Localization of mRNA expression of P-glycoprotein at the blood-brain barrier and in the hippocampus.
The multidrug resistance (mdr) P-glycoprotein is an energy-dependent efflux transporter that protects the brain against a wide variety of neurotoxic compounds. This transmembrane protein is a well-known functional component of the blood-brain barrier and might be present in other brain cells as well. We have developed a riboprobe against the murine mdr1 mRNA recognizing both isoforms of the rodent mdr1 gene to determine the exact localization of P-glycoprotein expression. We have also studied the effects of treatment with a known inducer of P-glycoprotein expression. In situ mRNA hybridization demonstrates that mdr1 mRNA is present in the endothelial cells of brain capillaries throughout the rat brain, indicating that P-glycoprotein is expressed at the endothelial cells forming the blood-brain barrier. Surprisingly, specific mdr1 mRNA expression was also found in neuronal layers of hippocampal fields, particularly in the granule cells of the dentate gyrus. Kainic acid treatment decreased the expression levels of mdr1 mRNA in the dentate gyrus 6 and 24 h after treatment. Our data indicate that P-glycoprotein is expressed by endothelial cells and possibly dentate gyrus neurons The functional role of P-glycoprotein at dentate gyrus neurons is presently unknown.
Karssen
A M
AM
Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research/Leiden University Medical Center, The Netherlands. akarssen@stanford.edu
Meijer
O
O
Pons
D
D
De Kloet
E R
ER
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000096:biosynthesis / Q000235:genetics; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis*; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology*; D006854:Hydrocortisone / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D015347:RNA Probes; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D015347:RNA Probes; D012333:RNA, Messenger; C095122:multidrug resistance protein 3; D006854:Hydrocortisone