GLUCOCORTICOIDS DO NOT AFFECT THE INDUCTION OF A NOVEL CALCIUM-DEPENDENT NITRIC-OXIDE SYNTHASE IN RABBIT CHONDROCYTES

Incubation of rabbit articular chondrocytes with interleukin-1β caused time-dependent expression of NO synthase, determined as nitrite, after a lag period of 6h. The synthesis of nitrite was concentration-dependent and was inhibited by cycloheximide and NG-monomethyl-L-arginine, but not by dexamethasone or hydrocortisone. The synthesis of NO in the 100,000g supernatant of activated chondrocytes was inhibited by EGTA, but not by the calmodulin inhibitors W-13 or trifluoperazine. The synthesis of NO was half-maximal at approximately 20nM free Ca2+. Endotoxin also induced the expression of this NO synthase. Thus, rabbit articular chondrocytes express a novel inducible NO synthase which is Ca2+-dependent, and whose induction is not prevented by glucocorticoids. © 1992.