Separate receptors mediating the positive inotropic and chronotropic effect of histamine in guinea-pig atria.
The direct positive inotropic effect of histamine was studied on paced left atrial preparation from guinea pigs. Histamine (10(-8) to 10(-4) M) increased the maximum tension developed in left atria incubated at 35degreesC and driven at 2 Hz. The maximum increase in tension was 60% of that observed with norepinephrine. Metiamide (3 X 10(-5) M, a specific H2-receptor antagonist) did not alter the inotropic response of left atria to histamine. However, tripelennamine (a typical H1-receptor antagonist) competitively shifted the histamine inotropic dose--response curve to the right at concentrations from 10(-8) to 10(-7) M. Higher concentrations (3 X 10(-7) and 10(-6) M) caused little further additional shift to the right. The positive chronotropic effect of histamine on spontaneously beating atria was competitively antagonized by metiamide (10(-6) and 3 X 10(-6) M). These results demonstrate that in guinea-pig atria histamine increases myocardial contractility by an interaction with receptors closely related to classical H1-receptors while its chronotropic effect is mediated by interaction with H2-receptors.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D004347:Drug Interactions; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000294:innervation* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects*; D006632:Histamine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008785:Metiamide / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D011968:Receptors, Histamine / Q000187:drug effects*; D012110:Reserpine / Q000494:pharmacology; D013268:Stimulation, Chemical; D014309:Tripelennamine / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D011968:Receptors, Histamine; D014309:Tripelennamine; D008785:Metiamide; D006632:Histamine; D012110:Reserpine