Involvement of dihydropyridine-sensitive calcium channels In the GABA A potentiation of TAH-induced TSH release

Abstract

The effects of γ-aminobutyric acid (GABA) and isoguvacine on the thyrotropin (TSH) secretion stimulated by thyrotropin releasing hormone (TRH), were investigated in vitro with perifused rat pituitaries. At nanomolar concentrations the two agonists induced potentiation of the TRH-induced TSH release. The potentiation was blocked by SR 95531 a specific GABA A antagonist. The isoguvacine potentiation of the TSH response to TRH failed to occur when cobalt (Co 2+) was added to the perifused medium. Nifedipine completely blocked the GABA or isoguvacine potentiation of the TSH response while ω-conotoxin did not modify it. Pre-perifusion of the pituitaries with pertussis toxin did not change the TSH response to TRH but completely inhibited the isoguvacine potentiation of the response. Our results demonstrate that the GABA potentiation of TRH-induced TSH release occurring through the stimulation of GABA A receptor sites is a calcium (Ca 2+)-dependent phenomenon, probably mediated by activation of dihydropyridine (DHP)-sensitive, ω-conotoxin-insensitive Ca 2+ channels involving a pertussis toxin-sensitive G protein.