Nicotinic receptor stimulation activates enkephalin release and biosynthesis in adrenal chromaffin cells.
Neuroendocrine cells release a portion of their stored secretory hormone content when exposed to tissue-specific secretagogues. In the case of the adrenal medulla, catecholamines and enkephalin peptides, as well as other secretory proteins, are secreted in response to acetylcholine, which is released onto cholinergic receptors on chromaffin cells upon splanchnic nerve stimulation in vivo. Secretagogue stimulation thus depletes intracellular stores of exportable hormone. We were interested to know whether the signal for exportable hormone release might also function as a signal for compensatory hormone repletion by enhancing the biosynthesis of the released hormone(s). Accordingly, we have investigated the effect of nicotinic receptor stimulation on Met-enkephalin peptide biosynthesis and expression of proenkephalin messenger RNA in primary cultures of bovine chromaffin cells. Our results, reported here, suggest a model for stimulus-secretion-synthesis coupling in which nicotinic receptor occupancy activates two pathways. One pathway, dependent on calcium and not mimicked by increased intracellular cyclic AMP, leads to exocytotic hormone release; the other, probably via a calcium-dependent increase in intracellular cyclic AMP, leads to a compensatory increase in intracellular enkephalin through activation of transcription of the proenkephalin structural gene.
D000313:Adrenal Medulla / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D002837:Chromaffin Granules / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004744:Enkephalin, Methionine / Q000235:genetics; D004745:Enkephalins / Q000096:biosynthesis / Q000378:metabolism*; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D007700:Kinetics; D009538:Nicotine / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D011978:Receptors, Nicotinic / Q000502:physiology*
D004745:Enkephalins; D006584:Hexamethonium Compounds; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D018738:Hexamethonium; D004744:Enkephalin, Methionine; D009538:Nicotine; D000242:Cyclic AMP