γ-Aminobutyric acid (GABA)-C receptor stimulation increases prolactin (PRL) secretion in cultured rat anterior pituitary cells

gamma-Aminobutyric acid (GABA) reportedly inhibits secretion of anterior pituitary hormones by directly acting on GABA-A and GABA-B receptors on anterior pituitary cells, but the roles of GABA-C receptors are little known. In this study, involvement of GABA-C receptors in the secretion of prolactin (PRL) was examined using cultured rat anterior pituitary cells. GABA-C receptor agonist, cis-4-aminocrotonic acid (CACA, 0.1-1 mM) increased FRl secretion dose-dependently, while GABA-A receptor agonist, 100 mu M muscimol, but not GABA-B receptor agonist, 100 mu M baclofen, decreased the secretion. GABA-C receptor antagonist, 15 mu M (1,2,5,6-tetrahydropyridin-4-yl) methylphosphinic acid (TPMPA), and GABA-A receptor antagonist, 100 mu M bicuculline, not only reversed such an agonist-induced increase or decrease in PRL secretion, but also suppressed or enhanced spontaneous PRL secretion, raising a possibility of GABA-C or GABA-A receptor stimulation by intrinsic pituitary-derived GABA. GABA-C receptor subunits (p1, p2, p3) and GABA synthesizing enzymes (GAD 65 and GAD 67) were shown to be expressed as assayed by RT-PCR, and GABA-C receptor stimulation by CACA obviously increased intracellular Ca2+ concentration in the anterior pituitary cells. Thus, PRL secretion from anterior pituitary cells appears to be enhanced via direct GABA-C receptor stimulation by GABA originating from the anterior pituitary cells besides well-known hypothalamic GABA. (c) 2006 Elsevier Inc. All rights reserved.