CAMP REGULATES SOLUBLE GUANYLATE-CYCLASE BETA-1-SUBUNIT GENE-EXPRESSION IN RFL-6 RAT FETAL LUNG FIBROBLASTS

Endothelium-derived relaxing factor (EDRF)/nitric oxide (NO) activates soluble guanylate cyclase, thereby stimulating the synthesis of guano sine 3',5'-cyclic monophosphate (cGMP). To investigate the regulation of this important EDRF/NO receptor, we studied soluble guanylate cycla se gene expression in a rat fetal lung fibroblast cell line (RFL-6). 3 -Isobutyl-1-methylxanthine, forskolin, and dibutyryl adenosine 3',5'-c yclic monophosphate (cAMP), agents which increase intracellular cAMP, decreased the concentration of mRNA encoding the beta1-subunit of solu ble guanylate cyclase in RFL-6 cells. To investigate whether a decreas e in beta1-subunit mRNA concentration was reflected in diminished capa city to produce cGMP, forskolin-treated RFL-6 cells were exposed to th e NO-donor compound sodium nitroprusside. Exposure to forskolin revers ibly reduced the ability of RFL-6 cells to increase cGMP in response t o NO. These observations suggest that cAMP can modulate the cellular r esponse to EDRF/NO by decreasing the expression of one of the subunits of soluble guanylate cyclase.