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)

We evaluated the relationship between cell pH and cGMP production in cultured rat renal inner medullary collecting duct cells. The cGMP level, 21 +/- 6, was not different in control vs. alkalinized cells, 49 +/- 17 fmol/mg protein (p greater than 0.5). 10(-11) M atrial natriuretic peptide (ANF) enhanced cGMP production in alkalinized cells, 426 +/- 34 vs. 141 +/- 9*. Conversely, alkalinization inhibited 10(-4)M nitroprusside (SNP) induced cGMP formation, 29 +/- 9 vs. 332 +/- 67*. Phosphodiesterase inhibition abolished the difference in cGMP production by ANF but did not reverse the inhibitory effect of alkalinization on SNP induced cGMP production. In rat renal inner medullary collecting duct cells, cellular alkalinization plays a significant role in the regulation of guanylate cyclase mediated cGMP production. * = p less than 0.05).
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PMID:Regulation of cGMP production by intracellular alkalinization in cultured rat inner medullary collecting duct cells. 216 12

Frame-shift mutations within the C terminus of aquaporin 2 (AQP2) cause autosomal-dominant nephrogenic diabetes insipidus (AD-NDI). To identify the molecular mechanism(s) of this disease in vivo and to test possible therapeutic strategies, we generated a mutant AQP2 (763-772 del) knockin mouse. Heterozygous knockin mice showed a severely impaired urine-concentrating ability. However, they were able to slightly increase urine osmolality after dehydration. This milder phenotype, when compared with autosomal-recessive NDI, is a feature of AD-NDI in humans, thus suggesting successful establishment of an AD-NDI mouse model. Immunofluorescence of collecting duct cells in the AD-NDI mouse revealed that the mutant AQP2 was missorted to the basolateral instead of apical plasma membrane. Furthermore, the mutant AQP2 formed a heterooligomer with wild-type AQP2 and showed a dominant-negative effect on the normal apical sorting of wild-type AQP2 even under dehydration. Using this knockin mouse, we tested several drugs for treatment of AD-NDI and found that rolipram, a phosphodiesterase 4 inhibitor, was able to increase urine osmolality. Phosphodiesterase inhibitors may thus be useful drugs for the treatment of AD-NDI. This animal model demonstrates that a mutant monomer gains a dominant-negative effect that reverses the normal polarized sorting of multimers.
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PMID:Pathogenesis and treatment of autosomal-dominant nephrogenic diabetes insipidus caused by an aquaporin 2 mutation. 1696 83