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)

The multisubunit vacuolar-type proton-translocating ATPases (H(+)-ATPases) mediate the acidification of various intracellular organelles. In a subset of tissues, they also mediate H(+) secretion at the plasma membrane. Two isoforms of the H(+)-ATPase B-subunit exist in humans; we have shown that mutations in ATP6V1B1, encoding the B1-isoform, cause the clinical condition distal renal tubular acidosis. Here we report the cloning and characterization of murine Atp6v1b1, which encodes a 513-amino acid (aa) protein with 93% identity to human ATP6V1B1. Genomic organization is conserved between the murine and human H(+)-ATPase B1-subunits, and Atp6v1b1 maps to a region of mouse chromosome 6 syntenic to human 2p13, the location of ATP6V1B1. Northern blotting detects a 2.2-kb Atp6v1b1 transcript in the kidney and testis, but not other major organs. In mouse kidney, the B1-subunit localizes to intercalated cells of the cortical and medullary collecting duct. B1 protein levels were not increased in either mouse renal cortex or medulla after either 2 or 7 days of oral acid loading. These results demonstrate that Atp6v1b1 encodes the murine ortholog of human ATP6V1B1 and provides a tool for future development of animal models based on manipulation of the Atp6v1b1 genomic locus.
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PMID:Molecular cloning and characterization of Atp6v1b1, the murine vacuolar H+ -ATPase B1-subunit. 1458 95

Metabolic alkalosis is a common feature of hypokalemic hypertensive syndromes associated with angiotensin II excess. The alkalosis-generating effect of angiotensin II is usually ascribed to its stimulatory effect on aldosterone secretion, a hormone that upregulates collecting duct hydrogen ion secretion. We studied the effect of angiotensin II infusions on the expression of B1 and a4 protein, subunits of the renal H+-ATPase in adrenalectomized rats. Adrenalectomized rats were given either angiotensin II or vehicle for 7 days via osmotic mini-pumps. H+-ATPase B1 protein expression was evaluated by Western blot analysis in isolated medulla and cortex plasma membrane preparations from one kidney, whereas the contralateral kidney was used for immunostaining. By Western blotting, the relative abundance of B1 protein was 2-fold higher in renal medulla membranes from rats with intact adrenal glands (sham surgery) than from adrenalectomized rats (219+/-47%, n=12; P<0.05). In contrast to renal medulla, adrenalectomy did not significantly alter the relative abundance of B1 protein in renal cortex. Angiotensin II also did not significantly alter the relative levels of B1 protein in the cortex, but it increased it significantly in renal medullary membranes (231+/-56%, n=8; P<0.005). Moreover, enhanced H+-ATPase B1 subunit protein immunoreactivity was found in medullary collecting duct segments of rats infused with angiotensin II. In contrast to B1, expression of a4, another subunit of the H+-ATPase was not altered by adrenalectomy or angiotensin II. We conclude that adrenalectomy decreases whereas angiotensin II increases H+-ATPase B1 subunit expression in medullary, but not in cortical collecting ducts. By increasing the relative abundance of the B1 subunit of H+-ATPase in the collecting duct, angiotensin II excess may lead to increased hydrogen ion secretion and thus metabolic alkalosis-a common feature of hypertensive syndromes associated with angiotensin II overactivity.
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PMID:Angiotensin II increases H+-ATPase B1 subunit expression in medullary collecting ducts. 1569 54