Further characterization of the guinea pig left atrial tension response to histamine by use of selective agonists.
1. The responses of guinea pig left atrial tension and right atrial rate to histamine receptor agonists and histamine were compared. 2. Single doses of histamine and another non-selective agonist, N,N-dimethylhistamine, produced biophasic inotropic responses, with an initial increase in tension and a secondary sustained tension increase separated by a negative inotropic component. 3. Selective H1-receptor agonists -- 2-methylhistamine, 3-methylhistamine and 2-pyridylethylamine (2-PEA) -- also exhibited biphasic inotropic responses. 2-PEA did so only after blockade with propranolol or in atria from reserpine-pretreated animals, indicating an additional release of endogenous catecholamines which masked the biophasic response. 4. Selective H2-receptor agonists -- 4-methylhistamine and dimaprit -- failed to produce biphasic responses except at high concentrations only in the case of 4-methylhistamine. 5. The biophasic responses were converted to monophasic responses by mepyramine. This was a result of antagonism of the initial positive component and the secondary negative component which were therefore mediated via H1-receptors. The production of a biphasic inotropic response therefore depends upon these two components which were exhibited preferentially by the H1-receptor-selective agonists.
D000818:Animals; D005260:Female; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008761:Methylhistamines / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D011969:Receptors, Histamine H1 / Q000187:drug effects; D011970:Receptors, Histamine H2 / Q000187:drug effects
D008761:Methylhistamines; D011725:Pyridines; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; C025566:4-methylhistamine; D006632:Histamine; C006183:2-(2-aminoethyl)pyridine; C026259:2-methylhistamine; D011738:Pyrilamine