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)

Previous studies from our laboratory have determined that inner medullary collecting duct (IMCD) cells express a novel DA2-like dopamine receptor (namely, DA2K) that is linked to prostaglandin E2 (PGE2) production. In the present study, we have further characterized the dopamine-stimulated PGE2 response. Dopamine stimulated PGE2 production in cultured IMCD cells dose dependently (concentration for half-maximal stimulation, 11.1 microM; maximal stimulation, 235.1% of basal), an effect that was blocked by the DA2 antagonists domperidone and (S)-(-)-3-iodo-2-hydroxy-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl)-methyl] benzamine. Inhibition of intracellular calcium release with 8-(diethylamino)-octyl-3,4,5-trimethoxybenzoate hydrochloride (100 microM) blocked the dopamine response, whereas voltage-dependent calcium-channel blockers had no effect. Inhibition of phospholipase A2 (PLA2) activity with quinacrine (100 microM) completely blocked the dopamine-stimulated PGE2 production, whereas inhibition of polyphosphoinositol hydrolysis with neomycin (100 microM) or inhibition of protein kinase C with 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (10 microM) did not. Pertussis toxin (PT) treatment completely blocked the dopamine-stimulated PGE2 production but not the arachidonic acid-stimulated PGE2 production. These results suggest that dopamine, acting through the DA2K receptor, may be an important regulator of PGE2 production in IMCD cells. Furthermore, our results are most consistent with either a direct interaction of the DA2K receptor with PLA2 through a PT-sensitive G protein or an indirect interaction with PLA2 through mobilization of intracellular calcium.
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PMID:Prostaglandin E2 production in rat IMCD cells. I. Stimulation by dopamine. 183 85

Volume changes and cytosolic Ca2+ concentration ([Ca2+]i) of inner medullary collecting duct (IMCD) cells under hypotonic stress were monitored by means of confocal laser scanning microscopy and fura 2 fluorescence, respectively. Reduction of extracellular osmolality from 600 to 300 mosmol/kgH2O by omission of sucrose led to an increase in cell volume within 1 min to 135 +/- 3% (n = 9), followed by a partial regulatory volume decrease (RVD) to 109 +/- 2% (n = 9) within the ensuring 5 min. In parallel, [Ca2+]i rose from 145 +/- 9 to 433 +/- 16 nmol/l (n = 9) and thereafter reached a lower steady state of 259 +/- 9 nmol/l. Under low-Ca2+ conditions (10 nmol/l) RVD was not impeded and reduction of osmolality evoked only a transient increase of [Ca2+]i by 182 +/- 22 nmol/l (n = 6). Preincubation with 100 mumol/l 8-(N,N-diethylamino)octyl-3,4,5-trimethoxy-benzoate hydrochloride (TMB-8) or 20 mmol/l caffeine, both effective inhibitors of Ca2+ release from intracellular stores, in low Ca2+ as well as in high Ca2+, inhibited the Ca2+ response and abolished RVD. The temporal relationship between Ca2+ release from intracellular stores and Ca2+ entry was analyzed by determining fura 2 quenching, using Mn2+ as a substitute for external Ca2+. Intracellular Ca2+ release preceded Mn2+ influx by 17 +/- 3 s (n = 10). Mn2+ influx persisted during the whole period of exposure to hypotonicity, indicating that there is no time-dependent Ca2+ channel inactivation. Preincubation with TMB-8 or caffeine reduced Mn2+ influx to the control level, indicating that activation of Ca2+ channels in the plasma membrane occurs via intracellular Ca2+ release.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intracellular Ca2+ release and Ca2+ influx during regulatory volume decrease in IMCD cells. 804 53

1. Effects of prostaglandin E2 (PGE2) on ion transport were examined by observing the transmural (VT) and basolateral membrane voltage (VB) in the in vitro perfused rabbit connecting tubule (CNT) and the cortical collecting duct (CCD). 2. Addition of 1 microM PGE2 to the bath induced a biphasic response of transmural voltage (VT), with initial negative VT deflection followed by positive deflection in the CNT, but monophasic negative deflection in the CCD. Because PGE2 had no affect on the basolateral membrane voltage (VB), PGE2 mainly causes changes in the apical membrane voltage. 3. Elimination of Na+ from the lumen abolished the PGE2-induced VT response in the CNT. In the presence of 10 microM luminal amiloride, PGE2 caused only an initial negative deflection without causing later positive deflection. The positive VT deflection induced by PGE2 in the CCD was also blocked by luminal amiloride. 4. Addition of ouabain (0.1 mM) to the bath completely abolished the PGE2-induced VT changes in the CNT, indicating that an intact Na(+)-K+ pump is a prerequisite for the VT response to PGE2. 5. Addition of 2 mM Ba2+ to the lumen did not affect biphasic VT response to PGE2, indicating that Ba(2+)-sensitive K+ conductance is not involved. 6. Basolateral addition of 0.1 mM 8-(4-chlorophenylthio)-cAMP inhibited only the negative VT deflection induced by PGE2. 7. The positive VT deflection was blocked by basolateral addition of 50 microM 8-(N,N-diethylamino)octyl 3,4,5-trimethoxy benzoate hydrochloride (TMB-8), an inhibitor of intracellular Ca2+ release. But elimination of luminal Ca2+ did not affect the biphasic response to PGE2. 8. These findings suggest that the initial negative VT deflection is caused by an increase in Na+ influx across the luminal membrane through an amiloride-insensitive Na+ conductive pathway, whereas the later positive deflection is caused by the inhibition of Na+ influx through the amiloride-sensitive Na+ conductive pathway. The cAMP messenger system may be responsible for the initial negative deflection, whereas an increased intercellular Ca2+ release from the store is necessary for the later positive deflection caused by PGE2. The response in the CCD is comparable to the later response in the CNT.
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PMID:Effects of prostaglandin E2 on membrane voltage of the connecting tubule and cortical collecting duct from rabbits. 833 84

In this study we investigated the interrelationship between cell pH (pHi) and cell calcium (Cai) in cultured inner medullary collecting duct cells of the rat. Confluent monolayers were made quiescent by incubation for 24 h in Dulbecco's modified Eagle's medium supplemented with 0.1% serum before study. Changes in pHi and Cai were measured with the fluorescent probes 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein and fura 2. In nominally bicarbonate-free media containing 110 mM Na+ and 1 mM Cai, cell acidification to pH 6.70 increased Cai from 122 +/- 24 to 243 +/- 33 nM. In the absence of bath calcium, acidification increased Cai from 90 +/- 7 to 144 +/- 13 nM. An increase of pHi to 7.6 reduced Cai almost to baseline. Cell acidification increased inositol trisphosphate (IP3) production, and 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester, an IP3 antagonist, partially inhibited the rise in Cai. Elevation of Cai resulted in a sustained cell alkalinization from 7.32 +/- 0.02 to 7.58 +/- 0.04. When Cai was reduced, pHi fell to 7.25 +/- 0.01. We conclude that Cai and pHi participate in a feedback loop that modulates changes in each respective parameter.
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PMID:Interrelationship between cell pH and cell calcium in rat inner medullary collecting duct cells. 836 72

The nonapeptide bradykinin (BK) plays an important role in the production of eicosanoids within the collecting duct of the nephron. We have shown previously that BK can initiate a complex signaling cascade that causes the release of arachidonic acid (AA) from MDCK-D1 cells, a canine cell line of distal tubule and collecting duct origin. This release is dependent upon early activation of specific upstream enzymes, including phosphatidylcholine-specific phospholipase C (PC-PLC) and phospholipase D (PLD). Ultimately, the release of this precursor of eicosanoids is effected by recruitment of the cytoplasmic 85-kDa form of phospholipase A2 (cPLA2). This enzyme is thought to translocate from the cytosol to cellular membranes following stimulation by agonists that cause elevations of intracellular calcium ([Ca2+]i). The present study was undertaken to examine the dependence of AA release upon Ca2+ influx in BK-stimulated MDCK cells. For this purpose, cells were incubated with 1 microM BK for 1 min and lysed in Ca(2+)-free Tris buffer. The high-speed 100000 x g pellet was extracted with 10 mM octyl glucoside and the cPLA2 protein level was determined. Previous results from our laboratory indicated that BK induced a 1.81-fold increase in cPLA2 activity associated with cellular membranes, while in the present study, Western blotting with a specific cPLA2 antibody demonstrated a similar elevation in protein detected with these same membranes. A selective inhibitor of receptor-mediated Ca2+ entry, SK&F 96365, was used to resolve the role of extracellular Ca2+ in BK's ability to evoke AA release. Pretreatment of cells with SK&F 96365 resulted in an inhibition of greater than 60% of the BK response. Taken together, these results strongly suggest that BK-mediated AA release in MDCK-D1 cells is at least partly contingent upon translocation of cPLA2 to membranes initiated by an influx of extracellular Ca2+.
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PMID:Bradykinin-induced translocation of cytoplasmic phospholipase A2 in MDCK cells. 927 29