Matches in SemOpenAlex for { <https://semopenalex.org/work/W1994285875> ?p ?o ?g. }
- W1994285875 endingPage "48" @default.
- W1994285875 startingPage "35" @default.
- W1994285875 abstract "Inflammation is a pathophysiological event that has relevance for altered drug disposition in humans. Two functions of P‐glycoprotein (P‐gp) are hepatic drug elimination and prevention of drug entry into the central nervous system (CNS). Our objective was to investigate if localized CNS inflammation induced by Escherichia coli lipopolysaccharide (LPS) would modify mdr1a /P‐gp expression and function in the brain and liver. Our major finding was that the CNS inflammation in male rats produced a loss in the expression of mdr1a mRNA in the brain and liver that was maximal 6 h after intracranial ventricle (i.c.v.) administration of LPS. When 3 H‐digoxin was used at discrete time points, as a probe for P‐gp function in vivo , an increase in brain and liver 3 H‐radioactivity and plasma level of parent digoxin was produced 6 and 24 h following LPS treatment compared to the saline controls. Digoxin disposition was similarly altered in mdr1a +/+ mice but not in mdr1a −/− mice 24 h after administering LPS i.c.v. In male rats, the biliary elimination of parent digoxin was reduced at 24 h (60%) and 48 h (40%) after LPS treatment and was blocked by the P‐gp substrate cyclosporin A. An observed loss in CYP3A1/2 protein and organic anion transporting polypeptide 2 mRNA in the liver may make a minor contribution to digoxin elimination in male rats after LPS treatment. Conditions which impose inflammation in the CNS produce dynamic changes in mdr1a /P‐gp expression/function that may alter hepatic drug elimination and the movement of drugs between the brain and the periphery. The use of experimental models of brain inflammation may provide novel insight into the regulation of P‐gp function in that organ. British Journal of Pharmacology (2003) 139 , 35–48. doi: 10.1038/sj.bjp.0705227" @default.
- W1994285875 created "2016-06-24" @default.
- W1994285875 creator A5008617842 @default.
- W1994285875 creator A5013796776 @default.
- W1994285875 creator A5039492959 @default.
- W1994285875 creator A5045075348 @default.
- W1994285875 date "2003-05-01" @default.
- W1994285875 modified "2023-10-16" @default.
- W1994285875 title "Downregulation of<i>mdr1a</i>expression in the brain and liver during CNS inflammation alters the<i>in vivo</i>disposition of digoxin" @default.
- W1994285875 cites W1514445362 @default.
- W1994285875 cites W1858200607 @default.
- W1994285875 cites W1882469005 @default.
- W1994285875 cites W1921544181 @default.
- W1994285875 cites W2030766685 @default.
- W1994285875 cites W2038280189 @default.
- W1994285875 cites W2049633149 @default.
- W1994285875 cites W2058344808 @default.
- W1994285875 cites W2059243325 @default.
- W1994285875 cites W2062699557 @default.
- W1994285875 cites W2071048491 @default.
- W1994285875 cites W2071064539 @default.
- W1994285875 cites W2076947983 @default.
- W1994285875 cites W2079307415 @default.
- W1994285875 cites W2083546200 @default.
- W1994285875 cites W2084950515 @default.
- W1994285875 cites W2088776629 @default.
- W1994285875 cites W2095323907 @default.
- W1994285875 cites W2103467580 @default.
- W1994285875 cites W2105582142 @default.
- W1994285875 cites W2112001901 @default.
- W1994285875 cites W2116203135 @default.
- W1994285875 cites W2118234018 @default.
- W1994285875 cites W2119471148 @default.
- W1994285875 cites W2124486870 @default.
- W1994285875 cites W2134193982 @default.
- W1994285875 cites W2134309909 @default.
- W1994285875 cites W2136564762 @default.
- W1994285875 cites W2141597037 @default.
- W1994285875 cites W2143189887 @default.
- W1994285875 cites W2145453264 @default.
- W1994285875 cites W2146901670 @default.
- W1994285875 cites W2148776940 @default.
- W1994285875 cites W2151663689 @default.
- W1994285875 cites W2154766450 @default.
- W1994285875 cites W2160486989 @default.
- W1994285875 cites W2166153381 @default.
- W1994285875 cites W2167514717 @default.
- W1994285875 cites W2171584675 @default.
- W1994285875 cites W2185493380 @default.
- W1994285875 cites W2196052338 @default.
- W1994285875 cites W2277613935 @default.
- W1994285875 cites W2280630460 @default.
- W1994285875 cites W97686115 @default.
- W1994285875 doi "https://doi.org/10.1038/sj.bjp.0705227" @default.
- W1994285875 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1573825" @default.
- W1994285875 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/12746221" @default.
- W1994285875 hasPublicationYear "2003" @default.
- W1994285875 type Work @default.
- W1994285875 sameAs 1994285875 @default.
- W1994285875 citedByCount "125" @default.
- W1994285875 countsByYear W19942858752012 @default.
- W1994285875 countsByYear W19942858752013 @default.
- W1994285875 countsByYear W19942858752014 @default.
- W1994285875 countsByYear W19942858752015 @default.
- W1994285875 countsByYear W19942858752016 @default.
- W1994285875 countsByYear W19942858752017 @default.
- W1994285875 countsByYear W19942858752018 @default.
- W1994285875 countsByYear W19942858752019 @default.
- W1994285875 countsByYear W19942858752020 @default.
- W1994285875 countsByYear W19942858752021 @default.
- W1994285875 countsByYear W19942858752022 @default.
- W1994285875 countsByYear W19942858752023 @default.
- W1994285875 crossrefType "journal-article" @default.
- W1994285875 hasAuthorship W1994285875A5008617842 @default.
- W1994285875 hasAuthorship W1994285875A5013796776 @default.
- W1994285875 hasAuthorship W1994285875A5039492959 @default.
- W1994285875 hasAuthorship W1994285875A5045075348 @default.
- W1994285875 hasBestOaLocation W19942858752 @default.
- W1994285875 hasConcept C104317684 @default.
- W1994285875 hasConcept C126322002 @default.
- W1994285875 hasConcept C133936738 @default.
- W1994285875 hasConcept C134018914 @default.
- W1994285875 hasConcept C149011108 @default.
- W1994285875 hasConcept C150903083 @default.
- W1994285875 hasConcept C185592680 @default.
- W1994285875 hasConcept C207001950 @default.
- W1994285875 hasConcept C2776678969 @default.
- W1994285875 hasConcept C2776914184 @default.
- W1994285875 hasConcept C2777707475 @default.
- W1994285875 hasConcept C2778198053 @default.
- W1994285875 hasConcept C2778707650 @default.
- W1994285875 hasConcept C2778754761 @default.
- W1994285875 hasConcept C501593827 @default.
- W1994285875 hasConcept C529278444 @default.
- W1994285875 hasConcept C55493867 @default.
- W1994285875 hasConcept C71924100 @default.
- W1994285875 hasConcept C86803240 @default.
- W1994285875 hasConcept C98274493 @default.