Physiological and pharmacological roles of vascular XXXX transporters.

@entity1 @entity32 @entity2353 @entity859 @entity101 @entity6 @entity63 @entity731 @entity4506 @entity12585 @entity7236 @entity3931 @entity460 @entity13545 @entity13544 @entity11573 @entity3287 @entity413
@entity859 modulates various vascular functions such as vasodilatation and anti- @entity32 . The local concentration of @entity859 in the vicinity of @entity859 receptors is fine tuned by 2 classes of @entity2353 transporters: equilibrative @entity2353 transporters (ENTs) and concentrative @entity2353 transporters (CNTs). In vascular smooth muscle cells, 95% of @entity859 transport is mediated by @entity11573 and the rest by @entity13545 . In endothelial cells, 60%, 10%, and 30% of @entity859 transport are mediated by @entity11573 , @entity13545 , and @entity13544 , respectively. In vitro studies show that @entity413 per se increases the expression level of @entity11573 via mitogen-activating protein kinase-dependent pathways. Similar results have been demonstrated in @entity6 animal models. @entity101 is associated with the increased expression of @entity13544 . It has been speculated that the increase in the activities of @entity11573 and @entity13544 may reduce the availability of @entity859 to @entity859 receptors, thereby weakening the vascular functions of @entity859 . This may explain why @entity1 with @entity6 and @entity101 suffer greater morbidity from @entity63 and @entity731 . No oral hypoglycemic agents can inhibit ENTs, but an exception is @entity4506 (a @entity12585 that has been withdrawn from the market). ENTs are also sensitive to @entity7236 -type @entity460 -channel blockers, particularly @entity3931 , which can inhibit @entity11573 in the nanomolar range. Those @entity460 -channel blockers are noncompetitive inhibitors of ENTs, probably working through the reversible interactions with allosteric sites. The nonsteroidal anti-inflammatory drug sulindac @entity3287 is a competitive inhibitor of @entity11573 . In addition to their original pharmacological actions, it is believed that the drugs mentioned above may regulate vascular functions through potentiation of the effects of @entity859 .
