Adrenergic-cholinergic interactions in left atria. II. Comparison of the antagonism of inotropic responses to alpha- and beta-adrenoceptor stimulation and BAY K 8644 by carbachol, D-600, and nifedipine.
The muscarinic agonist carbachol has previously been shown to reverse positive inotropic responses of rabbit left atrial strips to equiactive doses of the beta-adrenoceptor agonist isoproterenol and to the alpha-adrenoceptor agonist phenylephrine. Responses to phenylephrine were measured in the presence of the beta-blocker timolol. However, carbachol was not able to reverse the increase in tension produced by elevating the extracellular Ca2+ concentration. To gain more information about the nature of the functional interaction of carbachol with alpha- and beta-receptor stimulants in left atria, the interaction of carbachol with these agonists, as well as with elevated Ca2+ and the Ca2+ activator compound BAY K 8644, was compared with that of the Ca2+ antagonists D-600 and nifedipine. The results demonstrate that the Ca2+ antagonists exhibit a selectivity similar to that of carbachol, in that responses to both isoproterenol and phenylephrine plus timolol were blocked by low concentrations of D-600 and nifedipine, which had no effect on positive inotropic responses to elevated Ca2+. Higher concentrations of these antagonists shifted the Ca2+ dose-response curve to the right. In addition, although phenylephrine and BAY K 8644 increased tension to a similar extent, responses to phenylephrine were more sensitive than responses to BAY K 8644 to inhibition by both carbachol and D-600. These similarities between the effects of low concentrations of D-600 and nifedipine and those of carbachol are consistent with the hypothesis that carbachol antagonizes responses to alpha- and beta-receptor stimulation in left atria primarily by blocking increases in Ca2+ influx produced by these agonists.(ABSTRACT TRUNCATED AT 250 WORDS)
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D002122:Calcium Chloride / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology*; D005711:Gallopamil / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D011817:Rabbits
D010656:Phenylephrine; D005711:Gallopamil; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D002217:Carbachol; D009543:Nifedipine; D007545:Isoproterenol; D002122:Calcium Chloride