Differential expressiion of transporters in the intestine and its applicatiion to regulation of the drug absorptioin

摘要

The present study was aimed to quantify the expression of mRNA of drug transportes,including PepT1,mrp2 and mdrl a in the small intestine and to examine the correlations between the expression and the tramsport activity.Variation in expression levels of transportes along the proximal-distal axis of the intestine was examined.Small intestine of starved and fed rats were removed and divided in eight segments and total RNAs isolated.In fed rats,yield of total RNA was constant among each segment,while the increase was observed in the upper part of small intesting of starved rats.Complementary DNA was prepared by reverse transciption of total RNA of each segment and real-time PCR was performed to quantify mRNA expressiion of various drug transporters.Experssion of PepT1 mRNA was lower in upper segment than that in lower segment.In starved rats,PetT1 expression was increased significantly in the middle part of the intestine.As for mrp2,the expression was higher in upper segment and lower in lower segment and the increase in the expression by the starvatioin was observed in each segment of the intestine.The mdr1a expression was increased gradually along the proximal-distal axis of the small intestine and there was no difference between starved and red rats.The actual number of PetT1 mRNA expressed in each segment was approximately 10-fold greater than that of mrp2 or mdr1a.The intestinal absorption of cefadroxil (CDX)in each segment at pH6.0 was measured using Ussing chamber.Permeability conefficient of CDX in jejunum was significantly coefficient of CDX under both fed and starved conditions.it is suggested that change in physiological and/or pharmacological state of the intestinal tissue may affect the expression and function of various transporters and thereby altars disposition of drugs.