AJP - Lung Cellular and Molecular Physiology, Vol 265, Issue 5 456-L461, Copyright © 1993 by American Physiological Society

ARTICLES

cAMP regulates soluble guanylate cyclase beta 1-subunit gene expression in RFL-6 rat fetal lung fibroblasts

A. Shimouchi, S. P. Janssens, D. B. Bloch, W. M. Zapol and K. D. Bloch
Department of Anesthesia, Harvard Medical School, Boston, Massachusetts.

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.

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