Chloride-dependent amino acid transport in the small intestine: occurrence and significance.

The unidirectional influx of amino acids, D-glucose and ions across the brush-border membrane of the small intestine of different species has been measured in vitro with emphasis on characterization of topographic and species differences and on chloride dependence. The regional differences in transport along the small intestine are outlined and shown to be caused by variation in transport capacity, while the apparent affinity constants are unchanged. Rabbit small intestine is unique by exhibiting maximal rates of transport in the distal ileum and a very steep decline in the oral direction from where tissues are normally harvested for preparation of brush-border membrane vesicles. Transport in the guinea pig and rat is much more constant throughout the small intestine. Since the capacity of nutrient carriers is regulated by their substrates it is possible that bacterial breakdown of peptides and proteins in rabbit distal ileum increases the concentration of amino acids leading to an upregulation of the carriers. Chloride dependence is a characteristics of the carrier rather than the transported amino acid, and is used to improve the classification of amino acid carriers in rabbit small intestine. In this species the imino acid carrier, the beta-amino acid carrier, and the beta-alanine carrier, which should be renamed the B0,+ carrier, are chloride-dependent. The steady-state mucosal uptake of classical substrates for these carriers in biopsies from the human duodenum is also chloride-dependent. The carrier of beta-amino acids emerges as ubiquitous and chloride-dependent, and evidence of cotransport with both sodium and chloride is reviewed. A sodium:chloride:2-methyl-aminoisobutyric acid coupling stoichiometry of approx. 2:1:1 is suggested by ion activation studies. Direct measurements of coupled ion fluxes in rabbit distal ileum confirm that sodium, chloride and 2-methyl-aminoisobutyric acid are cotransported on the imino acid carrier with an identical influx stoichiometry. Control experiments and reference to the literature on the electrophysiology of the small intestine exclude alterations of the membrane potential as a feasible explanation of the chloride dependence. Thus, it is concluded that chloride is cotransported with both sodium and 2-methyl-aminoisobutyric acid across the brush-border membrane of rabbit distal ileum.