. Expression, localization, and regulation of aquaporin-1 to -3 in rat urothelia. Am J Physiol Renal Physiol 282: F1034-F1042, 2002. First published January 29, 2002 10.1152/ajprenal.00136.2001.-Although mammalian urothelia are generally considered impermeable to constituents of urine, in vivo studies in several species indicate urothelial transport of water and solutes under certain conditions. This study investigates the expression, localization, and regulation of aquaporin (AQP)-1, -2, and -3 in ureteral and bladder tissues in 48-h dehydrated and water-loaded female Wistar rats. Immunoblots of homogenates of whole ureter and bladder identified characteristic ϳ28-and 35-to 44-kDa bands for AQP-1, -2, and -3. AQP-1 was localized to capillary and arteriole endothelial cells, whereas AQP-2 and -3 circumferentially lined the epithelial cell membranes except for the apical membrane of the epithelial cells adjacent to the lumens of both ureter and bladder. AQP-2 was also present in epithelial cell cytoplasm. Dehydration resulted in 160-200% increases of AQP-3 signal and 24-49% increases of AQP-2 signal but no change in AQP-1 signal on immunoblots of homogenates of ureters and bladders. AQPs in genitourinary tract urothelia likely play a role in the regulation of epithelial cell volume and osmolality and may play a role in bulk water movement across urothelia.Western blot analysis; immunocytochemistry; water transport IT IS GENERALLY ASSUMED THAT the mammalian lower urinary tract is an impermeable transit and storage system and that micturated urine is identical to that excreted by kidneys (7). In fact, recent in vitro studies have documented very low urothelial permeability to water, ions, and nonelectrolytes and demonstrated that a major permeability barrier resides in the apical luminal membrane of the epithelial cells ("umbrella cells") lining the bladder lumen (reviewed in Ref. 15;19).Although urothelial permeability to water and solutes may be low, it is finite, and the possibility that urine might be significantly modified in transit by the lower urinary tract is plausible given the large urothelial surface area and long elapsed time between egress of urine from collecting ducts and micturation. Indeed, significant net transport (both lumen to blood and blood to lumen) of solutes, including urea, creatinine, sodium, potassium, and chloride, usually down their respective blood/urine gradients, has been demonstrated in vivo in rabbits and rats and studies of perfused dog ureter (14, 29) and bladder (8,9,14,21,27). Furthermore, a number of studies have shown that rabbit and guinea pig urinary bladder epithelium contain an aldosterone-stimulated, amiloride-inhibited sodium transporter (2, 16), which has recently been identified by Northern blot analysis as the epithelial sodium channel (22). The epithelial sodium channel is known to be responsible for salt and fluid transport across epithelia of many tissues (6).Although isotopic movement of D 2 O or isotopically labeled water across mammalian urothelia has bee...
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