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Am J Physiol Gastrointest Liver Physiol 264: G816-G823, 1993;
0193-1857/93 $5.00
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AJP - Gastrointestinal and Liver Physiology, Vol 264, Issue 5 816-G823, Copyright © 1993 by American Physiological Society

ARTICLES

Inhibition of gastric acid secretion by oxyntomodulin and its 19-37 fragment in the conscious rat

C. Jarrousse, C. Carles-Bonnet, H. Niel, R. Sabatier, M. P. Audousset-Puech, P. Blache, A. Kervran, J. Martinez and D. Bataille
Centre National de la Recherche Scientifique, Institut National de la Sante et de la Recherche Medicale de Pharmacologie-Endocrinologie, Montpellier, France.

Oxyntomodulin (Oxm) is a hormone, released from the intestine during digestion. Its target tissue is the gastric mucosa, where it inhibits acid secretion. It contains the 29-amino acid glucagon moiety, extended at its COOH-terminal end by an octapeptide. The glucagon moiety contains a basic doublet (Arg17-Arg18). Our working hypothesis was that the mode of action of Oxm may imply a processing of the molecule at the Arg-Arg doublet, releasing Oxm-(19-37). We compared the effect of Oxm with that of Oxm-(19-37) on gastric acid secretion in the conscious rat provided with a chronic gastric fistula. The acid secretion was plateau stimulated by a perfusion of either pentagastrin or histamine. Whereas Oxm or Oxm-(19-37) had no effect on basal acid secretion, both peptides inhibited pentagastrin (0.5 micrograms.kg-1.h-1)- and histamine (0.4 mg.kg-1.h-1)-stimulated acid secretion in a dose-dependent manner. When the metabolic clearance rate for each peptide was taken into account, the 19-37 fragment was as potent as the whole Oxm, regardless of the type of stimulant. When the dose of pentagastrin was increased from 0.175 to 1.1 micrograms.kg-1.h-1, the extent of inhibition induced by Oxm (40 pmol/kg) also increased. In contrast, when the dose of histamine was increased from 0.25 to 1.2 mg.kg-1.h-1, the extent of inhibition induced by Oxm (40 pmol/kg) decreased. Oxm-(19-37) (70-140 pmol/kg) displayed the same behavior as the whole molecule under both types of stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)


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