GABA as a presumptive paracrine signal in the pineal gland. Evidence on an intrapineal GABAergic system

Abstract

GABA is present in the pineal gland of several mammals, where it is synthesized in situ as well as taken up from the circulation. This article reviews available information suggesting a local, physiological role of pineal GABA. Both the pinealocytes and the glial pineal cells have the capacity to take up GABA from the extracellular space. The GABA synthesizing enzyme glutamic decarboxylase (GAD) is detectable in the pineal gland; in the bovine pineal GAD exhibits “neuronal-like” properties. By employing a specific antibody against GABA, about 15% of pinealocytes gave a positive reaction in bovine pineal glands. After a depolarizing stimulus, GABA was released from bovine and rat pineal glands by both Ca 2+-dependent and Ca 2+-independent processes. By employing neuronal and glial GABA uptake inhibitors, most 3H-GABA release in bovine pineal gland could be attributed to a “neuronal” (presumably pinealocyte) compartment. Several components of the GABA type A receptor supramolecular complex (i.e., GABA binding sites, central-type benzodiazepine binding sites, Cl − ionophore), as well as a minor population of GABA type B receptor sites, were detected in bovine and human pineal glands. In the rat pineals, GABA is released by norepinephrine (NE) acting through alpha 1-adrenoceptors. Physiological concentrations of GABA, by its effect on type A receptor sites, impaired NE-induced melatonin release; by acting on GABA type B receptors, it decreased NE release. Another presumable presynaptic effect of GABA (i.e., to augment maximal velocity and to decrease affinity of NE uptake) was mediated by type A receptor sites. It is proposed that pre- and postsynaptic activity of GABA in the pineal does not differ from that found for GABA interneurons in local circuits of the brain.