A positive inotropic response of guinea pig isolated atria to histamine not mediated via H1 or H2 receptors

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Abstract
The positive chronotropic responses of guinea pig isolated right atria to histamine were antagonized by metiamide (pA2 [effective concentration of agonist to antagonist], 5.95), confirming their H2 receptor classification. The positive inotropic responses of paced left atria were antagonized to some extent by mepyramine to give a pA2 value of 7.87, indicating the involvement of H1 receptors. A limit to the shift of cumulative dose-response curves for the inotropic response suggested an H1 receptor resistant component. The inotropic response to sequentially administered histamine was biphasic. On lowering the temperature to 25.degree. C, the 2 components became more demarcated and separated by a negative phase. Only the primary positive component and the negative component were antagonized by mepyramine. At 38.degree. C, the response was similarly converted to a monophasic one. The residual responses were resistant to metiamide and propranolol antagonism and therefore not mediated via H1, H2 or .beta.-adrenergic receptors.