RT Journal Article SR Electronic T1 RESERPINE-INDUCED DEPLETION OF THE NOREPINEPHRINE STORES: IS IT A RELIABLE CRITERION FOR THE CLASSIFICATION OF THE MECHANISM OF ACTION OF SYMPATHOMIMETIC AMINES? JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 640 OP 653 VO 188 IS 3 A1 M. A. Luchelli-Fortis A1 S. Z. Langer YR 1974 UL http://jpet.aspetjournals.org/content/188/3/640.abstract AB Phenylephrine increases the outflow of 3H-norepinephrine from isolated guinea-pig atria and from the isolated cat nictitating membrane. This releasing effect was observed with 3 x 10-5 M, a concentration which corresponds to the range in which phenylephrine elicits its pharmacological effects. In both tissues approximately 75% of 3H-norepinephrine released by phenylephrine was collected as 3H-metabolites. The main metabolic pathway for the 3H-norepinephrine released was through the 3H-deaminated glycol (3,4-dihydroxyphenylglycol). Depletion of the norepinephrine stores by pretreatment with reserpine did not modify the dose-response curves to phenylephrine in guinea-pig atria or in the cat nictitating membrane. Yet, inhibition of monoamine oxidase by pretreatment with pargyline in guinea-pig atria induced a nearly 1 log unit shift to the left in the dose-response curve to phenylephrine while it did not affect responses to norepinephrine. Exposure to bretylium potentiated responses to phenylephrine in normal atria but not after 6-hydroxydopamine pretreatment. The results obtained indicate that the contribution of the indirect component of action to the pharmacological effects of phenylephrine is negligible in the normal tissue because a large fraction of the norepinephrine released by phenylephrine leaves the nerve endings as inactive metabolites. Inhibition of monoamine oxidase unmasks the indirect component of action in these amines by preventing intraneuronal deamination of the released transmitter. Consequently, while phenylephrine acts predominantly as a direct agent in the normal tissue, it behaves as an amine with mixed effects after inhibition of monoamine oxidase. It is concluded that the failure of reserpine pretreatment to modify responses to sympathomimetic amines does not exclude the possibility that the amine might release endogenous norepinephrine. © 1974 by The Williams & Wilkins Co.