Adenosine receptor-mediated coronary artery relaxation and cyclic nucleotide production

Abstract

We investigated the involvement of adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP) in adenosine (ADO) receptor-mediated coronary artery relaxation. Rings from left anterior descending coronary artery, with the endothelium mechanically removed, contracted with prostaglandin F2 alpha and relaxed in a concentration-dependent manner to ADO, 2-chloroadenosine (CAD), l-N6-(2-phenylisopropyl)adenosine (R-PIA), and 5'-(N-ethylcarboxamido)adenosine (NECA). These relaxations were blocked by addition of the ADO receptor antagonist 8-(sulfophenyl)theophylline (8-SPT), indicating ADO receptor involvement. In an endothelium-free membrane preparation, ADO, CAD, and R-PIA all stimulated adenylate cyclase activity in a concentration-dependent manner, and these responses were blocked by 8-SPT. The increase in adenylate cyclase activity produced by ADO, CAD, and R-PIA was completely dependent on the presence of guanosine 5'-triphosphate, suggesting G protein involvement. Surprisingly, NECA and CGS-21680 did not increase adenylate cyclase activity. Unlike atrial natriuretic factor, neither NECA, CAD, R-PIA, nor ADO increased guanylate cyclase activity, suggesting that cGMP is not involved in ADO receptor-mediated relaxation. Data presented in this study support the hypothesis that ADO receptor-mediated coronary artery relaxation may involve cAMP; however, the inability of NECA and CGS-21680 to stimulate adenylate cyclase suggests that the ADO receptor-signaling mechanisms in coronary artery may be more complicated than agonist interaction with a single adenylate cyclase-coupled A2 adenosine receptor.

A2A Adenosine Receptor Deficiency Leads to Impaired Tracheal Relaxation via NADPH Oxidase Pathway in Allergic Mice

“…Thus, the biochemical basis of bronchial hyper-reactivity and bronchoconstriction in asthma remains only partially understood. shown the involvement of A 2A AR in smooth muscle relaxation from different organs via the cAMP-PKA pathway (Cushing et al, 1991;Haynes, 2000;Gopalakrishnan et al, 2002;Radenković et al, 2005), but this is the first study to show its involvement in tracheal smooth muscle relaxation. A 2A WT sensitized and A 2A KO control had decreased cAMP and p-PKA levels, thus suggesting that the deficiency of A 2A AR leads to decreased tracheal relaxation due to altered cAMP-PKA signaling.…”

Adenosine activates ATP-sensitive potassium channels in arterial myocytes via A2 receptors and cAMP-dependent protein kinase.

“…The PKAinhibitor peptide completely blocked adenosine activation of KATP currents in mesenteric artery myocytes (Fig. 5) (1995) ciated with an elevation in intracellular cAMP and activation of PKA (19,22) A number of other endogenous vasodilators, including calcitonin gene-related peptide (39), vasoactive intestinal peptide (40), prostaglandins (9,41), and 031-adrenoceptor agonists (42,43), have been shown to act in part through a GLIBsensitive mechanism. These smooth muscle relaxants are also known to stimulate adenylyl cyclase and elevate intracellular cAMP (44)(45)(46).…”

Identification of A2a Adenosine Receptor Domains Involved in Selective Coupling to GS

“…The A 2a AR and A 2b AR are coupled to G s activation with the resulting stimulation of adenylyl cyclase, increase in cellular cAMP levels and protein kinase A activation (2). Activation of the A 2a AR-G s signal transduction pathway appears to be involved in adenosine-induced vasodilation (12,13), inhibition of platelet aggregation (14), and modulation of neutrophil function (15,16) although the complete signal transduction pathways have yet to be delineated.…”