THYROTROPIN-RELEASING-HORMONE (TRH) ATTENUATES GLUTAMATE-STIMULATED INCREASES IN CALCIUM IN PRIMARY NEURONAL CULTURES

Thyrotropin-releasing hormone (TRH) has been found to be widely distri buted in the mammalian central nervous system. Further, the concentrat ion of the tripeptide increases following seizure activity, and TRH is known to have anticonvulsant effects. We have investigated the possib ility that the anticonvulsant activity of TRH may be due, at least in part, to an attenuation of the glutamate-stimulated increases in intra neuronal Ca2+ ([Ca](i)) that occur with epileptic activity. We find th at the tripeptide does not itself excite neurons and that it is able t o significantly reduce glutamate-stimulated increases in [Ca](i) in cu ltured neurons derived from fetal rat forebrain. Increases in the conc entration of TRH following seizure activity may represent an endogenou s homeostatic mechanism for reducing glutamate-induced elevations in i ntraneuronal Ca2+.