Gastric Secretory Response to Intravenous Amino Acids in Eviscerated Dogs

Mariano, Elpidio C.

doi:10.1001/archsurg.1978.01370170073014

Cited by 8 publications

(4 citation statements)

References 25 publications

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“…Since serum gastrin does not increase with either intraduodenal or intravenous amino acid infusion (1)(2)(3), it has been postulated that the intestinal phase of gastric acid secretion may be due at least in part to the direct or indirect effect of circulating amino acids on or near the parietal cell (2,6). After removal of the gastric antrum, small bowel, colon, and pancreas, Marino and Landor (7) observed that an intravenous infusion of a mixture of L-amino acids stimulated gastric acid secretion in the vagotomized dog. This observation further supports the hypothesis that amino acids may have a direct effect on or near the canine parietal cell.…”

Section: Introductionmentioning

confidence: 99%

Intravenous infusion of L-isomers of phenylalanine and tryptophan stimulate gastric acid secretion at physiologic plasma concentrations in normal subjects and after parietal cell vagotomy.

McArthur¹,

Isenberg²,

Hogan³

et al. 1983

J. Clin. Invest.

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A B S T R A C T To determine whether intravenous infusion of individual amino acids stimulated gastric acid secretion in man, graded doses of phenylalanine, tryptophan, glycine, alanine, histidine, and NaCl control were infused on separate days in nine healthy subjects. Intravenous infusion of phenylalanine and tryptophan significantly stimulated gastric acid secretion to 50 and 52%, respectively, of the acid secretory response to intragastric peptone. Intravenous alanine and histidine were without effect, whereas glycine produced a slight response. Serum gastrin concentrations did not significantly change during intravenous amino acid infusion, except in response to 0.1 M phenylalanine. However, the increase in serum gastrin occurred 2 h after acid secretion had significantly increased in response to the 0.025 M phenylalanine infusion. Plasma amino acid concentrations were measured during intravenous amino acid infusion and in response to a steak meal in five of the subjects. At a time when acid secretion was significantly increased during intravenous infusion of phenylalanine and tryptophan, plasma amino acids were similar to, or less than, that observed after the steak meal, suggesting that circulating levels of these three amino acids have a physiologic effect on gastric secretion in man. Intravenous infusion of a combination of graded doses of phenylalanine plus a continuous infusion of 0.01 M tryptophan shifted the dose-response curve to the left and resulted in a significantly greater response than to either amino acid alone. In five subjects with parietal cell vagotomy, intravenous phenylalanine and tryptophan stimulated acid secretion, whereas histidine was without effect, similar to normal subjects. These studies indicate that intravenous infusion of small amounts of phenylalanine (0.025 M, 3.1 mmol/ h) and tryptophan (0.01 M, 1.25 mmol/h) stimulated gastric acid secretion at plasma concentrations similar to those observed after a steak meal, suggesting a physiologic role for circulating levels of these amino acids on gastric acid secretion. Because acid secretion increased at a time when serum gastrin was unchanged and since there was no correlation between changes in serum gastrin and acid secretion, the responses to phenylalanine and tryptophan are probably mediated by a nongastrin-related mechanism(s). Since both phenylalanine and tryptophan stimulated secretion in vagotomized subjects, the response is vagally independent. These observations suggest that circulating levels of these two amino acids have either a direct or indirect effect on or near the human parietal cell.

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Section: Introductionmentioning

confidence: 99%

Intravenous infusion of L-isomers of phenylalanine and tryptophan stimulate gastric acid secretion at physiologic plasma concentrations in normal subjects and after parietal cell vagotomy.

McArthur¹,

Isenberg²,

Hogan³

et al. 1983

J. Clin. Invest.

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“…These data indi cate that amino acids stimulate gastric acid secretion at least independent of vagal mech anisms although data obtained from Heiden hain pouch experiments do not exclude the possibility of intramural neurons mediating the amino acid effect. Moreover, it has been noted that intravenous infusion of amino acids stimulated gastric acid secretion with out increasing serum gastrin [2,5,6,9], The influence of gastrointestinal hormones other than gastrin is also unlikely since removal of the gastric antrum, small intestine, colon, and pancreas did not abolish the acid-stimu lating effect of intravenous amino acids in vagotomized dogs [8], In vivo, L-phenylalanine and L-tryptophan were among the most potent acid-stimulating amino acids increas ing gastric acid secretion to approximately 50% of the maximal response to a peptone meal; L-arginine, although being less effec tive, significantly stimulated gastric acid se cretion [5,9]. Effective plasma levels of in travenously infused L-phenylalanine or Ltryptophan ranged between approximately 8 X 10_5A/ to 2 X 10~4 M [5] which corre sponds to the intermediate range of concen trations which we tested in vitro.…”

Section: Discussionmentioning

confidence: 99%

“…The effect of intragastric or intraduodenal amino acids has been attributed either to the release of an acid-stimulating gastrointestinal hormone, in particular gas trin [3], or to a direct effect on the parietal cells [1,2]. More unequivocally, the effect of intravenous amino acids has been speculated to be due to a direct action on the parietal cells [2,6,8,9]. Yet, thus far no direct evi dence for this hypothesis has been obtained.…”

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confidence: 99%

Effect of Amino Acids on H<sup>+</sup> Production by Isolated Rat Parietal Cells

Schmidtler¹,

Schepp²,

Schusdziarra³

et al. 1989

Digestion

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We investigated the hypothesis of a direct effect of amino acids on gastric parietal cells. [¹⁴C]aminopyrine uptake into isolated enriched rat parietal cells served as a quantitative index of H⁺ production. Cells were incubated in media containing 1 mM Ca²⁺ in the absence or presence of the phosphodiesterase inhibitor 3-isobutyl-l-methylxanthine (IBMX), or 3 mM Ca²⁺ without IBMX. Under these different conditions, L-arginine, L-phenylalanine and L-tryptophan (10^-6M to 3 × 10^-2M) failed to alter basal [¹⁴C]aminopyrine uptake as well as the response to submaximal stimulation by histamine, forskolin, N⁶O²-dibutyryladenosine-3´,5´-(cyclic)-phosphate (db cAMP) or carbachol. Pentagastrin failed to elicit an appreciable response in the presence and absence of 10^-3 M of all three amino acids studied. It is concluded that in vivo the potent stimulation of gastric acid secretion by L-arginine, L-phenylalanine and L-tryptophan is mediated by other than direct mechanisms.

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“…It is well established that amino acids are capable of directly stimulating the parietal cell [121]. Systemic intravenous administration of amino acids in dogs and humans has been shown to stimulate acid secretion from the innervated and denervated stomach to the same extent as instillation of amino acids in the duodenum or jejunum [101,107,109,115,117,[122][123][124], and to produce no changes in serum gastrin concentration [109,115,117,122]. Administration of amino acids by the portal venous route in dogs has been observed to have little or no gastric stimulatory effect, in contrast to systemic administration [109,123].…”

Section: Physiologic Evidence For An Intestinal Phase Hormonementioning

confidence: 99%

The intestinal phase hormone

et al. 1979

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The existence of a stimulatory intestinal phase of gastric acid secretion has been suspected, but largely ignored, for many years. Recently, however, it has become clear that the intestinal phase plays an important role in acid production during digestion. The intestinal phase is of additional interest in relation to the profound gastric acid hypersecretion associated with portacaval shunt (PCS). Substantial evidence indicates that PCS-related gastric hypersecretion is due to unmasking of the intestinal phase by hepatic bypass of a humoral stimulant in portal blood that is normally degraded to a considerable extent by the liver. Studies in our laboratory during the past 12 years have provided strong physiologic evidence for humoral mediation of both the intestinal phase of gastric secretion and of PCS-related hypersecretion by a hormone that arises in the small intestine, particularly in the jejunum. Furthermore, our studies have demonstrated that this intestinal phase hormone (IPH) exists in humans as well as in dogs, rats, and pigs. Additionally, recent work by a number of investigators, as well as by our group, has provided convincing evidence that IPH is different from any of the known gastric stimulatory hormones. With these physiologic observations as a background, we have used a classical method for extracting acidic peptides to prepare a hog intestinal mucosa extract (HIME) that has all of the known physiologic properties of an IPH. Specifically, HIME contains a potent stimulant of gastric acid secretion that acts according to a linear dose-response relationship; that is not gastrin in any of its immunoassayable forms; that significantly augments the maximal acid secretory responses to pentagastrin, gastrin, CCK, and histamine; and that is substantially degraded by the liver, in contrast to gastrin and CCK. Efforts at isolating the gastric stimulatory substance in HIME suggest that it is a peptide of low molecular weight. Work directed at isolating IPH in pure form and identifying it is in progress.

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Gastric Secretory Response to Intravenous Amino Acids in Eviscerated Dogs

Cited by 8 publications

References 25 publications

Intravenous infusion of L-isomers of phenylalanine and tryptophan stimulate gastric acid secretion at physiologic plasma concentrations in normal subjects and after parietal cell vagotomy.

Intravenous infusion of L-isomers of phenylalanine and tryptophan stimulate gastric acid secretion at physiologic plasma concentrations in normal subjects and after parietal cell vagotomy.

Effect of Amino Acids on H<sup>+</sup> Production by Isolated Rat Parietal Cells

The intestinal phase hormone

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