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 guanosine 3',5'-cyclic monophosphate (cGMP). To investigate the regulation of this important EDRF/NO receptor, we studied soluble guanylate cyclase gene expression in a rat fetal lung fibroblast cell line (RFL-6). 3-Isobutyl-1-methylxanthine, forskolin, and dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP), agents which increase intracellular cAMP, decreased the concentration of mRNA encoding the beta 1-subunit of soluble guanylate cyclase in RFL-6 cells. To investigate whether a decrease in beta 1-subunit mRNA concentration was reflected in diminished capacity to produce cGMP, forskolin-treated RFL-6 cells were exposed to the NO-donor compound sodium nitroprusside. Exposure to forskolin reversibly reduced the ability of RFL-6 cells to increase cGMP in response to NO. These observations suggest that cAMP can modulate the cellular response to EDRF/NO by decreasing the expression of one of the subunits of soluble guanylate cyclase.
Shimouchi
A
A
Department of Anesthesia, Harvard Medical School, Boston, Massachusetts.
Janssens
S P
SP
Bloch
D B
DB
Zapol
W M
WM
Bloch
K D
KD
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology*; D006162:Guanylate Cyclase / Q000096:biosynthesis*; D007700:Kinetics; D008168:Lung; D046911:Macromolecular Substances; D009599:Nitroprusside / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000302:isolation & purification / Q000378:metabolism; D051381:Rats
D046911:Macromolecular Substances; D012333:RNA, Messenger; D009599:Nitroprusside; D005576:Colforsin; D003994:Bucladesine; D000242:Cyclic AMP; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D015056:1-Methyl-3-isobutylxanthine