title: Stimulation of melatonin synthesis in ovine pineals in vitro.
abstract: Static and superfused pineal slices (750 micron) have been used to study the control of melatonin synthesis by ovine pineals. Static incubates show a time-dependent accumulation of melatonin in the medium; this is significantly increased by stimulation with norepinephrine (NE) (10(-5) M), reaching 300% above control levels after 4 h. Perifused pineal slices show a rapid rise in melatonin release within 12-18 min in response to NE stimulation. This reaches a 3.5-4.5-fold increase in melatonin released within 30 min. Withdrawal of NE is associated with a rapid return to prestimulated levels within 12-18 min. These time-course characteristics compare favorably to those changes seen in vivo. The formation of [14C]melatonin from [14C]-tryptophan shows a linear increase with time. In the presence of NE (10(-5) M), the rate of synthesis is increased, albeit after an initial time lag of at least 30 min. The latter may reflect an N-acetyltransferase-independent mechanism of synthesis and release. In static incubations, propranolol (10(-5) M) inhibited NE-induced melatonin production by about 60%, but prazosin (10(-5) M) had no effect. As dibutyryl cyclic AMP (10(-3) M) stimulated melatonin production, it is concluded that beta-receptors are of primary importance to the control of melatonin production, as in the rat. The role of alpha 1-receptors is less clear, but the stimulatory action of phorbol 12-myristate 13-acetate on melatonin release implicates a receptor linked to phosphatidylinositol turnover.
authors.affiliation: Rowett Research Institute, Bucksburn, Aberdeen, Scotland.
authors.forename: P J
authors.initials: PJ
authors.lastname: Morgan
authors.forename: L M
authors.initials: LM
authors.lastname: Williams
authors.forename: W
authors.initials: W
authors.lastname: Lawson
authors.forename: G
authors.initials: G
authors.lastname: Riddoch
mesh_terms: D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D007700:Kinetics; D008550:Melatonin / Q000096:biosynthesis*; D009478:Neuropeptide Y / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010477:Perfusion; D010870:Pineal Gland / Q000187:drug effects / Q000378:metabolism*; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology; D012756:Sheep; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014364:Tryptophan / Q000378:metabolism
chemical_list: D009478:Neuropeptide Y; D011943:Receptors, Adrenergic, beta; D000001:Calcimycin; D003994:Bucladesine; D014364:Tryptophan; D011433:Propranolol; D008550:Melatonin; D013755:Tetradecanoylphorbol Acetate; D009638:Norepinephrine; D011224:Prazosin