THE ABILITY OF TYRAMINE TO LIBERATE CATECHOLAMINES IN VIVO

¹ Department of Pharmacology, Harvard Medical School, Boston, Massachusetts

In anesthetized, atropinized dogs, intravenous nicotine produces a marked rise in the catecholamine output from the adrenal gland. Tyramine, in doses which produce a blood pressure response equal to or greater than that caused by nicotine, does not cause the liberation of catecholamines into adrenal venous blood. After adrenalectomy, nicotine administration leads to a rise in arterial plasma catecholamines, predominantly norepinephrine, which is simultaneous with the blood pressure effect. Tyramine only occasionally produces slight elevations in plasma catecholamines in adrenalectomized dogs. In adrenalectomized dogs pretreated with phenoxybenzamine, tyramine administration causes an increase in plasma catecholamine levels more frequently. However, the peak of the catecholamine rise occurs after the time when the maximal blood pressure response would be expected in dogs not pretreated.

Rats given large doses of tyramine have lower levels of heart, spleen and brown fat catecholamines than salinenjected controls. This depletion is maximal in spleen and brown fat after 5 minutes. After 30 minutes, only the heart becomes further depleted.

It is postulated that nicotine liberates catecholamines from nerve terminals, and from chromaffin granules of the adrenal medulla and from those associated with sympathetic nerves. Tyramine depletes a third compartment, in which circulating catecholamines are bound, and which is the site of uptake of exogenous catecholamines. Tyramine does not deplete chromaffin granules directly, although it may do so indirectly, as the granules lose catecholamines at an accelerated rate to replenish other stores.