Evidence for a Dual Effect of γ-Aminobutyric Acid on Thyrotropin (TSH)-Releasing Hormone-Induced TSH Release from Perifused Rat Pituitaries*

The effects of 7-aminobutyric acid (GABA) on the spontaneous and TRH-induced TSH release were investigated in vitro on perifused rat pituitaries. The dynamic pattern of TSH release was measured in response to a 6-min pulse of TRH (10 nM) with or without GABA addition. GABA had no effect on spontaneous TSH release but exhibited a dual effect on TSH-stimulated release according to the dose (as calculated by the induced-basal ratio): a potentiation of the TSH response to TRH at the lowest concentrations tested (≤10 nM) and an inhibition for GABA concentrations equal or higher than 100 nM. The GABA potentiation was mimicked by muscimol (10 nM) and isoguvacine (10 nM) but not by baclofen (1 μM). Bicucullin (1 μM) or picrotoxin (1 μM) added 15 min before GABA was unable to reverse the GABA potentiation of the TSH response, although SR 95103 (1 and 10 μM), a specific GABA A antagonist, partially or totally antagonized this response. Diazepam (7 nM) was able to potentiate the TSH response by 216% when GABA was ad...