ROLES OF PURINE NUCLEOTIDES AND ADENOSINE IN ENHANCING NOS-II GENE-EXPRESSION IN INTERLEUKIN-1-BETA-STIMULATED RAT VASCULAR SMOOTH-MUSCLE CELLS

The production of nitric oxide (NO) by vascular smooth muscle cells (V SMC) is stimulated by interleukin-1 beta (IL-1 beta). This is enhanced in a dose-dependent dent manner by ADP, although it alone failed to i nduce nitrite accumulation. Purine nucleotides and their nonhydrolizab le analogues as well as adenosine also exhibit variable enhancing effe cts. This enhanced nitrite formation was due to induction of the NO sy nthase (NOS II) gene as judged by Northern hybridization using an NOS II specific probe and by Ca2+ independency of the NOS activity. 8-(p-S ulfophenyl)-theophylline, a blocker of adenosine receptors, suppressed the enhanced NO production by adenosine and ADP to the level of that with IL-1 beta alone. These data indicate that activation of the adeno sine receptor on VSMC may enhance production of NOS II by modulating a signal transducing pathway of IL-1 beta. Although cAMP is a candidate as the second messenger, it was not significantly elevated by either ADP or adenosine treatment in IL-1 beta-stimulated cells. This mechani sm might be stimulated under conditions with release of various purine and their derivatives.