Nobuo Aikawa, Akira Karasawa and Kenji Ohmori
Drug Development Research Laboratories, Pharmaceutical Research Institute,
Kyowa Hakko Kogyo Co., Ltd.,
1188 Shimotogari, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8731, Japan
Abstract: The effect of zaldaride, a calmodulin inhibitor, on
16,16-dimethyl prostaglandinﾊE2 (dmPGE2)-induced intestinal
ion secretion was investigated in rats. Zaldaride inhibited the dmPGE2-induced
increase in water content in the colon, but not that in the small intestine.
In the colonic mucosa, zaldaride attenuated the dmPGE2-induced
short-circuit current; however, it did not affect the forskolin or dibutyryl
cAMP-induced effect. These results suggest that zaldaride inhibits dmPGE2-induced
intestinal ion secretion by reducing the activity of Ca2+/calmodulin-dependent
adenylate cyclase linked to a receptor, and the colon may be an important
site in the action of zaldaride.
Keywords: Zaldaride maleate, Calmodulin, Intestinal secretion