Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent studies showed that coexpression of Kir6.1 or Kir6.2 with the sulfonylurea receptor (SUR1, SUR2A, or SUR2B) reconstituted an inwardly rectifying, ATP-sensitive K(+) channel that was inhibited by glibenclamide (2, 15-17). Here we report the isolation of a rat homolog of mouse SUR2B (denoted rSUR2B) from a rat kidney cDNA library. The rSUR2B sequence contains a 4,635-bp open reading frame that encodes a 1,545-amino acid polypeptide, showing 67% shared identity with SUR1 (a pancreatic beta-cell isoform) and 98% with both SUR2A (a brain isoform) and SUR2B (a vascular smooth muscle isoform). Consistent with the predicted structures of other members of the ATP-binding cassette (ABC) superfamily, the sequence of rSUR2B contains 17 putative membrane-spanning segments. Also, predicted Walker A and B consensus binding motifs, present in other ABC members, are conserved in the rSUR2B sequence. RT-PCR revealed that rSUR2B is widely expressed in various rat tissues including brain, colon, heart, kidney, liver, skeletal muscle, and spleen. The intrarenal distribution of the rSUR2B transcript was investigated using RT-PCR and Southern blot of microdissected tubules. The rSUR2B transcript was detected in proximal tubule, cortical thick ascending limb, distal collecting tubule, cortical collecting duct, and outer medullary collecting duct, but not medullary thick ascending limb. This distal distribution overlaps with that of ROMK. Coexpression of rSUR2B with ROMK2 cRNA (in 1:10 ratio) in Xenopus laevis oocytes resulted in whole cell Ba(2+)-sensitive K(+) currents that were inhibited by glibenclamide (50% inhibition with 0.2 mM glibenclamide). In contrast, rSUR2B did not confer significant glibenclamide sensitivity to oocytes coinjected with ROMK1 or ROMK3. The interaction between ROMK2 and rSUR2B was further studied by coimmunoprecipitation of in vitro translated rSUR2B and ROMK2. In agreement with the functional data, the rSUR2B protein was coimmunoprecipitated with ROMK2 in the ROMK2-rSUR2B cotranslated samples. Our data demonstrate that ROMK2, but not ROMK1 and ROMK3, can interact with rSUR2B to confer a sulfonylurea-sensitive K(+) channel, implicating SUR proteins in forming and regulating renal ATP-sensitive K(+) channels. The ROMK isoform specificity of glibenclamide effects suggests that the NH(2) terminus of the ROMK protein mediates rSUR2B-ROMK2 interactions.
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PMID:Rat homolog of sulfonylurea receptor 2B determines glibenclamide sensitivity of ROMK2 in Xenopus laevis oocyte. 1075 Dec 28

Kir channel subunit expression during development of the rat collecting-duct epithelium was quantified by RT-PCR of primary monolayer cultures. mRNAs of the vascular-type K(ATP) (K(NDP)) channel-forming subunits Kir6.1/SUR2 were highly expressed in early ureteric bud generations (embryonic day E14) and downregulated thereafter, while Kir1.1b (ROMK2) mRNA increased fourfold during cortical collecting duct (CCD) maturation. As assessed by immunohistochemistry, Kir6.1 protein was abundant in the apical and basolateral plasma membranes of early ureteric buds and trunks (E15 to postnatal day P1), downregulated thereafter and not detectable in CCD and outer medullary collecting ducts (OMCD) (P7). During nephron development, Kir6.1 protein was expressed ubiquitously on plasma membranes of early nephron stages from mesenchymal condensations to S-shaped bodies. After fusion of nephron and CCD, Kir6.1 protein was restricted to the apical membrane of proximal tubule. The Kir6/SUR2 channel opener, pinacidil (100 microM/2 days), increased tubulogenesis in organ culture by a factor of 3. Cell proliferation of human embryonic kidney cells (HEK 293) which endogenously express Kir6.1/SUR2 mRNA was stimulated by pinacidil in a dose-dependent manner, an effect that was partially abolished by glibenclamide (3 microM). In summary, Kir6.1/SUR2 channel subunits are highly expressed during early development of ureteric bud and nephron epithelia where Kir6.1/SUR2 activity regulates cell proliferation.
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PMID:Developmental expression and functional significance of Kir channel subunits in ureteric bud and nephron epithelia. 1246 33

The mammalian metanephric kidney develops following a general principle of organogenesis of epithelial organs, i.e., along the tree-like structure of an arborizing ductal system (the ureteric bud and cortical collecting duct). In parallel, the proximal portions of the uriniferous tubule develop by mesenchymal-to-epithelial transition of the neighbouring mesenchyme. On one hand, vectorial transport systems in nephrogenesis should be functional at the onset of glomerular filtration in any of the newly formed nephron generations to prevent loss of salt, water and metabolites. On the other hand, developing nephron epithelia must serve the needs of organ-formation such as cell proliferation and fluid-secretion for morphogenic purposes. This review intends to summarize current data and concepts on the development of renal epithelial functions with an emphasis on ion channels. Current model systems are introduced, such as ureteric bud cell monolayer culture, in vitro nephron culture, HEK293 cell culture, and the dissection of tubular cells for direct analysis. The current data on the developmental expression and functions of ENaC Na(+) channels, the CFTR, ClC-2 Cl(ndash;) channels, L-type Ca(2+) channels, P2 purinoceptors, and the Kir6.1/SUR2, ROMK (Kir1.1), and Kv K(+) channels are presented.
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PMID:Development of renal function. 1635 83