Stimulation of Three Distinct Guanylate Cyclases Induces Mucosal Surface Alkalinisation in Rat Small Intestine in vitro

• Published in: Comparative biochemistry and physiology. A, Comparative physiology Vol. 118; no. 2; pp. 291 - 295
• Main Authors: Fawcus, Karen, Gorton, Victoria J, Lucas, Michael L, McEwan, Gordon T.A
• Format: Journal Article
• Language: English
• Published: United States Elsevier B.V 01.10.1997
• Subjects: acid microclimate; Alkalies; Animals; atrial natriuretic factor; Atrial Natriuretic Factor - pharmacology; Bacterial Toxins - pharmacology; cyclic GMP; E. coli STa enterotoxin; Enterotoxins - pharmacology; Enzyme Inhibitors - pharmacology; Escherichia coli Proteins; Female; guanylate cyclase; Guanylate Cyclase - drug effects; Hydrogen-Ion Concentration; In Vitro Techniques; Intestinal Mucosa - drug effects; Intestinal Mucosa - enzymology; Intestine, Small - drug effects; Intestine, Small - enzymology; Methylene Blue - pharmacology; mucosal surface pH; nitric oxide; Nitroprusside - pharmacology; Rats; Rats, Sprague-Dawley; Small intestine; sodium nitroprusside; Sodium-Hydrogen Exchangers - metabolism; Stimulation, Chemical; E. coli STa enterotoxin; nitric oxide; sodium nitroprusside; guanylate cyclase; cyclic GMP; atrial natriuretic factor; mucosal surface pH; Small intestine; acid microclimate
• ISSN: 0300-9629; 1096-4940
• DOI: 10.1016/S0300-9629(96)00307-6

The absorptive surface of the small intestine is isolated from bulk pH changes in the luminal contents by a zone of maintained low pH, the acid microclimate. The present study set out to compare the effects of stimulation of each of the three guanylate cyclases (GCs) expressed in the intestinal mucosa on the pH microclimate of rat jejunum in vitro. The tissue was exposed to specific ligands for each of the GCs and mucosal surface pH determinations were made by a miniaturised glass pH electrode. The ligands used were E. coli STa enterotoxin, atrial natriuretic peptide (ANP) and nitric oxide (NO, via the donor sodium nitroprusside (SNP)). Challenge from all three agonists resulted in significant alkalinisation of the jejunal mucosa. The actions of SNP were blocked by the soluble GC inhibitor, methylene blue (MB) whereas those of STa were unaffected by MB. The data are consistent with previous observations that cGMP-induced inhibition of brush border Na +/H + exchange results in elevation of mucosal surface pH. We conclude that all three of the identified GC pathways in the intestinal mucosa are capable of contributing to the control of mucosal acidification in the upper small intestine.