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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.