Ransnas_1986_J.Mol.Cell.Cardiol_18_807

Cat myocardium was used to investigate muscarinic receptor function in atria and ventricles. Carbachol and oxotremorine were used to determine agonist binding to the muscarinic receptors. It was found that carbachol was bound with almost the same characteristics in atria (KdH 1 microM; KdL 150 microM) as in ventricles (KdH 3 microM; KdL 150 microM). However, in the presence of guanylylimidodiphosphate Gpp(NH)p a difference was apparent so that the ventricular curve was shifted to a majority of low affinity sites whereas in atria two affinity sites remained even if the guanine nucleotide concentration was increased to 10 mM. Oxotremorine was bound with almost equal affinity in both atria and ventricles. The addition of Gpp(NH)p left all the receptors in the low affinity state irrespective of receptor localisation. The two agonists were also used to determine inhibition of adenylate cyclase activity. It was shown that the magnitude of adenylate cyclase inhibition was more pronounced in ventricles than in atria whether it was induced by oxotremorine or carbachol. When the effects of muscarinic agonists were determined on phosphatidylinositol metabolism it was shown that carbachol mediated a greater effect in atria than in ventricles. Almost no effect was seen with oxotremorine on phosphatidylinositol breakdown. Pirenzipine binding showed the presence of M1 receptors both in atria and ventricles. On the basis of diversity of muscarinic agonists on function and receptor occupancy it is suggested that heterogeneity exists for muscarinic receptors in both atria and ventricles.