Detection and induction of P-glycoprotein isoforms in the rat small intestine⁺

Endogenous P-glycoprotein (Pgp) in the small intestine pumps drugs from the seral side to the luminal side. Induction of intestinal P-glycoprotein may decrease drug absorption and localize drugs. In this study, the isolorm- selective induction of Pgp was investigated in the rat intestine. Rats were treated with dexamethasone at 3 mg/kg dose daily for 3 days or estradiol at 10 mg/kg daily for 6 days. Pgp in the brush border membrane was detected by Western blotting. mRNA of Pgp isoforms was detected by RT-PCR. In control rats, only Pgp1 was detected in the jejunum and all 3 isoforms of Pgp were detected in the ileum. Dexamethasone induced Pgp1 and Pgp2 in the jejunum and induced Pgp1 in the ileum. Estradiol induced Pgp1 in the jejunum and Pgp2 in the ileum. Both dexamethasone and estradiol down-regulate Pgp3 in the ileum.