title: Further characterization of the guinea pig left atrial tension response to histamine by use of selective agonists.
abstract: 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.
mesh_terms: 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
chemical_list: 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