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.
D000818:Animals; D002415:Cats; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism; D004558:Electric Stimulation; D004723:Endorphins / Q000494:pharmacology*; D004744:Enkephalin, Methionine; D004745:Enkephalins / Q000494:pharmacology*; D005260:Female; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010525:Peripheral Nerves / Q000187:drug effects; D011957:Receptors, Opioid / Q000187:drug effects; D013154:Spleen / Q000294:innervation; D013564:Sympathetic Nervous System / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*
D004723:Endorphins; D004745:Enkephalins; D011957:Receptors, Opioid; D009270:Naloxone; D004744:Enkephalin, Methionine; D009020:Morphine; D004299:Dopamine beta-Hydroxylase; D009638:Norepinephrine