In vitro effect of glucagon-like peptide-1 (7-36)amide, oxyntomodulin,vasoactive intestinal peptide and somatostatin on gastric acid andpepsinogen secretionA. Ben-Hamida, A. A. Houssein, W. K. Man and J. Spencer

Department of Surgery, Royal Postgraduate Medical School, London W12 0NN, UK

Introduction

The physiological effect of some incretin gastrointestinalpeptides on gastric secretion, of pepsinogen in particular, isnot entirely clear. Glucagon-like peptide-1 (GLP-1) andoxyntomodulin (OXM) are the expression products of theglucagon gene in the intestinal endocrine cells [1]. RecentlyGLP-1 was reported as possibly being the most potent inhibitorof feeding yet identified in the rat [2]. However, we foundthat neither peptide affected acid secretion in anaesthetisedrats [3]. Therefore, in the present study we used isolatedgastric glands to study the direct effect of GLP-1, OXM,somatostatin (SMS) and vasoactive intestinal peptide (VIP) onbasal and histamine-stimulated acid and pepsinogen secretion.

Materials and methods

Fasted, male Wistar rats were used for tissue donation. The gastricglands were prepared after stomach isolation [4]. The glands wereincubated with 0.1mM of the different hormones with or without 1mMhistamine or 20mM cimetidine for 30min. Acid secretion was measuredusing14C-aminopyrine accumulation as an indirect index. Pepsinogenwas assayed by measuring the rate of haemoglobin hydrolysis andexpressed as a percentage of the total pepsinogen content in the cells [5].

Results and discussion

Histamine stimulated14C-aminopyrine accumulation in adose-dependent manner (10¹7-10¹3M) and this effect wasblocked by cimetidine. Compared to the control group, at thebasal state, GLP-1 and VIP induced a significantly higher14C-aminopyrine accumulation (p< 0:030 and 0.007 respec-tively) while SMS inhibited histamine stimulation (p¼ 0:046).No test hormone affected acid secretion under cimetidineblockade ( Fig. 1).

Histamine significantly increased pepsinogen secretionfrom the basal value (p¼ 0:016). Only OXM increased basalpepsinogen secretion (p¼ 0:009). Furthermore, OXM and VIPinduced more pepsinogen secretion alone than in combinationwith histamine (p¼ 0:039 and 0.037 respectively) ( Fig. 2).

In the process of digestion the distal intestine produceshormones which can regulate gastric motor and secretoryfunctions. An increase in food intake has been demonstratedfollowing the blockade of GLP-1 receptors by exendin (9–39)and the augmentation of neuropeptide Y response withcoadministration of exendin (9–39), supporting a physiolo-gical role for GLP-1 in the central regulation of feeding [2].In contrast to our previous in vivo study, the present studyon gastric glands showed that GLP-1 increased acidsecretion. The discrepancy in the effect on acid secretionindicates that at least part of GLP-1 effect is mediated by theneural pathway.

Less attention has been devoted to the effect of GLP-1and OXM on pepsinogen secretion because acid secretion isregarded as the major determinant of gastrodudenal pathophy-siology and pepsinogen secretion plays an inconsequentialrole [6]. In this study the dissociation of the GLP-1 and OXMeffect on acid and pepsinogen secretion may indicate adifferent degree of response to various unabsorbed nutrientcontents in the gut lumen.

VIP and SMS were used as positive and negative

In¯amm. res. 46, Supplement 1(1997) S105–S106q Birkhauser Verlag, Basel, 1997

1023-3830/97/01S105-02 $ 1.50+0.20/0 Inflammation Research

Correspondence to:W. K. Man

Fig. 1. Effect of gastrointestinal hormones alone; plus histamine;and plus histamine-cimetidine on14C-aminopyrine accumulation.Mean6 SEM, n¼ 9.

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controls. Their effect on basal and stimulated acid secretionwere extensively studied. Our results showed that VIPeffectively potentiated and SMS inhibited gastric acidsecretion as was expected. Their effect on pepsinogen wasnot totally clear and needs to be reviewed with an Hþ blockerother than cimetidine which interferes with pepsinogen assay.

The most striking finding of this study is the observationthat all the tested hormones stimulated basal gastric

pepsinogen secretion. In general, the peptic activity of gastricjuice parallels acid output. The limited clinical informationobtained from tests of gastric acid secretion is not enhancedby the determination of the peptic activity of gastric juice.The role of pepsinogen and its clinical importance needs tobe investigated further. However, in this study there wasinconsistency in the response to the different peptides testedon the histamine-stimulated gastric glands acid and pepsinogensecretion. This may indicate that the insulinotropic effect ofGLP-1 and OXM is physiologically more important thantheir possible role as enterogastrone.

References

[1] Raufman JP. Gastric chief cells: receptors and signal-transductionmechanisms. Gastroenterology 1992;102:699–710.

[2] Turton MD, O’Shea D, Gunn I, Beak SA, Edwards CMB, Meeran K,et al. A role for glucagon-like-peptide-1 in the central regulation offeeding. Nature 1996;379:69–72.

[3] Ben-Hamida A, Man WK, Spencer J. The effect of some gastro-intestinal peptides on pentagastrin-stimulated acid secretion andoxyntic mucosal histamine in rats. Inflamm Res 1996;45:S46–7.

[4] Berglindh T, Obrink KJ. A method for preparing isolated glandsfrom rabbit gastric mucosa. Acta Physiol Scand 1976;96:150–9.

[5] Matsumoto K, Dickinson KEJ, Anderson W, Hirschowitz BI. Pep-sinogen secretion from perfused frog peptic glands: rapid transientsdetected with a modified pepsin assay. Life Sci 1988;42:1237–44.

[6] Joffe SN, Roberts NB, Taylor WH, Baron JH. Exogenous andendogenous acid and pepsins in the pathogenesis of duodenal ulcersin the rat. Dig Dis Sci 1980;25:837–41.

S106 Inflamm. res.,Supplement 1(1997)

Fig. 2. Effect of gastrointestinal hormones alone and plus histamine onpepsinogen secretion. Mean6 SEM, n¼ 9.

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