Stimulation of three distinct guanylate cyclases induces mucosal surface alkalinisation in rat small intestine in vitro

K Fawcus, V J Gorton, M L Lucas, G T McEwan

Research output: Contribution to journalArticle

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Abstract

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.
Original languageEnglish
Pages (from-to)291-5
Number of pages5
JournalComparative Biochemistry and Physiology. A, Physiology
Volume118
Issue number2
Publication statusPublished - Oct 1997

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Guanylate Cyclase
Small Intestine
Microclimate
Methylene Blue
Nitroprusside
Intestinal Mucosa
Ligands
Atrial Natriuretic Factor
Jejunum
Microvilli
Glass
In Vitro Techniques
Nitric Oxide
Electrodes
Mucous Membrane
Escherichia coli
Acids

Keywords

  • Alkalies
  • Animals
  • Atrial Natriuretic Factor
  • Bacterial Toxins
  • Enterotoxins
  • Enzyme Inhibitors
  • Escherichia coli Proteins
  • Female
  • Guanylate Cyclase
  • Hydrogen-Ion Concentration
  • Intestinal Mucosa
  • Intestine, Small
  • Methylene Blue
  • Nitroprusside
  • Rats
  • Rats, Sprague-Dawley
  • Sodium-Hydrogen Antiporter
  • Stimulation, Chemical

Cite this

Stimulation of three distinct guanylate cyclases induces mucosal surface alkalinisation in rat small intestine in vitro. / Fawcus, K; Gorton, V J; Lucas, M L; McEwan, G T.

In: Comparative Biochemistry and Physiology. A, Physiology, Vol. 118, No. 2, 10.1997, p. 291-5.

Research output: Contribution to journalArticle

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AB - 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.

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