Protective effect of central thyrotropin-releasing hormone analog on cerulein-induced acute pancreatitis in rats.
Central neuropeptides play a role in many physiological functions through the autonomic nervous system. We have recently demonstrated that central injection of a thyrotropin-releasing hormone (TRH) analog increases pancreatic blood flow through vagal and nitric oxide-dependent pathways. In this study, the central effect of a TRH analog on experimental acute pancreatitis was investigated in rats. Acute pancreatitis was induced by two intraperitoneal injections of cerulein (40 microg/kg) at 1-h interval. Either stable TRH analog, RX 77368 (5-100 ng), or saline was injected intracisternally 15 min before the first cerulein injection under ether anesthesia. Serum amylase level was measured before and 5 h after the first cerulein injection. Pancreatic wet/dry weight ratio and histological changes were also evaluated. Intracisternal TRH analog inhibited cerulean-induced elevation of serum amylase level, increase in pancreatic wet/dry weight ratio and pancreatic histological changes, such as interstitial edema, inflammation and vacuolization. The pancreatic cytoprotection induced by central TRH analog was abolished by subdiaphragmatic vagotomy and N(G)-nitro-L-arginine-methyl ester (L-NAME), but not by 6-hydroxydopamine (6-OHDA). Intravenous administration of the TRH analog did not influence cerulein-induced acute pancreatitis. These results indicate that the TRH analog acts in the central nervous system to protect against acute pancreatitis through vagal and nitric oxide-dependent pathways.
Yoneda
Masashi
M
Department of Gastroenterology, Dokkyo University School of Medicine Kitakobayashi 880, Mibu, Tochigi 321-0293, Japan. yoneda@dokkyomed.ac.jp
Goto
Manabu
M
Nakamura
Kimihide
K
Shimada
Tadahito
T
Hiraishi
Hideyuki
H
Terano
Akira
A
Haneda
Masakazu
M
D018663:Adrenergic Agents / Q000494:pharmacology; D000681:Amylases / Q000097:blood; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects; D002108:Ceruletide / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004487:Edema; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009479:Neuropeptides / Q000737:chemistry*; D009569:Nitric Oxide / Q000378:metabolism; D016627:Oxidopamine / Q000494:pharmacology; D010179:Pancreas / Q000378:metabolism*; D010195:Pancreatitis / Q000188:drug therapy*; D010455:Peptides / Q000737:chemistry; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013997:Time Factors
D018663:Adrenergic Agents; D004791:Enzyme Inhibitors; D009479:Neuropeptides; D010455:Peptides; D009569:Nitric Oxide; D013973:Thyrotropin-Releasing Hormone; C027979:L-pyroglutamyl-L-histidyl-3,3-dimethylprolinamide; D002108:Ceruletide; D016627:Oxidopamine; D000681:Amylases; D011761:Pyrrolidonecarboxylic Acid; D019331:NG-Nitroarginine Methyl Ester