Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UNIPROT:P41181 (collecting duct)
5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the regulation by adenosine of a 305-pS chloride (Cl-) channel in the apical membrane of a continuous cell line derived from rabbit cortical collecting duct (RCCT-28A) using the patch clamp technique. Stimulation of A1 adenosine receptors by N6-cyclohexyladenosine (CHA) activated the channel in cell-attached patches. Phorbol 12,13-didecanoate and 1-oleoyl 2-acetylglycerol, activators of protein kinase C (PKC), mimicked the effect of CHA, whereas the PKC inhibitor H7 blocked the action of CHA. Stimulation of A1 adenosine receptors also increased the production of diacylglycerol, an activator of PKC. Exogenous PKC added to the cytoplasmic face of inside-out patches also stimulated the Cl- channel. Alkaline phosphatase reversed PKC activation. These results show that stimulation of A1 adenosine receptors activates a 305-pS Cl-channel in the apical membrane by a phosphorylation-dependent pathway involving PKC. In previous studies, we showed that the protein G alpha i-3 activated the 305-pS Cl- channel (Schwiebert et al. 1990. J. Biol. Chem. 265:7725-7728). We, therefore, tested the hypothesis that PKC activates the channel by a G protein-dependent pathway. In inside-out patches, pertussis toxin blocked PKC activation of the channel. In contrast, H7 did not prevent G protein activation of the channel. We conclude that adenosine activates a 305-pS Cl- channel in the apical membrane of RCCT-28A cells by a membrane-delimited pathway involving an A1 adenosine receptor, phospholipase C, diacylglycerol, PKC, and a G protein. Because we have shown, in previous studies, that this Cl- channel participates in the regulatory volume decrease subsequent to cell swelling, adenosine release during ischemic cell swelling may activate the Cl-channel and restore cell volume.
...
PMID:Adenosine regulates a chloride channel via protein kinase C and a G protein in a rabbit cortical collecting duct cell line. 131 18

Renal tubule solute and water transport is subject to regulation by numerous factors. To characterize direct effects of the recently discovered peptide endothelin (ET) on renal tubule transport, we determined signaling mechanisms for ET effects on vasopressin (AVP)-stimulated water permeability (PF) in rat terminal inner medullary collecting duct (IMCD) perfused in vitro. ET caused a rapid, dose-dependent, and reversible fall in AVP- but not cyclic AMP-stimulated PF, suggesting that its effect on PF is by inhibition of cyclic AMP accumulation. Indomethacin did not block ET actions, ruling out a role for prostaglandins in its effect. The protein kinase C (PKC) inhibitor calphostin, or pretreatment of perfused tubules with pertussis toxin, blocked ET-mediated inhibition of AVP-stimulated PF. ET caused a transient increase in intracellular calcium ([Ca2+]i) in perfused tubules, an effect unchanged in zero calcium bath or by PT pretreatment. ET effects on PF and [Ca2+]i desensitized rapidly. Inhibition of PF was transient and largely abolished by 20 min ET preexposure, and repeat exposure to ET did not alter [Ca2+]i. In contrast, PGE2-mediated inhibition of AVP-stimulated PF and increase of [Ca2+]i were sustained and unaltered by prior exposure of IMCD to ET. Thus desensitization to ET is homologous. We conclude that ET is a potent inhibitor of AVP-stimulated water permeability in rat terminal IMCD. Signaling pathways for its effects involve both an inhibitory guanine nucleotide-binding protein and phospholipase-mediated activation of PKC. Since ET is synthesized by IMCD cells, this peptide may be an important autocrine modulator of renal epithelial transport.
...
PMID:Endothelin inhibits vasopressin-stimulated water permeability in rat terminal inner medullary collecting duct. 132

In cultured cortical collecting duct (CCD) cells, exogenous prostaglandin E2 (PGE2) inhibited arginine vasopressin (AVP)-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) production in a concentration-dependent manner. Although pertussis toxin (PT, 500 ng/ml) alone did not reverse the PGE2-dependent inhibition, PT and staurosporine, a protein kinase C inhibitor, together partially reversed the effect of exogenous PGE2. In contrast, PT completely reversed the inhibition of AVP-dependent cAMP production by sulprostone. These data suggest that exogenous PGE2 can inhibit AVP-stimulated cAMP production and that the inhibitory effects of PGE2 are mediated by staurosporine- and PT-sensitive component(s). Short-term (15-240 min) incubation with phorbol 12-myristate 13-acetate (PMA, 10(-7) M) inhibited PGE2-stimulated cAMP production. Long-term (20 h) incubation with PMA augmented PGE2-stimulated cAMP production. These data provide evidence for the maintenance of a PT-sensitive PGE2-dependent inhibitory pathway of cAMP production in cultured CCD cells. In addition, data are presented that support an inhibitory role for protein kinase C in the effects of PGE2 on the metabolism of cAMP in these cells.
...
PMID:PGE2 regulates cAMP production in cultured rabbit CCD cells: evidence for dual inhibitory mechanisms. 133 88

The mechanism by which prostaglandin E2 (PGE2) inhibits sodium absorption (JNa) in the rabbit cortical collecting duct (CCD) was explored. PGE2 activates at least three signaling mechanisms in the CCD: (a) by itself PGE2 increases cAMP generation (b) PGE2 also inhibits vasopressin-stimulated cAMP accumulation, and (c) PGE2 raises intracellular calcium([Ca++]i). We tested the contribution of these signaling pathways to PGE2's effect on Na+ absorption, measuring 22Na flux (JNa) and [Ca++]i (using fura-2) in microperfused rabbit CCDs. In control studies PGE2 reduced JNa from 28.2 +/- 3.4 to 15.6 +/- 2.6 pmol.mm-1.min-1. Lowering bath calcium from 2.4 to 45 nM did not by itself alter JNa but in this setting PGE2 failed to inhibit JNa (28.6 +/- 5.4 to 38.5 +/- 4.0). In separate tubules, PGE2 raised [Ca++]i in a spike-like fashion followed by a sustained elevation. However, in 45 nM bath Ca++, PGE2 failed to produce a sustained [Ca++]i elevation. While pretreatment of CCDs with pertussis toxin blocked PGE2 inhibition of vasopressin-stimulated water permeability, it did not block the effect of PGE2 on JNa. To see if cAMP generation contributes to the effect of PGE2 on JNa, we tested the effect of exogenous cAMP, (8-chlorophenylthio(CPT)cAMP) on JNa. 0.1 mM 8-CPTcAMP reduced JNa from 35.75 +/- 2.3 to 21.6 +/- 2.2. However, the addition of PGE2 further blunted JNa to 15.9 +/- 1.3. In CCDs pretreated with indomethacin, 8-CPTcAMP did not significantly decrease JNa 33.6 +/- 2.8 vs. 28.4 +/- 2. However, superimposed PGE2 reduced JNa to 19.0 +/- 3.0. We conclude that PGE2 inhibits sodium transport predominantly by increasing intracellular calcium. This action is not mediated by a pertussis toxin-sensitive G protein. Finally, cAMP, through a cyclooxygenase-dependent mechanism, also inhibits CCD JNa and may contribute to the effects of PGE2 on JNa in the rabbit CCD.
...
PMID:Prostaglandin E2 inhibits sodium transport in rabbit cortical collecting duct by increasing intracellular calcium. 164 47

Atrial natriuretic peptide, acting through its second messenger guanosine 3',5'-cyclic monophosphate (cGMP), suppresses Na+ absorption across the renal inner-medullary collecting duct and increases urinary Na+ excretion. Patch clamp studies show that cGMP reduces Na+ absorption by inhibiting an amiloride-sensitive cation channel in the apical membrane. We have now examined, using the patch clamp technique, the molecular mechanisms of cGMP inhibition. Cyclic GMP directly and specifically reduced the probability of a single channel being open (open probability, Po) by 39% (inhibition constant, Ki = 7.6 x 10(-7) M) by a phosphorylation-independent mechanism. Cyclic GMP also inhibited the channel by activating cGMP-dependent protein kinase (cGMP-kinase). Exogenous cGMP-kinase completely inhibited the channel by a phosphorylation-dependent mechanism. Activation of a pertussis toxin-sensitive G protein by GTP-gamma-S blocked cGMP-kinase inhibition of the channel. By contrast, cGMP-kinase inhibition of Po was completely reversed by GTP-gamma-S. Taken together with the results of a previous study showing that a G protein activates the cation channel, these data indicate that cGMP-kinase and a G protein sequentially regulate the cation channel. Our results show that atrial natriuretic peptide, acting through cGMP, inhibits Na+ absorption across the inner-medullary collecting duct by a dual mechanism, and that cGMP-kinase inhibits the channel by a pathway involving a G protein.
...
PMID:Dual ion-channel regulation by cyclic GMP and cyclic GMP-dependent protein kinase. 169 Mar 55

One of the mechanisms by which Li evokes polyuria is thought to be impairment of arginine vasopressin (AVP)-sensitive adenylate cyclase (AdC) in cells of the renal collecting duct. To investigate how AdC is influenced by chronic administration of Li, we created nephrogenic diabetes insipidus (NDI) in rats and microdissected the medullary collecting tubule from both control and NDI rats. In the NDI group, the 10(-6) M AVP-stimulated cAMP contents failed to increase completely, and the levels were significantly lower than that of the control group (10.4 +/- 1.4 vs. 48.4 +/- 4.7 fmol/mm, P less than 0.001). Pretreatment with pertussis toxin (PT), an inhibitor of inhibitory G protein (Gi), did not affect the basal cAMP levels in both groups, although it increased AVP-stimulated cAMP production in the NDI group in a dose- and time-dependent manner. AVP-stimulated cAMP production with over 100 ng/ml PT in the NDI group reached the levels observed in the control group. Incubation with cholera toxin, an agonist of stimulatory G protein (Gs), increased the cAMP content in the two groups to almost equal levels. To exclude the possibility that prostaglandin E2 (PGE2) is involved in the cellular mechanism of Li-induced NDI, the effect of indomethacin (Indo) on PT action was examined. However, Indo (10(-5) M) did not influence either the basal or AVP-dependent cAMP contents. From these results it is suggested that Li impairs AVP-sensitive AdC not through inhibition of Gs but through activation of Gi and that PGE2 may not be involved in the cellular pathogenesis of NDI at least in the rat at the step of cAMP formation.
...
PMID:Cellular mechanism of lithium-induced nephrogenic diabetes insipidus in rats. 171 61

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.
...
PMID:Prostaglandin E2 production in rat IMCD cells. I. Stimulation by dopamine. 183 85

Epidermal growth factor (EGF) exhibits specific saturable binding to cultured rat inner medullary collecting tubule cells and stimulates inositol trisphosphate (IP3) production by these cells in a dose-dependent fashion. EGF-stimulated IP3 production is enhanced by GTP gamma s or AIF4- and is inhibited by GDP beta s or pertussis toxin. Alterations in extracellular Ca2+ have no effect on either basal or EGF-stimulated IP3 production. Similarly, treatment with EGTA which decreases cytosolic Ca2+ is without effect. In contrast, treatment with ionomycin which increases cytosolic Ca2+ has no effect on basal IP3 production but enhances the response to EGF. Activation of protein kinase C inhibits IP3 production in response to either EGF or AIF4-. These studies demonstrate the occurrence of EGF-stimulated phospholipase C activity in the rat inner medullary collecting duct. Stimulation by EGF is transduced by a pertussis toxin-sensitive G protein, unaffected by alterations in extracellular Ca2+, insensitive to a decrement in cytosolic Ca2+, enhanced by an increase in cytosolic Ca2+, and inhibited by protein kinase C.
...
PMID:Epidermal growth factor-stimulated phosphoinositide hydrolysis in cultured rat inner medullary collecting tubule cells. Regulation by G protein, calcium, and protein kinase C. 215 92

Administration of adenosine (Ado) into rat renal artery induces dose-dependent diuresis that is independent of changes in glomerular filtration rate or renal blood flow, suggesting a direct effect on tubule H2O reabsorption. To test the hypothesis that Ado modulates cellular action of arginine vasopressin (AVP) as a tubular mechanism for the diuretic effect of Ado, interaction of Ado with AVP was studied in primary cell culture of rat inner medullary collecting duct (IMCD) epithelium. Stimulation of cells with 10(-6) M AVP in presence of 0.1 mM Ro 20-1724, a nonmethylxanthine phosphodiesterase inhibitor that has no effect on Ado receptors, increased adenosine 3',5'-cyclic monophosphate (cAMP) levels twofold or more above baseline. Stimulation of cells with the A1 Ado-receptor agonist N6-cyclohexyladenosine (CHA), the A2-receptor agonist 5'-(N-ethylcarboxamido)-adenosine (NECA), or with the P-site agonist 2',5'-dideoxyadenosine (DDA) significantly inhibited the AVP-stimulated cAMP response. Preincubation with pertussis toxin abolished the inhibitory effects of CHA and NECA, but not of DDA. The data suggest that, in the rat IMCD, Ado modulates AVP action by interfering with its ability to stimulate formation of its second messenger, cAMP. This effect is mediated by the extracellular Ado receptors A1 and A2 and by the intracellular P-site. It occurs by at least two pathways, one sensitive and the other insensitive to pertussis toxin.
...
PMID:Interaction of adenosine with vasopressin in the inner medullary collecting duct. 217 61

We examined whether GTP binding proteins (G proteins) regulate sodium conducting channels in the apical membrane of renal inner medullary collecting duct (IMCD) cells and thereby modulate sodium absorption. Patch clamp studies were conducted on inside-out patches of the apical membrane of IMCD cells grown in primary culture. Guanosine 5'-triphosphate (GTP) and the nonhydrolyzable GTP analogue, GTP gamma S, which activate G proteins, increased the open probability of the cation channel. In contrast, the nonhydrolyzable GDP analogue, GDP beta S, which decreases G protein activity, inhibited the channel. Pertussis toxin also reduced the open probability of the channel. Addition of the alpha *i-3 subunit of Gi to the solution bathing the cytoplasmic surface of the membrane increased the open probability in a dose-dependent manner (2-200 pM). The threshold concentration for activation by alpha *i-3 was 2 pM. Activation of the cation channel by alpha *i-3 was not mediated via a protein kinase. The IMCD is the first polarized epithelium in which an ion channel has been shown to be directly regulated by a G protein. Thus, G proteins are important elements in regulating sodium absorption by the IMCD.
...
PMID:Guanine nucleotide-binding protein, alpha i-3, directly activates a cation channel in rat renal inner medullary collecting duct cells. 247 28


1 2 3 4 Next >>

---