Direct inhibitory effect of corticotropin releasing hormone on isolated caecal circular smooth muscle cells of guinea pig via adenylate cyclase system.
Smooth muscle cells isolated separately from the caecal circular smooth muscle layer of the guinea pig were used to investigate whether corticotropin releasing hormone (CRH) can inhibit directly the contraction produced by cholecystokinin octapeptide (CCK-8). In addition, the role of adenylate cyclase and guanylate cyclase in the direct inhibitory effect of CRH was examined. CRH inhibited the contractile response produced by 10(-9)M CCK-8 in a concentration-dependent manner, with an IC50 value of 0.16nM. An inhibitor of particulate guanylate cyclase and an inhibitor of soluble guanylate cyclase had no significant effect of the relaxation produced by CRH. In contrast, an inhibitor of adenylate cyclase and an inhibitor of cAMP-dependent protein kinase significantly inhibited the relaxation produced by CRH. This is the first report demonstrating the direct inhibitory action of CRH on the isolated caecal smooth muscle cells via adenylate cyclase system.
Iwakiri
Y
Y
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Chijiiwa
Y
Y
Motomura
Y
Y
Akiho
H
H
Osame
M
M
Nawata
H
H
D000067956:Adenylyl Cyclase Inhibitors; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D002432:Cecum / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D012844:Sincalide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000067956:Adenylyl Cyclase Inhibitors; D000634:Aminoquinolines; D004791:Enzyme Inhibitors; D003346:Corticotropin-Releasing Hormone; C041715:6-anilino-5,8-quinolinedione; D006162:Guanylate Cyclase; D012844:Sincalide; D013755:Tetradecanoylphorbol Acetate