Inhibition of rat brain nitric oxide synthase activity by cyclosporin-A.
Cyclosporin-A, a potent immunosuppressive agent is known to induce cellular toxic side effects by way of altering calcium homeostasis, including calcium/calmodulin mediated events. We studied the in vitro and in vivo effects of cyclosporin-A on rat brain nitric oxide synthase activity (the enzyme that mediates the conversion of L-arginine to citrulline and NO). CsA in concentrations of 22-4400 nM inhibited rat brain NOS activity in vitro and in 10 or 25 mg/kg wt/4 weeks of CsA treated rat brains in vivo. We report here that CsA by way of interfering with rat brain Ca2+/CaM mediated events may inhibit its NOS activity which ultimately may result in neurotoxicity.
Rao
M R
MR
Department of Zoology, S.V. University, Tirupati, India.
Kanji
V K
VK
Salahudeen
M K
MK
Wang
C
C
Sekhar
V
V
D000818:Animals; D001921:Brain / Q000201:enzymology*; D016572:Cyclosporine / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D019001:Nitric Oxide Synthase