[Thyrotropin-releasing hormone (TRH): action mechanism of an enhanced dopamine release from rat striatal slices (author's transl)].
The enhancing effect of TRH on dopamine(DA) release from rat striatal slices was investigated in relation to Ca2+ and cholinergic mechanisms. TRH(10(-5)--10(-3) M) facilitated concentration dependently the uptake of 14C-DA by rat striatal slices, while methamphetamine (10(-6)--10(-4)M) exhibited a considerable inhibitory effect. TRH (10(-7)--10(--3)M) alone did not increase the DA release into the incubation medium, but it clearly enhanced the DA release in the concomitant presence of desipramine (5 x 10(-5)M). In the superfusion study, TRH (10(-5)--10(-3)M), methamphetamine (10(-6)--10(-4)M) and KCl (2.5--5.0 x 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), Ca2+ antagonist(CoCl2) and Ca2+ influx blocker(D-600) or by the removal of Ca2+ from the medium. The methamphetamine-enhanced DA release, however, 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 norepinephrine (NE) by rat cerebral cortex slices, but methamphetamine (10-(6)--10(-4)M) exhibited a considerable inhibitory effect. In the superfusion study, TRH (10(-5)--10(-4)M) and methamphetamine (10(-7)--10(-4)M) enhanced the NE release into the perfusion fluid. Therefore, it can be concluded that TRH facilitated the DA release from rat striatal slices by mediating through a cholinergic mechanism and enhancing the influx of Ca2+.
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology; D002540:Cerebral Cortex / Q000378:metabolism; D003035:Cobalt / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004533:Egtazic Acid / Q000494:pharmacology; D005711:Gallopamil / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D010277:Parasympathomimetics / Q000494:pharmacology; D010477:Perfusion; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D013268:Stimulation, Chemical; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D000596:Amino Acids; D010277:Parasympathomimetics; D005711:Gallopamil; D003035:Cobalt; D008694:Methamphetamine; D004533:Egtazic Acid; D005680:gamma-Aminobutyric Acid; D013973:Thyrotropin-Releasing Hormone; D011189:Potassium Chloride; D002118:Calcium; D004298:Dopamine; D009638:Norepinephrine