Effect of TA-0910, a Novel Thyrotropin-Releasing Hormone Analog, on In Vivo Acetylcholine Release and Turnover in Rat Brain.

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To examine the action of a novel thyrotropin-releasing hormone (TRH) analog, TA-0910 ((−)-N-[(S)-hexahydro-l-methyl-2, 6-dioxo-4-pyrimidinylcarbonyl]-L histidyl-L prolinamide tetrahydrate), on the cerebral cholinergic systems, the release of acetylcholine (ACh) and choline in freely-moving rats and ACh accumulation in gamma-butyrolactone (GBL, a nerve impulse flow blocker) and physostigmine-treated rats were examined. TA-0910 (0.1—1 mg/kg, i.p.) caused a marked dose-dependent increase in extracellular ACh levels and a decrease in choline levels in the hippocampus of freely moving rats. These effects were significantly stronger and longer-lasting than similar effects of TRH. TA-0910 (1, 3 mg/kg, i.p.) depressed the ACh accumulation in the cerebral cortex and hippocampus of GBL (1000 mg/kg, i.p.)-treated rats. Moreover, this analog (1, 3 mg/kg, i.p.) increased the accumulation rate of ACh in these regions in physostigmine (1 mg/kg, i.p.)-treated rats. TRH (30 mg/kg, i.p.) affected the ACh accumulation only in the hippocampus of the GBL-treated rats. These results suggest that TA-0910 not only enhances the release of ACh, but also accelerates the ACh turnover, i.e., ACh release and synthesis, at the cholinergic neuronal terminals in normal rats.

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  • Jpn.J.Pharmacol.

    Jpn.J.Pharmacol. 71 (2), 139-145, 1996

    公益社団法人 日本薬理学会

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