EVIDENCE FOR A REGULATORY ROLE OF MELATONIN ON SEROTONIN RELEASE AND UPTAKE IN THE PINEAL-GLAND

Melatonin has been proposed to exert some regulatory actions within th e pineal gland itself. The present study examined the effect of melato nin on the release of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) from rat pineal glands by using an in vitro perifusion system . Melatonin induced a concentration-dependent stimulatory effect on 5- HT secretion from 10(-6) M to 10(-3) M. Maximal effects were obtained with melatonin 10(-3) M and concentrations lower than 10(-6) M were wi thout effect. The secretion of 5-HIAA was inhibited by melatonin 10(-3 ) and 10(-4) M, but it was increased when pineals were incubated with 10(-5) and 10(-6) M of melatonin. The indoleamine secretion was also s tudied on peripherally denervated rat pineal glands. Basal output of 5 -HT from these glands was increased when compared with those from cont rol rats. In contrast, the secretion of 5-HIAA was strongly reduced af ter removal of the sympathetic input to the pineal gland. Melatonin 10 (-3) M failed to stimulate 5-HT release from denervated pineal glands, although it inhibited 5-HIAA secretion. In contrast, melatonin 10(-5) M enhanced 5-HT release without altering 5-HIAA output. Fluoxetine, a 5-HT uptake inhibitor, produced similar effects than mM concentration s of melatonin on the indoleamine secretion from control pineal glands , but it had no effect on glands taken from peripherally denervated ra ts. These data suggest that mM concentrations of the pineal hormone ar e able to stimulate 5-HT release from the pinealocyte, while mM concen trations of melatonin increase extracellular 5-HT by inhibiting its re uptake in the adrenergic nerve endings. These findings are discussed i n relation to the possible role of melatonin regulating the intra- and extracellular availability of 5-HT in the pineal gland and its signif icance as an autocrine factor.