Thyrotropin-releasing hormone in the dorsal vagal complex stimulates pancreatic blood flow in rats.
Central administration of thyrotropin-releasing hormone (TRH) enhanced pancreatic blood flow in animal models. TRH nerve fibers and receptors are localized in the dorsal vagal complex (DVC), and retrograde tracing techniques have shown that pancreatic vagal nerves arise from the DVC. However, nothing is known about the central sites of action for TRH to elicit the stimulation of pancreatic blood flow. Effect of microinjection of a TRH analog into the DVC on pancreatic blood flow was investigated in urethane-anesthetized rats. After measuring basal flow, a stable TRH analog (RX-77368) was microinjected into the DVC and pancreatic blood flow response was observed for 120 min by laser Doppler flowmetry. Vagotomy of the several portions, or pretreatment with atoropine methyl nitrate or N(G)-nitro-l-arginine-methyl ester was performed. Microinjection of RX-77368 (0.1-10 ng) into the left or right DVC dose-dependently increased pancreatic blood flow. The stimulation of pancreatic blood flow by RX-77368 microinjection was eliminated by the same side of cervical vagotomy as the microinjection site or subdiaphragmatic vagotomy, but not by the other side of cervical vagotomy. The TRH-induced stimulation of pancreatic blood flow was abolished by atropine or N(G)-nitro-l-arginine-methyl ester. These results suggest that TRH acts in the DVC to stimulate pancreatic blood flow through vagal-cholinergic and nitric oxide dependent pathways, indicating that neuropeptides may act in the specific brain nuclei to regulate pancreatic function.
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
Yokohama
Shiro
S
Kono
Toru
T
Tanamo
Masaya
M
Shimada
Tadahito
T
Hiraishi
Hideyuki
H
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017078:Laser-Doppler Flowmetry; D008297:Male; D008526:Medulla Oblongata / Q000033:anatomy & histology*; D008845:Microinjections; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010179:Pancreas / Q000098:blood supply*; D010276:Parasympatholytics / Q000494:pharmacology; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D013973:Thyrotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D014628:Vagotomy; D014630:Vagus Nerve / Q000378:metabolism*
D004791:Enzyme Inhibitors; D010276:Parasympatholytics; D013973:Thyrotropin-Releasing Hormone; C027979:L-pyroglutamyl-L-histidyl-3,3-dimethylprolinamide; D001285:Atropine; D011761:Pyrrolidonecarboxylic Acid; D019331:NG-Nitroarginine Methyl Ester