine receptor agonist exerts a marked protection against ischaemia induced ventricular arrhythmias and fibrillation in pigs [3].
• In anesthetized rats, N-0840 selectively antagonized A1 adenosine receptor-mediated bradycardia, but generally failed to affect A2 adenosine receptor-mediated vasodilation in the in situ perfused hindquarters (A2/A1 selectivity: > or = 33-fold) [4].
• Effect of A1 adenosine receptor agonist upon cochlear dysfunction induced by transient ischemia [5].

High impact information on LOC606743

• The AV nodal effects of draflazine, ITU, EHNA, and PD81,723 were reversed by the A1 adenosine receptor antagonist 8-cyclopentyltheophylline and adenosine deaminase, implicating endogenous adenosine acting at the A1 adenosine receptor [6].
• CPT reversed the negative dromotropic effect of adenosine on AV nodal conduction and the antiadrenergic effect of N6-cyclopentyladenosine (CPA) mediated by A1-adenosine receptor but not the adenosine-induced decrease in systemic blood pressure caused by the vasodilatory action of the nucleoside mediated by A2-adenosine receptor [7].
• In rat cerebral cortical membranes, [3H]XAC exhibits saturable, specific binding with a Kd of 1.23 nM and a Bmax of 580 fmol/mg of protein at 37 degrees C. N6-(R-Phenylisopropyl)adenosine is a more potent inhibitor of [3H]XAC binding than is 5'-N-ethylcarboxamidoadenosine, indicating that binding is to an A1-adenosine receptor [8].
• Binding of A1 adenosine receptor ligand [3H]8-cyclopentyl-1,3-dipropylxanthine in coronary smooth muscle [9].
• A1-adenosine receptor-mediated inhibition of isoproterenol-stimulated protein phosphorylation in ventricular myocytes. Evidence against a cAMP-dependent effect [10].

Chemical compound and disease context of LOC606743

• It is concluded that the adenosine receptor in guinea pig atrial myocytes, which is known to be linked to K+ channels, is also coupled to adenylate cyclase via a pertussis toxin-sensitive guanine nucleotide-binding protein and shows the characteristics of the A1-adenosine receptor subtype [11].
• The present study was undertaken to determine whether 2-chloro-N6-cyclopentyladenosine (CCPA), a highly selective A1 adenosine receptor agonist, attenuated cochlear dysfunction induced by transient ischemia or not [5].

Biological context of LOC606743

• Role of histidine residues in agonist and antagonist binding sites of A1 adenosine receptor [12].
• CONCLUSIONS: In man, theophylline completely antagonizes the A1-adenosine receptor-mediated prolongation of the A-H interval, but has minimal effect on the A2-receptor-mediated coronary vasodilation, particularly when adenosine concentrations exceed 1.0 microM [13].
• Endogenous adenosine, A1 adenosine receptor, and pertussis toxin sensitive guanine nucleotide binding protein mediate hypoxia induced AV nodal conduction block in guinea pig heart in vivo [2].
• Selective potentiation by an A1 adenosine receptor enhancer of the negative dromotropic action of adenosine in the guinea pig heart [14].
• Three full-length cDNA clones encoding the guinea pig A1 adenosine receptor have been isolated by polymerase chain reaction (PCR) and low-stringency hybridization screening of a guinea pig brain cDNA library [15].

Anatomical context of LOC606743

• FSCPX did not affect the potency of 5'-guanylylimidodiphosphate to inhibit the binding of [3H]CCPA, an A1-adenosine receptor agonist, to brain membranes [16].
• Novel mitogenic effect of adenosine on coronary artery smooth muscle cells: role for the A1 adenosine receptor [17].
• We conclude that adenosine acts as a novel mitogen in porcine CASMC that express the A1 adenosine receptor, possibly contributing to the development of coronary artery disease [17].
• The A1 adenosine receptor radioligand [125I]aminobenzyladenosine bound to a single affinity class of receptors in heart cell membranes from control animals with Bmax and KD of 18.3 +/- 1.0 fmol/mg protein and 3.7 +/- 0.6 nM, respectively (n = 8) [18].
• The distribution of high- and low-affinity species of the A1 adenosine receptor was different in heavy, medium, and light myelin [19].

Associations of LOC606743 with chemical compounds

• The selective A1-adenosine receptor antagonist N-0861 (9-methyladenine derivative) antagonized the effects of adenosine on afterdepolarizations, ITi, and TA [20].
• The A1-adenosine receptor-selective antagonist 8-cyclopentyl-1,3-dipropylxanthine antagonized the effect of 2-chloro-N6-cyclopentyladenosine concentration-dependently, with a KB value of 9.6 nM [11].
• Pretreatment of DDT cells with p-DITC-ADAC (1 microM), followed by washing, reduced [3H]CPX binding to the A1-AdoR by 44% without altering the Kd value for the radioligand to the remaining receptors [21].
• The effects of adenosine on twitch shortenings and aftercontractions were mimicked by the A1-adenosine receptor agonist CPA (N6-cyclopentyladenosine) and by ryanodine [22].
• In vitro and in vivo pharmacological characterization of N6-cyclopentyl-9-methyladenine (N-0840): a selective, orally active A1 adenosine receptor antagonist [4].

Regulatory relationships of LOC606743

• We conclude that phospholamban phosphorylation was inhibited by A1-adenosine receptor activation and that these effects on phospholamban phosphorylation cannot be explained by a reduction in cAMP levels [10].
• The mechanism(s) by which A1 adenosine receptor upregulates PKC (isoforms) are not yet clearly understood [23].

Analytical, diagnostic and therapeutic context of LOC606743

• Evaluation of radioiodinated 8-Cyclopentyl-3-[(E)-3-iodoprop-2-en-1-yl]-1-propylxanthine ([*I]CPIPX) as a new potential A1 adenosine receptor antagonist for SPECT [24].

References