Second messenger mechanisms governing opiate peptide transmitter regulation in the rat adrenal medulla.
Decreasing transsynaptic activity through surgical adrenal denervation or by medullary explantation, increases Leu-enkephalin immunoreactivity (Leu-Enk) and preproenkephalin mRNA (prepro-EK). Membrane depolarization prevents this rise. To determine whether depolarizing effects are mediated by intracellular movement of calcium ions, explanted medullae were depolarized in the presence of EGTA or the calcium ion 'channel' blockers D600 or verapamil. Inhibition of Ca2+ influx prevented the effects of KCl-induced depolarization on the rise in Leu-Enk and on prepro-EK. Increasing intracellular Ca2+ with the ionophore A23187, in the absence of depolarizing agents, reproduced the effects of depolarization. By contrast, medullae grown in the presence of A23187, but in Ca2+-free medium, showed similar increases in prepro-EK mRNA and Leu-Enk, indicating an absolute requirement for Ca2+. In addition, KCl-inhibitory effects could be partially blocked by the calmodulin and protein kinase-C antagonist, trifluoperazine. However, KCl effects were not antagonized by the preferential calmodulin inhibitors W7, W13 or calmidizolium even at doses 10-fold higher than required to prevent calmodulin-dependent effects. Thus, these data suggest that inhibitory effects of transsynaptic activity and membrane depolarization on adrenal enkephalin occurs through Ca2+ and perhaps through a protein kinase-C dependent pathway, mechanisms known to augment catecholamine biosynthesis. It appears then that the same or similar molecular mechanisms can result in differential regulation of these co-localized transmitter systems.
D000313:Adrenal Medulla / Q000502:physiology*; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004743:Enkephalin, Leucine / Q000235:genetics*; D004745:Enkephalins / Q000235:genetics*; D008297:Male; D009924:Organ Culture Techniques; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011498:Protein Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains; D014158:Transcription, Genetic / Q000187:drug effects; D014268:Trifluoperazine / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004745:Enkephalins; D011498:Protein Precursors; D012333:RNA, Messenger; D014268:Trifluoperazine; D000001:Calcimycin; D004743:Enkephalin, Leucine; C033660:preproenkephalin; D011493:Protein Kinase C; D002118:Calcium