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 previously reported that arginine vasopressin (AVP) stimulates the production of nitric oxide (NO) in inner medullary collecting duct (IMCD) via activation of V2 receptors (V2R) and the mobilization of intracellular Ca(2+). The aim of this study was to determine the pathway(s) through which this response is mediated. IMCDs were dissected from male Sprague-Dawley rats and intracellular Ca(2+) concentration ([Ca(2+)](i)) and NO production were measured using a fluorescence imaging system. AVP (100 nmol/l) produced a rapid increase [Ca(2+)](i) of 381 +/- 78 nmol/l that was followed by a significant increase of NO production (166 +/- 61%). The specific nonpeptide V2R antagonist OPC31260 (1 microM), but not the V1R antagonist OPC21268 (1 microM), inhibited the increase in [Ca(2+)](i) (up to 91 +/- 5%) and abolished the NO response to AVP. Both the phospholipase C inhibitor U73112 (3 microM) and the inositol (1,4,5) tri-phosphate 3 receptor blocker 2-APB (75 microM) reduced the peak [Ca(2+)](i) response to AVP (by 65 +/- 9 and 59 +/- 15%, respectively) and abolished the NO response. Although forskolin (100 microM; an activator of adenylyl cyclase) elicited a moderate increase in [Ca(2+)](i), neither preincubation with the adenylyl cyclase inhibitor 2'-5'-dideoxyadenosine (50 microM) nor the protein kinase A (PKA) inhibitor PKA(14-22) (100 microM) significantly inhibited peak [Ca(2+)](i) in response to AVP. IMCD [Ca(2+)](i) responses to AVP were reduced by 72 +/- 8% when incubated in Ca(2+)-free media and could be completely abolished by preincubation with the Ca(2+)-ATPase inhibitor thapsigargin. We conclude that AVP-induced NO production in IMCD is dependent on V2R activation of the phosphoinositide pathway and the mobilization of Ca(2+) from both intracellular and extracellular pools.
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PMID:Vasopressin-induced nitric oxide production in rat inner medullary collecting duct is dependent on V2 receptor activation of the phosphoinositide pathway. 1750 4

Under conditions of high dietary salt intake, prostaglandin E2 (PGE2) production is increased in the collecting duct and promotes urinary sodium chloride (NaCl) excretion; however, the molecular mechanisms by which PGE2 increases NaCl excretion in this context have not been clearly defined. We used the mouse inner medullary collecting duct (mIMCD)-K2 cell line to characterize mechanisms underlying PGE2-regulated NaCl transport. When epithelial Na(+) channels were inhibited, PGE2 exclusively stimulated basolateral EP4 receptors to increase short-circuit current (Isc(PGE2)). We found that Isc(PGE2) was sensitive to inhibition by H-89 and CFTR-172, indicating that EP4 receptors signal through protein kinase A to induce Cl(-) secretion via cystic fibrosis transmembrane conductance regulator (CFTR). Unexpectedly, we also found that Isc(PGE2) was sensitive to inhibition by BAPTA-AM (Ca(2+) chelator), 2-aminoethoxydiphenyl borate (2-APB) (inositol triphosphate receptor blocker), and flufenamic acid (FFA) [Ca(2+)-activated Cl(-) channel (CACC) inhibitor], suggesting that EP4 receptors also signal through Ca(2+) to induce Cl(-) secretion via CACC. Additionally, we observed that PGE2 stimulated an increase in Isc through crosstalk between cAMP and Ca(2+) signaling; BAPTA-AM or 2-APB inhibited a component of Isc(PGE2) that was sensitive to CFTR-172 inhibition; H-89 inhibited a component of Isc(PGE2) that was sensitive to FFA inhibition. Together, our findings indicate that PGE2 activates basolateral EP4 receptors and signals through both cAMP and Ca(2+) to stimulate Cl(-) secretion in IMCD-K2 cells. We propose that these signaling pathways, and the crosstalk between them, may provide a concerted mechanism for enhancing urinary NaCl excretion under conditions of high dietary NaCl intake.
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PMID:Prostaglandin E2 induces chloride secretion through crosstalk between cAMP and calcium signaling in mouse inner medullary collecting duct cells. 2428 92