Molecular mechanisms controlling norepinephrine-mediated release of serotonin from rat pineal glands

This study describes various elements of the mechanism controlling norepinephrine (NE)-mediated release of serotonin (5HT) from rat pineal glands. After radiolabelling the endogenous pool of pineal 5HT with 3H-5HT, individual pineal glands were exposed to depolarizing buffers or those containing NE. Although 3H-5HT was not released by 50mM potassium, efflux of the indoleamine was increased by NE. Alpha-adrenergic receptors mediate the effects of NE as indicated by the fact that phenylephrine but not isoproterenol, a beta receptor agonist, also enhanced 3H-5HT release. This hypothesis is supported further by the fact that prazosin and phentolamine (alpha-antagonists) but not sotolal (beta-antagonist), inhibited the stimulatory effects of NE on 5HT release. In order to determine the intracellular second messenger involved in the 5HT release process, pineals were incubated with 8-bromo cAMP or the phorbol ester, PMA. PMA simulated the effects of NE and phenylephrine on 3H-5HT efflux, while cAMP had no effect. Furthermore, calcium-, phospholipid-dependent protein kinase activities in pineal homogenates were responsive to NE. These findings suggest that 5HT secretion from rat pinealocytes occurs rapidly in response to NE signals that act through alpha-adrenergic receptors in concert with phospholipid dependent protein kinase(s). These molecular processes are different from those involved in melatonin metabolism and may represent a general mechanism for regulating 5HT release in the brain.