Background: P-glycoprotein (Pgp) is an ATP-dependent, integral plasma-membr
ane efflux pump that is constitutively expressed on (i) adult apical brush-
herder epithelial cells of the intestine, iii) the bile canalicular face of
hepatocytes, and (iii) the brush border epithelium of renal proximal tubul
es, This Pgp tissue distribution and localization affects the absorption, d
istribution, metabolism, and excretion of Pgp substrates, Little is known r
egarding the ontogeny of Pgp expression in these tissues.
Methods: Postnatal expression of Pgp on brush border membranes of small int
estine, Liver, and kidney as a function of maturity from birth through adul
thood was determined using Western immunoblotting and immunohistochemical t
echniques. Tissue was isolated from FVB mice at four different ages: day of
life 0 (D0), day of life 7 (D7, day of life 21 (D21), and adult (Ad). The
relative expression of Pgp protein on Western immunoblots was assessed by s
canning densitometry and indexed as a percentage (mean+/-SEM) of the adult
levels,
Results: On Western immunoblots, Pgp expression was limited at birth (19+/-
6% of Ad) and increased significantly with maturation in intestine (ANOVA,
P<0.005). In contrast, hepatic (113+/-12% of Ad) and renal (96+/-15% of Ad)
Pgp expression were at adult levels at birth. The tissue-specific developm
ental pattern of Pgp expression was confirmed by immunohistochemistry,
Conclusions: We conclude that Pgp is expressed in a tissue-specific and dev
elopmentally regulated fashion and speculate that developmental modulation
of intestine-Pgp expression may affect the oral bioavailability of Pgp subs
trates.