Oxyntomodulin (OXM) is a peptide isolated from porcine intestine which consists of the whole glucagon sequence with a basic octapeptide (KA,) at its C-terminal end. In this study, the effect of OXM and KAB on pentagastrin-stimulated gastric acid secretion has been studied in conscious rats and cats. In rats, OXM (25-450 pmol . kg-') as well as KA, (7.5-40 nmol ' kg-l) inhibited ~ntagast~n-stimulate gastric acid output in a dose-dependent manner; KA, was about IOO-times less potent than OXM. In cats, KA, (90 nmol . kg-') was also an inhibitor of acid secretion. We conclude that OXM, or a closely related peptide, could be a physiological modulator of gastric acid secretion, and that the C-terminal octapeptide of OXM is implicated in this effect.
Uxyntomod~ii~ Rat Cat
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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