Evidence for a dual effect of gamma-aminobutyric acid on thyrotropin (TSH)-releasing hormone-induced TSH release from perifused rat pituitaries.
The effects of gamma-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 (less than or equal to 10 nM) and an inhibition for GABA concentrations equal or higher than 100 nM. The GABA potentiation was mimicked by muscimol (10 microM) and isoguvacine (10 nM) but not by baclofen (1 microM). Bicucullin (1 microM) or picrotoxin (1 microM) added 15 min before GABA was unable to reverse the GABA potentiation of the TSH response, although SR 95103 (1 and 10 microM), 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 added to the system at a concentration (60 nM) which does not modify by itself the TSH response. The inhibitory effect of GABA (100 nM) was completely abolished by bicucullin (1 microM), by picrotoxin (1 microM), and by SR 95103 (1 microM). Picrotoxin not only blocked the inhibitory action of GABA but significantly (P less than 0.05) potentiated the TSH response to TRH. Our data suggest a dual GABA-ergic control of TRH-stimulated TSH release directly on the pituitary, probably mediated by two different kinds of GABA receptors: a GABA A receptor site mediating the inhibitory effect and a nonclassical GABA A receptor site of higher affinity for its stimulatory action.
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D066298:In Vitro Techniques; D007539:Isonicotinic Acids / Q000494:pharmacology; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D010477:Perfusion; D010852:Picrotoxin / Q000494:pharmacology; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D011724:Pyridazines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013972:Thyrotropin / Q000378:metabolism*; D013973:Thyrotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D001640:Bicuculline; D007539:Isonicotinic Acids; D009118:Muscimol; D010852:Picrotoxin; D011724:Pyridazines; D013972:Thyrotropin; D013973:Thyrotropin-Releasing Hormone; D005680:gamma-Aminobutyric Acid; C044796:2-(carboxy-3'-propyl)-3-amino-4-methyl-6-phenylpyridazinium chloride; C015300:isoguvacine