Identification of a P-Glycoprotein-Deficient Subpopulation in the CF-1 Mouse Strain Using a Restriction Fragment Length Polymorphism

The Presence of Xenobiotic Transporters in Rat Placenta

“…Moreover, the homozygous fetuses (ϩ/ϩ) with abundant P-gp were totally insensitive to the avermectin isomer. Umbenhauer et al (1997) further showed that enhanced fetal drug penetration paralleled the increased avermectin sensitivity in Mdr1a mutant fetuses. Furthermore, with the Mdr1a/Mdr1b knockout mouse model, Smit et al (1999) determined that the drug transporting P-gp at the fetoplacental unit serves to limit placental transfer of P-gp substrates such as digoxin, saquinavir, and paclitaxel from the maternal circulation to the fetus.…”

“…They showed that Mdr1a is present in the fetal-derived epithelial cells that make up the exchange border between the fetal and maternal blood circulation, with Mdr1a facing the maternal blood side. In naturally occurring Mdr1a mutant mice of the CF-1 outbred mouse stock that lack Mdr1a (Umbenhauer et al, 1997), P-gp is associated with enhanced sensitivity of the fetus to an isomer of the pesticide avermectin. Specifically, fetuses deficient in P-gp were 100% susceptible to cleft palate, FIG.…”

The Development of Drug Metabolism Research as Expressed in the Publications of ASPET: Part 3, 1984–2008

“…9 P-glycoprotein was found to control the penetration of many drugs into the brain (Schinkel et al, 1994). Umbenhauer and coworkers showed that a genetic deficiency in P-glycoprotein was correlated with the penetration of avermectin into the brain in mice (Umbenhauer et al, 1997;Kwei et al, 1999).…”

Protein model for pollutant uptake and elimination by living organisms and its implications for ecotoxicology

“…The actions of some of these underlie major medical problems, including antibiotic and multi-drug resistance (MDR), as well as biocide resistance in pest and weed species (Alberts et al 1994, Schäfer et al 1996, Al-Awqati 1999, Closs et al 2000, Stevens et al 2000, Thumser & Storch 2000, Ueda & Matsuk 2000, Chaumont et al 2001, Garcia et al 2001, Hu & Wu 2001, Marples 2001, Nejsum et al 2001, Sansom & Law 2001, Zeuthen et al 2001, Raggers et al 2002, Madigan et al 2003. Ivermectin, a lipophilic drug toxic to helminths, is tolerated by mammals if their cells can rapidly synthesise the appropriate proteins to eliminate the drug (Schinkel et al 1994, Umbenhauer et al 1997, Smith & Pritchard 2002. The ubiquitous large ABC superfamily of exporters is well known (van Veen et al 2000).…”