Sister of P-glycoprotein

S. J., Helgason, C. D., Ackerley, C., Phillips, M. J., Ling, V., Targeted inactivation of sister of P-glycoprotein gene (spgp) in mice results in nonprogressive but persistent intrahepatic cholestasis, Proc. Natl. Acad. Sci. USA 2001, 98, 2011-2016. 

The sister of P-glycoprotein represents the canalicular bile salt export pump of mammalian liver. J Biol Chem 1998 ... 

Lecureur V, Sun D, Hargrove P, Schuetz EG, Kim RB, Lan LB et al. Cloning and expression of murine sister of P-glycoprotein reveals a more discriminating transporter than MDRl/P-glyco-protein. Mol Pharmacol 2000 57(1) 24— 35. 

Torok M, Gutmann H, Fricker G, et al. Sister of P-glycoprotein expression in different tissues. Biochem Pharmacol 1999 57(7) 833—835. 

Gerloff, T., B. Stieger, B. Hagenbuch, J. Madon, L. Landmann, J. Roth, A.F. Hofmann and PJ. Meier. The sister of P-glycoprotein represents the canalicular bile salt export pump of mammalian fiver. J. Biol. Chem. 273 10046-10050, 1998. 

BSEP also known as sister-P-glycoprotein (SPGP) was originally cloned from pig liver (185). BSEP is localized on the canalicular membrane of hepa-tocytes and is responsible for the secretion of bile salts across the canalicular membrane into bile. BSEP appears to be the predominant bile salt efflux system for hepatocytes, and is a critical component in the enterohepatic circulation of bile acids. A number of mutations in the transporter were found to the basis for progressive familial intrahepatic cholestasis type 2 (PFIC2) (186-188). Mutations found in PFIC2 patients include frameshifts, missense mutations, and premature termination codons. Most PFIC2 patients lack immunohistochemically detectable BSEP in their liver. Recently, seven... 

Wang E-j, Casciano CN, Clement RP, Johnson WW. Fluorescent substrates of sister-P-glycoprotein (BSEP) evaluated as markers of active transport and inhibition evidence for contingent unequal binding sites. Pharm Res 2003 20 537-544. 

Another ABC transporter is sister P-glycoprotein, otherwise called the bile salt export pump (BSEP or ABCBl 1). It has been suggested that inhibition of this pump may increase the risk of cholestasis, see Drug transporters under Drug excretion interactions , (p.7). 

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