title: Parasympathetic inhibition of pineal indole metabolism by prejunctional modulation of noradrenaline release.
abstract: The role of the parasympathetic nervous system in rat pineal indole metabolism was investigated by transpineal in vivo microdialysis. On-line coupling to a high performance liquid chromatography system with fluorescence detection (HPLC-FD) allowed simultaneous analysis of three major indolic compounds from the pineal, i.e. serotonin, N-acetylserotonin and melatonin. Infusion of the muscarinic receptor agonists, carbachol and oxotremorine, during the dark period resulted in a marked decrease of melatonin release. This effect was suggested to be mediated by a decrease in N-acetyltransferase activity, since a similar decrease was seen in N-acetylserotonin release, while serotonin levels increased simultaneously. Nicotine did show a very slight effect on the three indoles under these circumstances. Neostigmine failed to influence pineal indole metabolism, indicating that the endogenous tonus of acetylcholine release is either absent or extremely low in the middle of the dark period. The involvement of sympathetic innervation in the muscarinic effects was investigated by measurement of noradrenaline release from the pineal by sensitive off-line HPLC-FD analysis of noradrenaline in the dialysates. Carbachol markedly decreased the noradrenaline input during the infusion. Noradrenaline release returned to baseline values immediately after infusion with carbachol. These data suggest that the in vivo inhibitory effect of muscarinic receptor agonists on pineal melatonin production is mediated by presynaptic muscarinic receptors, located on the sympathetic nerve endings. This prejunctional inhibition of noradrenaline release causes a reduced induction of N-acetyltransferase activity, resulting in decreased melatonin release.
authors.affiliation: University Centre for Pharmacy, Department of Medicinal Chemistry, Groningen, Netherlands. wjd@farm.rug.nl
authors.forename: W J
authors.initials: WJ
authors.lastname: Drijfhout
authors.forename: C J
authors.initials: CJ
authors.lastname: Grol
authors.forename: B H
authors.initials: BH
authors.lastname: Westerink
mesh_terms: D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D018679:Cholinergic Agonists / Q000494:pharmacology*; D008297:Male; D008550:Melatonin / Q000378:metabolism; D017551:Microdialysis; D009538:Nicotine / Q000494:pharmacology; D009638:Norepinephrine / Q000032:analysis*; D010095:Oxotremorine / Q000494:pharmacology; D010870:Pineal Gland / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D012701:Serotonin / Q000378:metabolism; D014363:Tryptamines / Q000378:metabolism*
chemical_list: D018679:Cholinergic Agonists; D014363:Tryptamines; D012701:Serotonin; D010095:Oxotremorine; D009538:Nicotine; D002217:Carbachol; D008550:Melatonin; D009638:Norepinephrine