Ca2+ dependence of positive inotropic responses of guinea pig isolated cardiac preparations to cAMP-generating and cAMP-independent agonists.
The effects of procedures which diminish Ca2+ influx into myocardial cells on responses of isolated cardiac preparations to cAMP-independent histamine H1 receptor stimulation and cAMP-generating beta-receptor stimulation were measured. The histamine response of guinea pig left atria, which appears to be primarily mediated by H1 receptors, was depressed to a greater extent than was the response of this preparation to isoproterenol by decreasing the extracellular Ca2+ concentration, and by the Ca2+ influx blocker D-600. Similarly, while the H1 agonist 2-pyridylethylamine dihydrochloride (PEA) produced increases in tension of a similar magnitude as the partial beta-agonist salbutamol in both left atria and in papillary muscles, responses of both preparations to PEA were depressed to a significantly greater extent by decreasing the extracellular Ca2+ concentration than were responses to salbutamol. Overall, both the basal developed force of papillary muscles and the responses of these preparations to H1 and beta-receptor stimulation appeared to be less depressed by decreasing the extracellular Ca2+ concentration than were those of left atria. These results indicate that responses mediated via cAMP-independent H1 receptors, like those arising from alpha-receptor stimulation, are more sensitive to procedures which diminish Ca2+ influx than are responses arising from stimulation of cAMP-generating beta-receptors. This may reflect differences in the mechanisms by which stimulation of H1, alpha-, and beta-receptors give rise to positive inotropic responses. In addition, left atria may be more dependent than papillary muscles on extracellular Ca2+ for the support of contraction.
D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology*; D000242:Cyclic AMP / Q000502:physiology*; D005260:Female; D005711:Gallopamil / Q000494:pharmacology; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D011968:Receptors, Histamine / Q000187:drug effects; D013268:Stimulation, Chemical
D011725:Pyridines; D011968:Receptors, Histamine; D005711:Gallopamil; D006632:Histamine; C006183:2-(2-aminoethyl)pyridine; D000242:Cyclic AMP; D007545:Isoproterenol; D000420:Albuterol; D002118:Calcium