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

Biochem Pharmacol. 2006 Jun 14;71(12):1705-10. doi: 10.1016/j.bcp.2006.03.014. Epub 2006 Mar 22.

Abstract

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 PRL secretion dose-dependently, while GABA-A receptor agonist, 100 microM muscimol, but not GABA-B receptor agonist, 100 microM baclofen, decreased the secretion. GABA-C receptor antagonist, 15 microM (1,2,5,6-tetrahydropyridin-4-yl) methylphosphinic acid (TPMPA), and GABA-A receptor antagonist, 100 microM 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 (rho1, rho2, rho3) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Calcium / metabolism
  • Cells, Cultured
  • DNA Primers
  • Enzyme-Linked Immunosorbent Assay
  • Male
  • Pituitary Gland, Anterior / cytology
  • Pituitary Gland, Anterior / drug effects*
  • Pituitary Gland, Anterior / metabolism
  • Prolactin / metabolism*
  • Rats
  • Rats, Wistar
  • Receptors, GABA / drug effects*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • DNA Primers
  • GABA-C receptor
  • Receptors, GABA
  • Prolactin
  • Calcium