Characterization of the adenosine receptor in porcine coronary arteries

Abstract

1 Relaxant responses of ring preparations from porcine ventricular coronary arteries to adenosine and various stable adenosine analogues were investigated in vitro. 2 The adenosine analogues did not produce contraction but elicited almost complete relaxation of coronary arteries preconstricted with 3 pJm prostaglandin F2 (PGF2z), even after removal of the endothelium.3 The order of potency, was 5'-N-ethylcarboxamide-adenosine (NECA) > 242-phenylethylamino)5'-adenosine (CPA) > adenosine > ATP = ADP which suggested the presence of adenosine A2-receptor subtypes. 4 There was an excellent correlation between the calculated pD2 values on coronary arteries and the pKD values at adenosine A2 binding sites, whereas no correlation was obtained when the pD2 values were compared to the pKD values at adenosine Al-binding sites on membranes from porcine striata.5 The relaxant effects of adenosine and its analogues were competitively antagonized by 8-(p-sulphophenyl)-theophylline (8-SPT), producing pA2 values similar to the respective pKD value of the antagonist at adenosine A2 binding sites. 6 It is suggested that the porcine coronary artery possesses adenosine A2 receptors which seem to be similar to the adenosine A2 binding site in pig striatum, whereas no evidence was obtained for the presence of adenosine A1 receptors.

Cardiac purinergic signalling in health and disease

“…This study also showed that contractile responses of human coronary arteries to α,β-meATP and the stable pyrimidine analogue, uridine 5′-O-3-thiotriphosphate, were consistent with activation of P2X1R and P2Y2R, respectively. UTPevoked contractions of porcine coronary artery smooth muscle cells also appear to be mediated predominantly by P2Y2R [422][423][424][425][426]. The adenosine may be released directly from cardiomyocytes and endothelial cells after intra-and extracellular breakdown of ATP, respectively [427].…”

Role of A2A‐adenosine receptor activation for ATP‐mediated coronary vasodilation in guinea‐pig isolated heart

“…1991;Fleetwood & Gordon, 1987;Gordon, 1986;Hopwood & Burnstock, 1987;Matsumoto et al, 1997;Olsson & Pearson, 1990;Simonsen et al, 1997;Vials & Burnstock, 1994;Godecke et al, 1996). However, antagonism of ATP-induced coronary vasodilation by AdoR antagonists implicates activation of A 2A -AdoRs in the action of ATP (White & Angus, 1987;Bunger et al, 1975;King et al, 1990;Kroll & Schrader, 1993). Until now the lack of selective and potent antagonists for either P 2Y or A 2A -adenosine receptors has been an obstacle to the identi®cation of the type receptor(s) that mediate ATP-induced coronary vasodilation.…”

Purinergic Signaling and Blood Vessels in Health and Disease

“…It can arise directly from cardiomyocytes after intracellular breakdown of ATP and after extracellular breakdown of ATP released from endothelial cells (Pekka Raatikainen et al, 1991). It was suggested that the vasodilator actions of adenosine were mediated by A 2 receptors (Leung et al, 1985;Daly et al, 1986;Odawara et al, 1986;see Mustafa et al, 2009), probably located on endothelial cells (Kroll et al, 1987;Des Rosiers and Nees, 1987;Ramagopal et al, 1988a;Balcells et al, 1992;King et al, 1990), perhaps together with another P1 receptor subtype . Methylxanthines antagonized A 2 receptor-mediated coronary vasodilation (Ramagopal Purinergic Signaling and Blood Vessels et al, 1988b).…”