PRODUCTION AND LOCALIZATION OF CGMP AND PGE(2) IN NITROPRUSSIDE-STIMULATED RAT COLONIC ION-TRANSPORT

Nitrovasodilators, such as sodium nitroprusside (SNP), release nitric oxide (NO) and stimulate intestinal electrolyte transport. However, th e second messengers involved in this process are unknown. NO stimulate s soluble guanylate cyclase activity in other tissues, but stimulation of this enzyme has not previously been described for intestine. We re port a 20-fold increase in guanosine 3',5'-cyclic monophosphate (cGMP) production by radioimmunoassay in colonic mucosal strips stimulated w ith SNP. SNP also caused a significant increase in prostaglandin (PG) E(2) release but did not stimulate release of the prostanoids thrombox ane B-2 or B-keto-PGF(1 alpha). Stimulation of isolated colonic crypts and the remaining subepithelial mucosa demonstrated that the latter w as the major source of the increases in cGMP and PGE(2). Immunostainin g of colonic mucosa revealed minimal basal cGMP immunoreactivity but l arge increases in abundance, localizing to the subepithelium, after SN P treatment. Under basal conditions, there was diffuse immunostaining for constitutive NO synthase in both the epithelial and subepithelial compartments, which was corroborated with NADPH diaphorase staining. I n conclusion, SNP as an NO donor stimulates production of cGMP and PGE (2) from the subepithelium. NO may be an important mediator of colonic secretion and other processes predominantly via its direct effects on cells of the lamina propria.