Direct inhibitory effect of adrenomedullin and guanylin on isolated caecal circular smooth muscle cells of guinea pig.
Smooth muscle cells isolated from the caecal circular smooth muscle layers of the guinea pig were used to determine whether adrenomedullin and guanylin can inhibit the contractile response produced by 10(-9) M cholecystokinin octapeptide (CCK-8). In addition, to elucidate each intracellular mechanisms, we examined the effects of an inhibitor of cAMP-dependent protein kinase, an inhibitor of particulate guanylate cyclase, and an inhibitor of soluble guanylate cyclase on the adrenomedullin- or guanylin-induced relaxation of the caecal circular smooth muscle cells. Both adrenomedullin and guanylin inhibited the contractile response produced by CCK-8 in a dose-dependent manner, with IC50 values of 0.12 nM and 2.4 pM, respectively. An inhibitor of cAMP-dependent protein kinase significantly inhibited the relaxation produced by adrenomedullin. In contrast, an inhibitor of particulate guanylate cyclase and an inhibitor of soluble guanylate cyclase did not have any significant effect on the relaxation produced by adrenomedullin. On the other hand, an inhibitor of particulate guanylate cyclase significantly inhibited the guanylin-induced relaxation, although an inhibitor of cAMP-dependent protein kinase and an inhibitor of soluble guanylate cyclase did not have any significant effect on the guanylin-induced relaxation. In this study, we first demonstrated the direct inhibitory effects of adrenomedullin via cAMP system and guanylin via particulate guanylate cyclase system on the isolated caecal circular smooth muscle cells.
Ochiai
T
T
The Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Chijiiwa
Y
Y
Motomura
Y
Y
Iwakiri
Y
Y
Nawata
H
H
D053607:Adrenomedullin; D000818:Animals; D002432:Cecum / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005768:Gastrointestinal Hormones; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects*; D045265:Natriuretic Peptides; D010455:Peptides / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D005768:Gastrointestinal Hormones; D045265:Natriuretic Peptides; D010455:Peptides; D014665:Vasodilator Agents; C072685:guanylin; D053607:Adrenomedullin