TY - JOUR
T1 - Relationship between structure and permeability of tryptophan derivatives across human intestinal epithelial (Caco-2) cells
AU - Urakami, Machiko
AU - Ano, Rieko
AU - Kimura, Yukitaka
AU - Shima, Motohiro
AU - Matsuno, Ryuichi
AU - Ueno, Tamio
AU - Akamatsu, Miki
N1 - Funding Information:
We are thankful to Professor Everett Bandman of University of California at Davis for careful reviewing this manuscript. This study was supported in part by the Hayashi Memorial Foundation for Female Natural Scientists.
PY - 2003
Y1 - 2003
N2 - L-Trp and its derivatives were used as model compounds to clarify structural factors which influence the intestinal epithelial permeation and metabolism of amino-acid derivatives. Permeability of model compounds through Caco-2 cells was used as an in vitro absorption model for human intestinal epithelial cells. The influence of compound concentration, the effects of various transporter substrates on permeability coefficients, and pH dependency of permeability coefficients were investigated. The transcellular permeability of Trp and Trp-NH2 in the direction from the apical side to the basolateral side, in which nutrients and drugs were ordinarily absorbed, declined with increasing concentration and saturated at more than 1 and 0.4 mM, respectively. The permeability coefficients for N-terminal protected Trp derivatives and Ac-Trp-NH2 showed similar and constant values in both from the apical-to-basolateral and basolateral-to-apical directions. In addition, significant inhibition of the apical-to-basolateral permeation of Trp by Leu and Phe was observed. The permeability coefficient ratio at pH 6.3 to that at pH 7.3 was explained by the ratio of the ionic form to the neutral form of the compounds. Based upon these results and the partition coefficients in the 1-octanol/water system, possible absorption mechanism of Trp and its derivatives across Caco-2 cells was proposed.
AB - L-Trp and its derivatives were used as model compounds to clarify structural factors which influence the intestinal epithelial permeation and metabolism of amino-acid derivatives. Permeability of model compounds through Caco-2 cells was used as an in vitro absorption model for human intestinal epithelial cells. The influence of compound concentration, the effects of various transporter substrates on permeability coefficients, and pH dependency of permeability coefficients were investigated. The transcellular permeability of Trp and Trp-NH2 in the direction from the apical side to the basolateral side, in which nutrients and drugs were ordinarily absorbed, declined with increasing concentration and saturated at more than 1 and 0.4 mM, respectively. The permeability coefficients for N-terminal protected Trp derivatives and Ac-Trp-NH2 showed similar and constant values in both from the apical-to-basolateral and basolateral-to-apical directions. In addition, significant inhibition of the apical-to-basolateral permeation of Trp by Leu and Phe was observed. The permeability coefficient ratio at pH 6.3 to that at pH 7.3 was explained by the ratio of the ionic form to the neutral form of the compounds. Based upon these results and the partition coefficients in the 1-octanol/water system, possible absorption mechanism of Trp and its derivatives across Caco-2 cells was proposed.
KW - Caco-2
KW - Structure-Permeability Relationships
KW - Tryptophan Derivatives
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U2 - 10.1515/znc-2003-1-223
DO - 10.1515/znc-2003-1-223
M3 - Article
C2 - 12622240
AN - SCOPUS:0037284046
VL - 58
SP - 135
EP - 142
JO - Zeitschrift fur Naturforschung. Teil C: Biochemie, Biophysik, Biologie, Virologie
JF - Zeitschrift fur Naturforschung. Teil C: Biochemie, Biophysik, Biologie, Virologie
SN - 0939-5075
IS - 1-2
ER -