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Volumn 6, Issue 5, 1996, Pages 610-617

P-glycoprotein and multidrug resistance

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE TRIPHOSPHATASE; ADENOSINE TRIPHOSPHATE; ANTINEOPLASTIC AGENT; CARRIER PROTEIN; CHLORIDE CHANNEL; GLYCOPROTEIN P;

EID: 0005014240     PISSN: 0959437X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0959-437X(96)80091-8     Document Type: Article
Times cited : (523)

References (65)
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    • of special interest. This review summarizes the work on volume-activated chloride channel activity associated with P-glycoprotein. Both the views - including the earlier one proposing that P-glycoprotein itself is a chloride channel and the more recent observations (see [51]) suggesting that it is instead a regulator of the volume-activated chloride channel activity - are covered. The role of P-glycoprotein as either a chloride channel or its modulator, however, is still very controversial (see also [52]).
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    • of special interest. In this article, evidence is presented that P-glycoprotein itself does not function as a volume-activated chloride channel; instead, the phosphorylation of P-glycoprotein by PKC regulates the activity of an endogenous chloride channel. The role of PKC mediated phosphorylation is confirmed by the mutagenesis of serine and threonine residues in the consensus phosphorylation sites in the linker region of P-glycoprotein.
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    • Hardy, S.P.1    Goodfellow, H.R.2    Valverde, M.A.3    Gill, D.R.4    Sepulveda, V.5    Higgins, C.F.6
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    • of special interest. Evidence is presented here that endogenously expressed P-glycoprotein in a human small intestinal epithelial cell line neither functions as a volume-activated chloride channel nor as a PKC mediated modulator of the chloride channel. The volume-activated chloride channel activity is not inhibited by P-glycoprotein specific antibodies or by its substrates and modulators. These findings, thus, bring into question the proposed association of P-glycoprotein with the chloride channel.
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    • of special interest. This article reports the presence of a multiorganic anion transporter, MOAT, in the canalicular (apical) membranes of rat hepatocytes. The rat MOAT is a liver-specific homolog of human MRP and is involved in the hepatobiliary secretion of bilirubin glucuronides and other conjugated organic anions.
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    • Paulusma, C.C.1    Bosma, P.J.2    Zaman, G.J.R.3    Bakker, C.T.M.4    Otter, M.5    Scheffer, G.L.6    Scheper, R.J.7    Borst, P.8    Oude Elferink, R.P.9
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    • of outstanding interest. This review deals with the overlapping tissue distribution and substrate specificities of P-glycoproteins and cytochrome P450 3A. Several tumor samples show a concomitant increase in expression of P-glycoprotein as well as isozyme 3A of cytochrome P450. Several anticancer hydrophobic drugs, calcium channel blockers, flavonoids, immunosuppressive agents and hormones, such as dexamethasone, hydrocortisone and progesterone, exhibit affinity toward both proteins. The similarities in drug recognition between P-glycoprotein and cytochrome P450 3A are not widely recognized. They do, however, present unique challenges in understanding pharmacokinetics of drug absorption, metabolism and excretion.
    • Wacher VJ, Wu CY, Benet LZ. Overlapping substrate specificities and tissue distribution of cytochrome P450 3A and P-glycoprotein: implications for drug delivery and activity in cancer chemotherapy. of outstanding interest Mol Carcinog. 13:1995;129-134 This review deals with the overlapping tissue distribution and substrate specificities of P-glycoproteins and cytochrome P450 3A. Several tumor samples show a concomitant increase in expression of P-glycoprotein as well as isozyme 3A of cytochrome P450. Several anticancer hydrophobic drugs, calcium channel blockers, flavonoids, immunosuppressive agents and hormones, such as dexamethasone, hydrocortisone and progesterone, exhibit affinity toward both proteins. The similarities in drug recognition between P-glycoprotein and cytochrome P450 3A are not widely recognized. They do, however, present unique challenges in understanding pharmacokinetics of drug absorption, metabolism and excretion.
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    • Wacher, V.J.1    Wu, C.Y.2    Benet, L.Z.3
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