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Cancer Chemother Pharmacol. 1997;39(4):341-8.

Cisplatin-induced inhibition of the calcium-calmodulin complex, neuronal nitric oxide synthase activation and their role in stomach distention.

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1
Department of Zoology, Michigan State University, East Lansing 48824-1115, USA.

Abstract

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.

PMID:
9025775
DOI:
10.1007/s002800050581
[Indexed for MEDLINE]
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