Involvement of glutamate and gamma-aminobutyric acid (GABA)-ergic systems in thyrotropin-releasing hormone-induced rat cerebellar cGMP formation.
The increase in cyclic guanosine 3',5'-monophosphate (cGMP) caused by subcutaneous injection of thyrotropin-releasing hormone (TRH) tartrate was observed in a region-specific manner in the rat cerebellum. TRH tartrate (TRH-T) (2.8, 7.0 and 17 mg/kg as free TRH, s.c.) produced dose-dependent increases in cGMP levels markedly in the cerebellar superior and inferior vermis, and a smaller but still significant increase in the cerebellar hemispheres and brainstem but no significant increases in other brain regions. The TRH-induced increase in the cGMP level in the cerebellum was suppressed by pretreatment with muscimol, THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3(2H)-one) or MK-801 (dizocilpine maleate) and partially suppressed by atropine but was not suppressed by chlordiazepoxide, oxazepam, phentolamine, propranolol, cyproheptadine, haloperidol, baclofen or DNQX (6,7-dinitroquinoxaline-2,3-dione), suggesting the possible involvement of GABA (gamma-aminobutyric acid)(A)-ergic, N-methyl-D-aspartate (NMDA)-type glutamatergic and cholinergic systems. These results suggest that excitatory amino acids may be involved in the cGMP formation caused by TRH in the cerebellar areas, and that cGMP formation is inhibited by enhancement of GABAA receptor function.
Nakayama
T
T
Pharmaceutical Research Laboratories I, Takeda Chemical Industries, Ltd., Osaka, Japan. Nakayama_Takahiro@takeda.co.jp
Hashimoto
T
T
Nagai
Y
Y
D000818:Animals; D002531:Cerebellum / Q000187:drug effects*; D006152:Cyclic GMP / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D013973:Thyrotropin-Releasing Hormone; D016291:Dizocilpine Maleate; D006152:Cyclic GMP