THE NEGATIVE CHRONOTROPIC EFFECT OF TYRAMINE ON ISOLATED GUINEA-PIG ATRIA

¹ Department of Pharmacology, The Wm. S. Merrell Company, Division of Richardson-Merrell Inc., Cincinnati, Ohio

The influence of various agents on the negative chronotropic effect of tyramine was studied on atria isolated from guinea pigs pretreated with reserpine (5 mg/kg i.p. 24 hours prior to the experiment). In this atrial preparation, tyramine at concentrations of 10^-4 M or higher produced a negative chronotropic effect. This effect of tyramine was not antagonized by atropine (10^-6 to 10^-5; M), scopolamine (10^-6 to 10^-5 M) or phentolamine (3 x 10^-7 M). However, in the presence of propranolol (10^-7 to 10^-6 M) or physostigmine (10^-7 M), the negative chronotropic effect of tyramine was enhanced. Physostigmine, even in the presence of propranolol, further enhanced the effect of tyramine. The enhancement of the effect of tyramine by physostigmine was blocked by atropine but not by hexamethonium (10^-4 M). Atropine did not block the enhancement of the effect of tyramine by propranolol. The results suggest that the negative chronotropic effect of tyramine is not mediated through alpha or beta adrenergic receptors or muscarinic receptors. Although tyramine appears to be able to release acetyicholine or an acetylcholine-like substance, this activity does not contribute to the observed effect of tyramine except in the presence of physostigmine. Thus, the present results support the view that the negative chronotropic effect of tyramine is due to a direct depressant effect on the atrial pacemaker.