Further characterization of the receptors involved in the positive inotropic effect of histamine on rabbit papillary muscle.
The effects of histamine on the force of contraction and calcium-dependent action potentials were studied in rabbit ventricular papillary muscles. The positive inotropic effect of histamine seems to be dependent on stimulation of H1 and H2 receptors. The H1 antagonist chlorpheniramine produced a competitive blockade of the positive inotropic effects of histamine. Cimetidine produced a competitive blockade, which was apparent only after blockade of H1 receptors. Histamine increased the maximum upstroke velocity of slow action potentials. This effect can be entirely accounted for by stimulation of H2 receptors. The phosphodiesterase inhibitor 3-isobutyl-methyl-xanthine potentiated the H2 receptor mediated effects of histamine on the force of contraction and slow action potentials. We conclude that rabbit ventricular muscle possesses both H1 and H2 receptors that mediate the positive inotropic effect of histamine. The H2-mediated effect seems to be causally related to an increase in the calcium slow inward current and is probably linked to an enhanced cellular cyclic adenosine monophosphate content. The mechanism of the H1-mediated positive inotropic effect remains unknown.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002744:Chlorpheniramine / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology*; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects* / Q000502:physiology; D011817:Rabbits; D011968:Receptors, Histamine / Q000187:drug effects* / Q000502:physiology; D011969:Receptors, Histamine H1 / Q000187:drug effects / Q000502:physiology; D011970:Receptors, Histamine H2 / Q000187:drug effects / Q000502:physiology
D011968:Receptors, Histamine; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D002744:Chlorpheniramine; D002927:Cimetidine; D006632:Histamine; D015056:1-Methyl-3-isobutylxanthine