Thyrotropin-releasing hormone (TRH): Action mechanism of an enhanced dopamine release from rat striatal slices

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Abstract
The enhancing effect of TRH [thyrotropin releasing hormone] on dopamine (DA) release from rat striatal slices was investigated in relation to Ca2+ and cholinergic mechanisms. TRH(10-5 .apprx. 10-3 M) facilitated concentration dependently the uptake of 14C-DA by rat striatal slices, while methamphetamine (10-6 .apprx. 10-4 M) exhibited a considerable inhibitory effect. TRH (10-7 .apprx. 10-3 M) alone did not increase the DA release into the incubation medium, but it enhanced the DA release in the concomitant presence of desipramine (5 .times. 10-5 M). In the superfusion study, TRH (10-5 .apprx. 10-3 M), methamphetamine (10-6 .apprx. 10-4 M) and KCl (2.5 .apprx. 5.0 .times. 10-2 M) enhanced the DA release into the perfusion fluid. The DA releasing effect of TRH was completely blocked by cholinergic blockers (scopolamine, hexamethonium and hemicholinium), Ca2+ chelator (EGTA, ethylene glycol bis (.beta.-aminoethyl ether) N,N''-tetraacetic acid), Ca2+ antagonist (CoCl2) and Ca2+ influx blocker (D-600, .alpha.-isopropyl-.alpha.[N-methyl-N-homoveratryl)-.gamma.-aminopropyl]-3,4,5-trimethoxyphenylacetonitrile hydrochloride or by the removal of Ca2+ from the medium. The methamphetamine-enhanced DA release was not modified by the above treatments except for a partial decline produced by EGTA coupled with the removal of Ca2+. TRH(10-4 M) also facilitated the uptake of 3H-norepinephrine (NE) by rat cerebral cortex slices, but methamphetamine (10-6 .apprx. 10-4 M) exhibited a considerable inhibitory effect. In the superfusion study, TRH (10-5 .apprx. 10-4 M) and methamphetamine (10-7 .apprx. 10-4 M) enhanced NE release into the perfusion fluid. TRH facilitated DA release from rat striatal slices by mediating through a cholinergic mechanism and by enhancing the influx of Ca2+.