MODULATION OF PERIPHERAL ADRENERGIC NEUROTRANSMISSION BY METHIONINE-ENKEPHALIN

Abstract

The isolated perfused cat spleen prelabeled with [3H]norepinephrine [NE] was used to study the effects of morphine and metenkephalin on the exocytotic release of NE from sympathetic adrenergic neurons after nerve stimulation. The overflow of endogenous NE, total 3H and dopamine-.beta.-dydroxylase (DBH) from cat spleens was measured during postganglionic stimulation of the splenic nerve. Perfusion of spleens with metenkephalin (10-8-10-5M) produced a dose-dependent decrease in the release of endogenous NE upon nerve stimulation. These changes were paralleled by significant dose-dependent metenkephalin-induced decreases in the nerve stimulation-mediated release of total 3H, DBH and in the perfusion pressure. Perfusion of spleens with morphine (10-7-10-4 M) produced no significant changes in the release of endogenous NE, total 3H or DBH after nerve stimulation at 5 Hz. Morphine (10-7-10-4 M) 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 NE, total 3H, DBH or perfusion pressure. Perfusion with naloxone (10-6 M) plus metenkephalin (10-6-10-5 M) antagonized the inhibitory effects of metenkephalin. The opiate receptor population in peripheral tissues are apparently heterogenous and metenkephalin when depress exocytotic release of NE by interacting with a speciic presynaptic opiate receptor.