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Editor,—Wapnir et al (Gut1997;40:602–7) reported interesting observations on the effect of l-arginine in low concentrations on intestinal water and sodium absorption from rat jejunum, in experiments which they carried out to determine the possible proabsorptive effect of this amino acid if included in oral rehydration solutions. Their results, showing that perfusion of very low concentrations of arginine stimulated sodium and water absorption, but higher concentrations had the reverse effect, recalled to mind observations we made many years ago in the course of a systematic study of the effect of amino acids on sodium and water absorption in human jejunum.1
In double lumen intestinal perfusion studies we found that, in contrast with the neutral amino acids glycine and alanine, perfusion solutions containing arginine did not stimulate sodium and water absorption, and at higher concentrations were associated with fluid secretion. We have vivid personal recollection of the choleraic diarrhoea that could be the result. In contrast to the findings in the rat jejunum reported by Wapnir et al, no stimulation of fluid absorption occurred in human jejunum at concentrations of arginine as low as 10 mM and 20 mM. The anomalous effect of arginine on sodium and water absorption puzzled us at the time, and it is interesting to speculate that it may be due to nitric oxide induced vasodilatation.
Editor,—Hellier and Holdsworth pertinently refer to their pioneering 1973 paper1-1 on the effects of certain amino acids and dipeptides on intestinal absorption in humans.l-arginine was studied as a paradigm of a basic amino acid. The secretory response it elicited stood in sharp contrast to the proabsorptive action of glycine, l-alanine and two dipeptides. Furthermore, at 20 mM it produced frank diarrhoeic effects and discomfort. When 10 mM l-arginine was added to isotonic saline, both sodium and water transport were essentially in equilibrium (fig 3 in reference 1). In our experiments with rats, at that concentration, l-arginine had no stimulatory effect, and was indistinguishable from a baseline with no l-arginine. However, a significant difference in the design of the experiments was the presence of a relatively high concentration of glucose (111 mM) in the oral rehydration solutions (ORS) we tested. Other investigators have shown that in the absence of glucose, 20 mM l-arginine abolished net water and sodium absorption.1-2 In separate experiments 10 mM glucose neutralised the secretory effect of 40 mMl-arginine.1-3 Sodium–glucose co-transport is a key factor that will produce a notable shift in the response of the small intestine to secretory agents, as clearly shown in animal and human studies.1-2 1-3 Hence, the studies cannot be compared directly. Whether the stimulatory effects obtained in rats with low concentrations of l-arginine (1–2 mM) added to ORS can also be observed in humans has yet to be determined.
l-arginine is not the only amino acid known to have a negative effect on fluid and electrolyte absorption.l-tryptophan also has a secretory action1-4 and there is evidence that activation of the serotonin pathway is involved.1-5 The apparent concentration dependent vasodilator and vasoconstrictor properties of nitric oxide (NO), presumably generated by induction of NO synthase froml-arginine in the small intestinal mucosa, deserve further examination.