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Modulation of peripheral adrenergic neurotransmission by methionine- enkephalin

RR Gaddis and WR Dixon

The isolated perfusion cat spleen prelabeled with [3H]norepinephrine was used to study the effects of morphine and Met-enkephalin on the exocytotic release of norepinephrine from sympathetic adrenergic neurons after nerve stimulation. The overflow of endogenous norepinephrine, total 3H and dopamine-beta-hydroxylase (DBH) from cat spleens was measured during postganglionic stimulation of the splenic nerve. Perfusion of spleens with Met-enkephalin (10(-8)-10(-5) M) produced a dose-dependent decrease in the release of endogenous norepinephrine upon nerve stimulation. These changes were paralleled by significant dose-dependent Met-enkephalin-induced decreases in the nerve stimulation-mediated release of total 3H, DBH and in the perfusion pressure. However, perfusion of spleens with morphine (10(-7)- 10(-4) M) produced no significant changes in the release of endogenous norepinephrine, total 3H or DBH after nerve stimulation at 5 Hz. Morphine (10(-7)-10(-4) M) also had no significant effects on the contraction of the splenic capsule. Perfusion of spleens with naloxone (10(-6) M), a pure narcotic antagonist, did not alter the release of endogenous norepinephrine, total 3H, DBH or perfusion pressure. However, perfusion with naloxone (10(-6) M) plus Met-enkephalin (10(-6)- 10(-5) M) antagonized the inhibitory effects of Met-enkephalin. These findings support the hypothesis that the opiate receptor population in peripheral tissues are heterogenous and that Met-enkephalin depresses exocytotic release of norepinephrine by interacting with a specific presynaptic opiate receptor.

Volume 221, Issue 2, pp. 282-288, 05/01/1982
Copyright © 1982 by American Society for Pharmacology and Experimental Therapeutics




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Copyright © 1982 by the American Society for Pharmacology and Experimental Therapeutics.