Summary.The ordinary aliphatic, neutral amino acids and phenylalanine have been examined for cis-inhibition of influx of alanine (J~22) and lysine (Jl ys) and trans-stimulation of Y~ across the brush border membrane of rat small intestines: and their effects on the unidirectional mucosa-to-serosa flux (J~2)across the short circuited intestine have been studied. The effects of alanine, s-amino-n-butyric acid, leucine, and methionine on the steady-state epithelial uptake of lysine [Lys]c have also been measured. In addition the trans-effects of alanine and leucine have been examined for sodium-dependence, and alanine was tested as trans-stimulator of influx of galactose across the brush border membrane (Jgma~).All the neutral amino acids were found to be competitive cis-inhibitors of J~ s, and all, except isoleucine, were trans-stimulators of j~;v~. The magnitude of the trans-effect was unrelated to the efficiency of the amino acid as cis-inhibitor. As illustrated by alanine, the trans-effects are probably completely sodium-dependent. Alanine was also effective as trans-stimulator of Ygm~. With respect to effects on [Lys]c and J~ the neutral amino acids fall into two groups: One which reduces [Lys]c and stimulates J~], and one which increases [Lys]c and relatively inhibits j~ys. These effects are not correlated with the affinities of the neutral amino acids for the two carriers involved.It is proposed that the trans-effects on J~c ~ are induced by an electrogenic, sodium-coupled efflux of the neutral amino acid across the brush border membrane, that the stimulation of jlys is brought about by a selective stimulation (of unknown nature) of efflux of lysine across the basolateral membrane (J~Y~), assisted by competitive inhibition of lysine efflux across the brush border membrane (J~), and that the amino acids which do not stimulate J~Y~ increase [Lys]c by competitively inhibiting f ys and J~.The inhibitory effect of the neutral amino acids on j~s support the view that the carrier of basic amino acids serves as a second carrier of these amino acids.
Key words:Intestinal transport, small intestine, lysine, neutral amino acids.The interactions between neutral (~-amino-monocarboxylic acids) and basic (diamino acids) during passage of the membranes of intestinal epithelia have been studied by sacs of everted intestine [7][8][9]20], by rings of everted intestine [26,28,29], by isolated mucosa [16], and by isolated intestinal cells [22 25], by measurements of unidirectional transepithelial fluxes, and by measuring influx across the brush border membrane [16,15]. In these different inhibitory and stimulating effects of neutral amino acids on the transport of basic amino acids have been observed. The results obtained with different techniques appear contradictory, and although different investigators get the same results when they use identical techniques [12,28], the conclusions drawn differ markedly [16,27].This diversity of opinions invites further study. In addition, further insight into the mechanisms of epithelial tran...