THE EFFECT OF DRUGS ON UPTAKE AND RELEASE OF CATECHOLAMINES IN THE ISOLATED LEFT ATRIUM OF THE GUINEA PIG

¹ Department of Pharmacology, State University of New York, Downstate Medical Center, Brooklyn, New York

Study of the distribution of endogenous norepinephrine (NE) in various parts of the guinea pig heart indicates that the right atrium contains more NE than the left atrium; the ventricles contain the least amount of NE. Reserpine and tyramine reduced the endogenous NE content of the electrically-driven, isolated, bisected left atrium of the guinea pig, while bretylium, cocaine and suprathreshold voltage stimulation did not affect NE levels. No correlation was observed between NE depletion and degree of inotropism which these agents produce in the normal atrium. NE uptake was proportional to the concentration of NE in the bathing medium and was greater at 37°C than at room temperature. Atria incubated with epinephrine (E) showed elevated E levels and decreased NE levels. Uptake of NE was blocked by cocaine, bretylium, SY28 and phenoxybenzamine. No detectable NE uptake was observed in atria obtained from guinea pigs pretreated with reserpine. Study of the subcellular distribution of catecholamines in whole guinea pig heart indicated that endogenous NE is restricted to the crude, microsomal and supernatant fractions. Atria show a similar distribution. Atria incubated with NE or E showed increases in catecholamine content of all fractions, which were greater in the supernatant than in the microsomal fraction.