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╩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