title: Acetylcholine triggers L-glutamate exocytosis via nicotinic receptors and inhibits melatonin synthesis in rat pinealocytes.
abstract: Rat pinealocytes, melatonin-secreting endocrine cells, contain peripheral glutaminergic systems. L-Glutamate is a negative regulator of melatonin synthesis through a metabotropic receptor-mediated inhibitory cAMP cascade. Previously, we reported that depolarization of pinealocytes by externally added KCl and activation of L-type Ca2+ channels resulted in secretion of L-glutamate by microvesicle exocytosis. What is unknown is how and what kinds of stimuli trigger glutamate exocytosis under physiological conditions. Here, we report that the nicotinic acetylcholine receptor can trigger glutamate exocytosis from cultured rat pinealocytes. Moreover, acetylcholine or nicotine inhibited norepinephrine-dependent serotonin N-acetyltransferase activity, which results in decreased melatonin synthesis. These activities were blocked by (2S,3S, 4S)-2-methyl-2-(carboxycyclopropyl)glycine, an antagonist of the metabotropic glutamate receptor. These results suggest that cholinergic stimulation initiates the glutaminergic signaling cascade in pineal glands and that parasympathetic neurons innervating the gland exert negative control over melatonin synthesis by way of the glutaminergic systems.
authors.affiliation: Department of Cell Membrane Biology, Institute of Scientific and Industrial Research (ISIR), Osaka University, Ibaraki, Osaka 567, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yamada
authors.forename: A
authors.initials: A
authors.lastname: Ogura
authors.forename: S
authors.initials: S
authors.lastname: Koizumi
authors.forename: A
authors.initials: A
authors.lastname: Yamaguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Moriyama
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000378:metabolism; D001285:Atropine / Q000494:pharmacology; D002038:Bungarotoxins / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology; D020746:Calcium Channels, L-Type; D002217:Carbachol / Q000494:pharmacology; D002478:Cells, Cultured; D004110:Diltiazem / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism*; D008550:Melatonin / Q000096:biosynthesis*; D009116:Muscarine / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D009568:Nitrendipine / Q000494:pharmacology; D010095:Oxotremorine / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000502:physiology; D010870:Pineal Gland / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000502:physiology*; D012601:Scopolamine / Q000494:pharmacology; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism; D014403:Tubocurarine / Q000494:pharmacology
chemical_list: D002038:Bungarotoxins; D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D018698:Glutamic Acid; D010095:Oxotremorine; D009538:Nicotine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D001285:Atropine; D009116:Muscarine; D002217:Carbachol; D009568:Nitrendipine; D012601:Scopolamine; D001191:Arylamine N-Acetyltransferase; D004110:Diltiazem; D009543:Nifedipine; D008550:Melatonin; D000109:Acetylcholine; D002118:Calcium; D014403:Tubocurarine