The L-type calcium channel blocker nimodipine mitigates cytoskeletal proteins phosphorylation in dichlorvos-induced delayed neurotoxicity in rats

Sanjeev Choudhary, Suresh Kumar Verma, Geetu Raheja, Pushpinder Kaur, Kusum Joshi, Kiran Dip Gill

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The present investigation was carried out to assess the protective efficacy of nimodipine against dichlorvos-induced organophosphate induced delayed neurotoxicity (OPIDN). Single subcutaneous dose of dichlorvos (200 mg/kg body weight) led to a consistent increase in the activity of both microtubule associated protein kinases viz. Ca2+/Calmodulin-dependent and cAMP dependent protein kinases, at all post exposure intervals (day 7, 15 and 21) as compared to that of controls. Autoradiography followed by microdensitometric studies demonstrated enhanced phosphorylation of 55 kDa and 280 kDa proteins in dichlorvos-exposed animals. These two proteins were confirmed to be tubulin and microtubule associated protein-2 (MAP-2) by western blotting. The hyperphosphorylation of these two proteins was shown to interfere with the assembly of neuronal microtubules as shown by electron microscopic studies that may eventually lead to possible disruption of neuronal cytoarchtecture resulting in axonal degeneration. Administration of nimodipine along with dichlorvos brought about a significant reduction in the activities of both the kinases as well as the extent of microtubule associated protein phosphorylation. This indicates that nimodipine, a centrally acting calcium channel blocker, may contribute to the amelioration of dichlorvos induced neurotoxicity by attenuation of calcium mediated disruption of cytoskeletal proteins and hence, calcium channel blockers like nimodipine have great future as new therapeutic agents for OPIDN.

Original languageEnglish
Pages (from-to)447-455
Number of pages9
JournalBasic and Clinical Pharmacology and Toxicology
Volume98
Issue number5
DOIs
StatePublished - May 2006
Externally publishedYes

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Dichlorvos
L-Type Calcium Channels
Nimodipine
Phosphorylation
Cytoskeletal Proteins
Calcium Channel Blockers
Rats
Microtubule-Associated Proteins
Organophosphates
Proteins
Calmodulin
Tubulin
Cyclic AMP-Dependent Protein Kinases
Autoradiography
Microtubules
Protein Kinases
Animals
Phosphotransferases
Western Blotting
Body Weight

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

The L-type calcium channel blocker nimodipine mitigates cytoskeletal proteins phosphorylation in dichlorvos-induced delayed neurotoxicity in rats. / Choudhary, Sanjeev; Verma, Suresh Kumar; Raheja, Geetu; Kaur, Pushpinder; Joshi, Kusum; Gill, Kiran Dip.

In: Basic and Clinical Pharmacology and Toxicology, Vol. 98, No. 5, 05.2006, p. 447-455.

Research output: Contribution to journalArticle

Choudhary, Sanjeev ; Verma, Suresh Kumar ; Raheja, Geetu ; Kaur, Pushpinder ; Joshi, Kusum ; Gill, Kiran Dip. / The L-type calcium channel blocker nimodipine mitigates cytoskeletal proteins phosphorylation in dichlorvos-induced delayed neurotoxicity in rats. In: Basic and Clinical Pharmacology and Toxicology. 2006 ; Vol. 98, No. 5. pp. 447-455.
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