Cardiac adenosine receptors are coupled to adenylate cyclase inhibition. In the guinea pig heart, the relative agonist potencies observed for adenylate cyclase inhibition were R-N6-phenylisopropyladenosine (R-PIA) = N6-cyclohexyladenosine > 5′-N-ethylcarboxamidoadenosine [Formula: see text]S-PIA. In both atrial and ventricular membranes, the antagonists 8-phenyltheophylline (8-PT) and isobutylmethylxanthine (IBMX) also showed similar affinities for atrial and ventricular adenosine receptors. The same pattern of relative agonist potencies was observed in experiments performed at either 25 or 37 °C. However, the maximal inhibition produced by R-PIA in atrial membranes decreased from 30.8 ± 3.2% (n = 7) at 25 °C to 18.8 ± 1.6% (n = 4) at 37 °C. No such difference in maximal inhibition was observed with ventricular membranes at these two temperatures (34.5 ± 1.6%, n = 6 at 25 °C and 35.3 ± 0.9%, n = 11 at37 °C). While there was no change in agonist potencies, the affinities of the antagonists 8-PT and IBMX at cardiac adenosine A1 receptors were affected by temperature. At 25 °C, the pKD values for 8-PT and IBMX in ventricular membranes were 4.65 ± 0.21 (n = 3) and 4.55 ± 0.20 (n = 3), respectively. Their affinities were 7-to 19-fold higher at 37 °C, the pKD values being 5.93 ± 0.12 (n = 7) (p < 0.02) and 5.38 ± 0.18 (n = 3) (p < 0.05), respectively. Over the same temperature range, the affinity of the muscarinic antagonist atropine was increased only by two-fold. These results suggest that (i) atrial and ventricular adenosine receptors are similar, (ii) atrial and ventricular adenylate cyclases are different in terms of temperature effects, and (iii) antagonist affinities at cardiac A1 receptors are critically dependent on temperature.
Functional coupling of SSTR4, a major hippocampal somatostatin receptor, to adenylate cyclase inhibition, arachidonate release and activation of the mitogen-activated protein kinase cascade.
