Central thyrotropin-releasing hormone increases hepatic cyclic AMP through vagal-cholinergic and prostaglandin-dependent pathways in rats.
Central neuropeptides play roles in many physiologic regulations through the autonomic nervous system. We have demonstrated that central thyrotropin-releasing hormone (TRH), one of neuropeptides, induces a stimulation of hepatic proliferation through vagal-cholinergic pathways. Since cAMP is known to play an important role in the hepatic proliferation, effect of central TRH on hepatic cAMP was investigated. Rats were intracisternally injected with either a TRH analog, RX-77368 (1-100 ng), or saline. The liver was removed 2-72 h after the TRH analog and hepatic cAMP content was determined by radioimmunoassay. In some experiments, pretreatment with hepatic vagotomy, atropine methyl nitrate, or 6-hydroxydopamine (6-OHDA) was performed. Hepatic cAMP was dose-dependently increased by intracisternal TRH analog (5-100 ng) with a peak response occurring 12 h postinjection. The central TRH-induced increase in hepatic cAMP was abolished by vagotomy, atropine and indomethacin, but not by 6-OHDA. Intravenous injection of the TRH analog (10 ng) did not affect hepatic cAMP. These results demonstrate that TRH acts in the brain to increase hepatic cAMP through vagal-cholinergic and prostaglandin-dependent pathways, suggesting that central TRH modulates hepatic functions through cAMP-mediated signaling pathways.
Yoneda
Masashi
M
Department of Gastroenterology, Dokkyo University School of Medicine, Kitakobayashi 880, Mibu, Tochigi 321-0293, Japan. yoneda@dokkyomed.ac.jp
Kono
Toru
T
Watanobe
Hajime
H
Tamano
Masaya
M
Shimada
Tadahito
T
Hiraishi
Hideyuki
H
Nakamura
Kimihide
K
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002799:Cholinergic Fibers / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism*; D004247:DNA / Q000138:chemical synthesis; D004305:Dose-Response Relationship, Drug; D007213:Indomethacin / Q000494:pharmacology; D007276:Injections, Intraventricular; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D016627:Oxidopamine / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology*; D011761:Pyrrolidonecarboxylic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D013973:Thyrotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D014628:Vagotomy; D014630:Vagus Nerve / Q000502:physiology* / Q000601:surgery
D011453:Prostaglandins; D013973:Thyrotropin-Releasing Hormone; C027979:L-pyroglutamyl-L-histidyl-3,3-dimethylprolinamide; D001285:Atropine; D016627:Oxidopamine; D004247:DNA; D000242:Cyclic AMP; D011761:Pyrrolidonecarboxylic Acid; D007213:Indomethacin