Cancer Chemotherapy and Pharmacology

, Volume 39, Issue 4, pp 341–348

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

  • R. K. Jarve
  • S. K. Aggarwal
ORIGINAL ARTICLE

DOI: 10.1007/s002800050581

Cite this article as:
Jarve, R. & Aggarwal, S. Cancer Chemother Pharmacol (1997) 39: 341. doi:10.1007/s002800050581

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, immunohistochemicaly the levels of L-citrulline and the Ca2+-calmodulin complex were decreased after only 3 days. An in vitro experiment using an analog of calmodulin, MeroCalmodulin-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.

Key words Neuronal nitric oxide synthase Calcium-calmodulin complex Cisplatin Stomach distention Emesis 

Copyright information

© Springer-Verlag Berlin Heidelberg 1996

Authors and Affiliations

  • R. K. Jarve
    • 1
  • S. K. Aggarwal
    • 1
  1. 1.Department of Zoology, Michigan State University, East Lansing, MI 48824-1115, USAUS

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