Nitric oxide donor sodium nitroprusside induces neurotoxicity in cerebellar granular cell culture in rats by an independent mechanism from L-type or dantrolene-sensitive calcium channels.
The effects of sodium nitroprusside (SNP) in rat cerebellar granular cell culture were investigated in the present study. All doses of the SNP (10, 25, 50, 100, 250, 500 microM) were able to induce cell death compared with control values (p < 0.001 for all groups tested). Interestingly enough, a nonlinear dose-response curve was obtained for SNP-induced neurotoxicity. We also investigated the possible neuroprotective effects of nimodipine and dantrolene, alone or in combination. Both drugs failed to prevent neuronal cell death at the doses tested, either alone or in combination. Despite the fact that the most effective dose was a dantrolene concentration of 10 microM with SNP 500 microM and a concentration of 1 microM with SNP 50 microM, the differences were insignificant statistically. According to our results, SNP-induced cerebellar toxicity appears to be an independent reaction from L-type or endoplasmic reticulum calcium currents.
Gepdiremen
Akçahan
A
Department of Pharmacology, Atatürk University, Medical Faculty, Erzurum, Turkey. akcahan@atauni.edu.tr
Hacimüftüoğlu
Ahmet
A
Büyükokuroğlu
Mehmet Emin
ME
Süleyman
Halis
H
D000818:Animals; D020746:Calcium Channels, L-Type / Q000502:physiology*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects*; D003620:Dantrolene / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000633:toxicity*; D009599:Nitroprusside / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D020746:Calcium Channels, L-Type; D020030:Nitric Oxide Donors; D009599:Nitroprusside; D003620:Dantrolene