Effect of zaldaride maleate, an antidiarrheal compound, on intracellular cyclic nucleotide-mediated intestinal ion secretion in rats.
The purpose of this study is to clarify the mechanisms of action of zaldaride, a calmodulin inhibitor. 16,16-Dimethyl prostaglandin E(2), forskolin, 8-bromo cAMP, nitroprusside, 8-bromo cGMP and Escherichia coli heat-stable enterotoxin STa increased the short-circuit current in rat colonic mucosa. Zaldaride at >/=10 microM significantly attenuated the 16,16-dimethyl prostaglandin E(2) and Escherichia coli heat-stable enterotoxin STa-induced increase in short-circuit current; whereas it did not affect other secretagogues-induced effects. These results suggest that zaldaride inhibits the activation of Ca(2+)/calmodulin-sensitive adenylate cyclase or guanylate cyclase linked to a receptor.
Aikawa
N
N
Drug Development Research Laboratories, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd., 1188 Shimotogari, Nagaizumi-cho, Sunto-gun, Shizuoka, Japan.
Karasawa
A
A
Ohmori
K
K
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D000930:Antidiarrheals / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013779:Tetrodotoxin / Q000494:pharmacology
D000897:Anti-Ulcer Agents; D000930:Antidiarrheals; D001562:Benzimidazoles; D002147:Calmodulin; D004791:Enzyme Inhibitors; D007473:Ion Channels; C052087:CGS 9343B; D005576:Colforsin; C016276:8-bromocyclic GMP; D013779:Tetrodotoxin; D000242:Cyclic AMP; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP; D015064:16,16-Dimethylprostaglandin E2