CELLULAR-LOCALIZATION OF P-GLYCOPROTEIN IN BRAIN VERSUS GONADAL CAPILLARIES

P-glycoprotein, the multidrug resistance protein that actively transpo rts a wide variety of lipophilic substrates out of cancer cells, has r ecently been described in some normal tissues, including the endotheli um of the brain and testes. Here we show that P-glycoprotein is also e xpressed in ovarian endothelium. In ovarian capillaries, the immunolab eled protein was detected with two monoclonal antibodies to P-glycopro tein. It was shown to be membrane-bound and to transport a known P-gly coprotein substrate. Expression of P-glycoprotein in endothelial cells suggests that this transport protein plays a role in enhancing or res tricting vascular permeability to lipophilic molecules. If it does, th en its role may be predicted from its site of expression on the lumina l or abluminal face of the capillary wall. In the region of the endoth elial nucleus, endothelial membranes are sufficiently far apart that t hey can be distinguished at the light microscopic level. Confocal exam ination of tissue sections double labeled for P-glycoprotein and nucle i confirmed that, in brain, P-glycoprotein is expressed only on lumina l membranes. This location is consistent with its putative role in pro tecting the neuropil from circulating lipophilic molecules. In both te sticular and ovarian endothelium, however, P-glycoprotein is expressed on both luminal and abluminal membranes. This localization suggests t hat it acts to exclude P-glycoprotein substrates from the endothelial cells themselves.