Modulation of peripheral adrenergic neurotransmission by methionine-enkephalin.

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.