Cisplatin-induced inhibition of the calcium-calmodulin complex, neuronal nitric oxide synthase activation and their role in stomach distention.
Cisplatin (8 mg/kg; i.p.) treatment of Wistar rats produced no change in nitric oxide synthase (NOS) localization or its intensity for up to 5 days. However, immunohistochemically the levels of L-citrulline and the Ca(2+)-calmodulin complex were decreased after only 3 days. An in vitro experiment using an analog of calmodulin. Mero-Calmodulin-1, showed that cis-diammine-diaquacisplatinum(II), a hydrolyzed form of cisplatin, inhibited the calmodulin conformational shift from occurring through a direct interaction with the calmodulin molecule. The results indicate that distention of the stomach was due to inhibition of neuronal NOS activation by a direct interaction between cisplatin and the calcium binding sites of the calmodulin molecule.
Jarve
R K
RK
Department of Zoology, Michigan State University, East Lansing 48824-1115, USA.
Aggarwal
S K
SK
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism*; D002945:Cisplatin / Q000494:pharmacology*; D002956:Citrulline / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects* / Q000201:enzymology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000187:drug effects* / Q000201:enzymology
D000970:Antineoplastic Agents; D002147:Calmodulin; D002956:Citrulline; D019001:Nitric Oxide Synthase; D002945:Cisplatin; D002118:Calcium