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RECEPTORS AND SIGNAL TRANSDUCTION

Effect of pH on L- and D-methionine uptake across the apical membrane of Caco-2 cells

¹Departament de Fisiologia, Facultat de Farmàcia, Universitat de Barcelona, Barcelona, Spain; and ²Adisseo France S.A.S., Antony, France

Submitted 20 September 2008 ; accepted in final form 6 January 2009

The transport systems involved in intestinal methionine (Met) absorption are described as Na⁺-dependent and Na⁺-independent mechanisms. However, since recent studies have suggested the importance of the H⁺ gradient as a driving force for intestinal nutrient absorption, the aim of the present work was to test whether Met transport across the apical membrane of Caco-2 cells is affected by extracellular pH. The results show that L- and D-Met uptake was increased by lowering extracellular pH from 7.4 to 5.5, in both the presence and absence of Na⁺. Cis-inhibition experiments revealed that inhibition of L-Met transport by 2-aminobicyclo[2,2,1]heptane-2-carboxylic acid (BCH) or L-lysine (L-Lys) was higher at a pH of 5.5. Moreover, the BCH-insensitive component was not affected by pH, whereas the L-Lys-insensitive component was increased by lowering extracellular pH, thus suggesting the participation of system L. The contribution of another mechanism, sensitive to both BCH and L-Lys, was also considered. The inhibition obtained with taurine (Tau) was also higher at a pH of 5.5, thus suggesting the involvement of system B^0,+ on pH-stimulated component. As for D-Met uptake, the results showed higher inhibition with L-Lys and Tau at a pH of 5.5 and no effect on the L-Lys- or Tau-insensitive component. In conclusion, Met transport across the apical membrane of Caco-2 cells is increased by low extracellular pH as the result of the stimulation of two transport systems functionally identified with systems L and B^0,+ for L-Met and with system B^0,+ for D-Met.

intestine; amino acid transport; H⁺ gradient

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