Effects of Monovalent Cations

H, K, Rb, and Li inhibit Na-dependent alanine influx across the brush border of rabbit ileum. Kinetic analysis indicates that H and K behave as competitive inhibitors of influx so that increasing the concentration of H or K in the mucosal solution is kinetically indistinguishable from decreasing the Na concentration. In addition the coupling between alanine and Na influxes is markedly reduced at pH 2.5. With the exception of H and Li, none of these monovalent cations significantly affects carrier-mediated alanine influx in the absence of Na indicating that their inhibitory effects are largely restricted to the Na-dependent fraction of influx. Increasing H concentration from 0.03 to 3 mM does not affect influx in the absence of Na but markedly inhibits influx in the presence of Na. Li significantly enhances alanine influx in the absence of Na. Ag, U0 2 , and La also inhibit the Na-dependent fraction of alanine influx. These findings suggest that anionic groups having a pKa of approximately 4 are involved in the interaction between Na and the alanine-carrier complex; present evidence implicates carboxylate groups however, phosphoryl residues cannot be ruled out. The previously proposed kinetic model for the Na-alanine interaction has been extended to accommodate these effects of H and other monovalent cations. The mechanistic and physiological implications of these findings are discussed. The interaction between Na and the influx of alanine across the brush border of rabbit small intestine has been examined in considerable detail and a model consistent with the kinetics of this interaction has been presented (1). According to this model, alanine combines first with a component of the brush border to form a binary complex. This binary complex can either cross the membrane or it can combine with Na to form a ternary complex that then crosses the membrane. Kinetic data indicate that the dissociation constant of the binary complex is much greater than that of the ternary complex. Thus, Na enhances influx because it promotes the formation of a more stable complex; the greater the stability of the ternary complex compared to that of the