PEPTIDERGIC MODULATION OF SEROTONIN RELEASE FROM CULTURED RAT PINEALOCYTES

This paper describes the effects of beta-adrenergic and peptidergic in puts on serotonin (5-HT) synthesis, outflow and metabolism into melato nin in cultured dissociated rat pinealocytes. The spontaneous outflow of 5-HT from pinealocytes was high as demonstrated by the elevated lev els of extracellular 5-HT accumulated in the medium (about 5 ng/h/70,0 00 pineal cells). The beta-adrenergic agonist isoproterenol (ISO) used at concentrations up to 10(-6) M induced a moderate (+20-40%) increas e in intra- and extracellular 5-HT levels together with a large releas e of melatonin. At a higher ISO stimulation (10(-5) M), the intra- and extracellular levels of 5-HT were significantly (-25-30%) reduced whe reas melatonin secretion was dramatically increased. This is interpret ed as a large 5-HT mobilization for melatonin synthesis and release, c onsequently reducing both the intracellular pool and outflow of 5-HT. The peptides vasoactive intestinal peptide (VIP) and pituitary adenyla te 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 dramat ic increase in melatonin secretion as did 10(-5) M ISO alone. Neuropep tide Y (NPY) is another pineal peptide which induced a stimulation of 5-HT outflow (+30-40%) although its effect on melatonin release was ma rginal. The above results are discussed in term of the multineuronal r egulation of the synthetic and secretory activities of the rat pineal gland.