Peptidergic modulation of serotonin release from cultured rat pinealocytes.
This paper describes the effects of beta-adrenergic and peptidergic inputs on serotonin (5-HT) synthesis, outflow and metabolism into melatonin in cultured dissociated rat pinealocytes. The spontaneous outflow of 5-HT from pinealocytes was high as demonstrated by the elevated levels of extracellular 5-HT accumulated in the medium (about 5 ng/h/70,000 pineal cells). The beta-adrenergic agonist isoproterenol (ISO) used at concentrations up to 10(-6) M induced a moderate (+20-40%) increase in intra- and extracellular 5-HT levels together with a large release of melatonin. At a higher ISO stimulation (10(-5) M), the intra- and extracellular levels of 5-HT were significantly (-25-30%) reduced whereas melatonin secretion was dramatically increased. This is interpreted as a large 5-HT mobilization for melatonin synthesis and release, consequently reducing both the intracellular pool and outflow of 5-HT. The peptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating peptide (PACAP) up to 10(-7) M induced always a moderate (+20-30%) increase in intra- and extracellular levels of 5-HT. However, the use of nM concentrations of VIP or PACAP together with 10(-6) M ISO induced a decrease in 5-HT outflow (-25-30%) and a dramatic increase in melatonin secretion as did 10(-5) M ISO alone. Neuropeptide Y (NPY) is another pineal peptide which induced a stimulation of 5-HT outflow (+30-40%) although its effect on melatonin release was marginal. The above results are discussed in term of the multineuronal regulation of the synthetic and secretory activities of the rat pineal gland.
Simonneaux
V
V
Neurobiologie des Fonctions Rythmiques et Saisonnières, URA-CNRS 1332, Université Louis Pasteur, 12 rue de l'Université, 67000 Strasbourg, France.
Miguez
J M
JM
Pevet
P
P
D000818:Animals; D002478:Cells, Cultured; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology; D009479:Neuropeptides / Q000494:pharmacology; D010870:Pineal Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000494:pharmacology*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
C495403:Adcyap1 protein, rat; D009478:Neuropeptide Y; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012701:Serotonin; D014660:Vasoactive Intestinal Peptide; D007545:Isoproterenol