Thyrotropin-release hormone (TRH) attenuates glutamate-stimulated increases in calcium in primary neuronal cultures

Thyrotropin-releasing hormone (TRH) has been found to be widely distributed in the mammalian central nervous system. Further, the concentration of the tripeptide increases following seizure activity, and TRH is known to have anticonvulsant effects. We have investigated the possibility that the anticonvulsant activity of TRH may be due, at least in part, to an attenuation of the glutamate-stimulated increases in intraneuronal Ca²⁺ (Ca]_i) that occur with epileptic activity. We find that the tripeptide does not itself excite neurons and that it is able to significantly reduce glutamate-stimulated increases in Ca]_i in cultured neurons derived from fetal rat forebrain. Increases in the concentration of TRH following seizure activity may represent an endogenous homeostatic mechanism for reducing glutamate-induced elevations in intraneuronal Ca²⁺.