A Question of the Specificity of Rabbit Atrial Chronotropic Histamine Receptors and Agents Which Affect Their Activity

The histamine chronotropic response of rabbit atria appears to be controlled by both H1 and H2 receptors and can be blocked in part by either metiamide (an H2 antagonist) or diphenhydramine (an H1 antagonist), while both 2- and 4-methylhistamine (H1 and H2 agonists, respectively) stimulated the chronotropic response. At low agonist concentrations, the simultaneous presence of both H1 and H2 blockers results in considerably less inhibition than could be expected from calculations of individual inhibition data, suggesting that some sites behave as if they have both H1 and H2 properties. Additional compounds were tested for specific action on H1 and H2 receptors: 2-(2-pyridyl) ethylamine, reported to be an H1 agonist, appears to stimulate rabbit atria by releasing norepinephrine and guinea pig atria by releasing both norepinephrine and histamine; while dimaprit, reported to be an H2 agonist, may stimulate histamine receptors directly but has a nonspecific depressant action on rabbit atria which interferes with its use as an agonist in this species.