Regulation of Melatonin Synthesis and Release:Paracrine Relationships in Mammalian Pineal Gland

The pineal gland is regulated primarily by photoperiodic information attaining the organ through a polysynaptic pathway initiated in the retina. The sympathetic innervation to the pineal gland plays a major role in controlling phasic melatonin and serotonin (5HT) release. Additionally central pinealopetal fibers participate in pineal control; these fibers contain several neuropeptides and possibly amino acids and biogenic amines. Norepinephrine (NE) by acting on s1-and α1-adrenoceptors regulates melatonin synthesis, and by acting on αi-adrenoceptors increases 5HT release. Dopamine, by acting on D2 receptors, augments 5HT release in bovine pineals. By employing radioligand binding techniques several other neurotransmitter or neuromodulator acceptor sites have been described in mammalian pineal gland. They include, among others, the binding of glutamate, GABA (type A and B receptors), benzodiazepine (central-and peripheral-types), 5HT (S2), acetylcholine (muscarinic), substance P and VIP. The plurality of receptors suggests hitherto unrecognized paracrine relationships for a number of modulators in the mammalian pineal. As examples of these presumptive paracrine interrelations, GABA and 5HT were examined. The GABA synthesizing enzyme glutamic acid decarboxylase (GAD) is detectable in the pineal gland; in the bovine pineal GAD exhibits “neuronal-like” properties. By employing a specific antibody against GABA, a sub-population of pinealocytes gave a positive reaction. After a depolarizing stimulus, GABA is released from bovine and rat pineal glands by both Ca2+-dependent and Ca2+-independent processes. In the rat pineal GAGA is released by NE by acting through α1-adrenoceptors. GABA, by an effect mediated by type A receptors, impaired at physiological concentrations NE-induced melatonin release, while by acting on GABA type B receptors, decreased NE release. GABA augments38C1--influx and decreases depolarization-induced 45Ca2+ uptake in isolated bovine pineal cells. 5HT augments calcium uptake in bovine pinealocytes through an interaction with S2 receptor sites. This plurality of pineal control mechanisms is not dissimilar to that described for the adenohypophysis.