Modulation by Leu-enkephalin of peptide release from perifused neurointermediate pituitary. II. Inhibition of calcium-mediated secretion of alpha-MSH and beta-endorphin.
The present study examines the effect of opiates on alpha-MSH and beta-endorphin release from perifused neurointermediate rat pituitaries, as stimulated by various secretagogues for which Ca ions and/or cAMP serve as messengers. alpha-MSH release stimulated by high K+ concentrations (5-min pulses) and veratridine depolarization, which is closely dependent on Ca2+ fluxes, was abolished by both Leu-enkephalin and beta-endorphin. A dose-response relationship between inhibition of alpha-MSH secretion and the concentration of Leu-enkephalin, with ED50 approximately 10(-9) M, was observed. High K+-induced release of beta-endorphin was likewise blunted by Leu-enkephalin. The stimulatory effect of the Ca2+ ionophore A 23187 was inhibited in a similar way as was that of CRF, which requires both Ca2+ fluxes and cAMP formation. The antagonist naloxone not only reversed the action of opiates, but also enhanced spontaneous hormonal output. In contrast, the effects of l-isoproterenol and forskolin, for which cAMP serves as a primary messenger, were unaffected in the absence of extracellular Ca ions and, also, in the presence of Leu-enkephalin. We conclude that opioid peptides may exert a direct inhibitory influence on the release of both alpha-MSH and beta-endorphin and do so by interfering with the Ca2+ messenger system. In addition, these data also suggest the existence of an opiate-opiate negative feedback mechanism.
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D005576:Colforsin / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D004723:Endorphins / Q000378:metabolism* / Q000494:pharmacology; D004743:Enkephalin, Leucine / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000378:metabolism*; D010904:Pituitary Gland, Posterior / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014701:Veratridine / Q000494:pharmacology; D001615:beta-Endorphin
D004723:Endorphins; D005576:Colforsin; D000001:Calcimycin; D004743:Enkephalin, Leucine; D001615:beta-Endorphin; D014701:Veratridine; D009074:Melanocyte-Stimulating Hormones; D003346:Corticotropin-Releasing Hormone; D007545:Isoproterenol; D011188:Potassium; D002118:Calcium