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

The effects of selective alpha adrenoceptor agonists and antagonists on vasopressin (VP)-sensitive cyclic AMP (cAMP) formation in microdissected rat papillary collecting ducts were examined. In the presence of 10(-10) M VP, norepinephrine and the selective alpha-2 adrenoceptor agonist, B-HT 933, produced almost total inhibition of VP-stimulated cAMP accumulation. Half-maximal inhibition occurred at 1 x 10(-8) M and 6 x 10(-7) M for norepinephrine and B-HT 933, respectively. Cirazoline, a selective alpha-1 adrenoceptor agonist, had no significant effect on VP-stimulated cAMP accumulation. The inhibitory effects of norepinephrine and B-HT 933 were antagonized by rauwolscine but not by prazosin. The antagonism of B-HT 933-induced inhibition of VP-stimulated cAMP accumulation was competitive with an antagonist dissociation constant (KB) of 10.9 x 10(-9) M. Preincubation of papillary collecting ducts with pertussis toxin (1 microgram/ml for 1 hr at 37 degrees C) attenuated, by 65%, the inhibitory effect of B-HT 933 on VP-stimulated cAMP levels. These results demonstrate that alpha-2 adrenoceptors capable of inhibiting VP action are present on the papillary collecting duct. Furthermore, the alpha-2 adrenoceptor-induced inhibition of VP-stimulated cAMP accumulation is pertussis-toxin sensitive. This suggests that alpha-2 adrenoceptors are coupled negatively to adenylate cyclase, via the guanine nucleotide binding protein, in the collecting tubule.
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PMID:Inhibition of vasopressin-stimulated cyclic AMP accumulation by alpha-2 adrenoceptor agonists in isolated papillary collecting ducts. 289 53

The hormonal responsiveness profile of the cortical collecting duct varies from one species to another. To identify the hormones and agonists that modulate the functions of this tubule segment in the human species, we generated a cell line (HCD) immortalized by SV40 virus. The tubular origin of this cell line was assessed by the expression of collecting duct-specific antigens and the ability of vasopressin to increase by nine-fold cAMP synthesis. Glucagon and adenosine stimulated cAMP synthesis, and atrial natriuretic peptide stimulated cGMP synthesis in a concentration-dependent manner. Bradykinin, adenosine and angiotensin increased intracellular calcium concentration ([Ca2+]i). Because adenosine can regulate tubular functions, we examined its role on glucagon-induced cAMP synthesis. Using adenosine analogs, we demonstrated that HCT cells both expressed adenosine type-2 (A2) receptors which stimulated cAMP production, and adenosine type-1 (A1) receptors linked to [Ca2+]i increase which inhibited glucagon-stimulated cAMP synthesis. The inhibitory effect was abolished by pertussis toxin, and was neither due to [Ca2+]i increase nor to protein kinase C activation, which indicated that some A1 adenosine receptors were directly negatively coupled to adenylyl cyclase. These results suggest that adenosine can modify human cortical collecting duct functions in opposite ways according to the adenosine receptor activated.
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PMID:Role of adenosine on glucagon-induced cAMP in a human cortical collecting duct cell line. 763 60

Prostaglandin E2 (PGE2) is the major renal cyclooxygenase metabolite of arachidonic acid. Urinary excretion of PGE2 is increased by dietary salt restriction, as well in cirrhosis and congestive heart failure. To determine whether urinary PGE2 affects transport along the nephron, the actions of luminal PGE2 were studied in the isolated perfused rabbit cortical collecting duct (CCD). Luminal PGE2 transiently hyperpolarized transepithelial voltage (Vt) in a dose-dependent manner (half-maximal effect approximately 10(-8) M) in contrast to a sustained depolarization of Vt produced by basolateral PGE2. Luminal PGE2 (0.1 microM) also significantly stimulated osmotic water permeability in the CCD. In CCDs cultured on semipermeable supports, apical PGE2 stimulated adenosine 3',5'-cyclic monophosphate (cAMP) production, suggesting the effects of luminal PGE2 are mediated by adenylyl cyclase-stimulating EP2 or EP4 receptors. Sulprostone, a PGE2 analogue selective for EP1 and EP3 receptors, affected Vt only when applied from the basolateral but not the luminal surface. Luminal application of the EP2 receptor agonist butaprost was also without effect. These results suggest that luminal PGE2 affects Vt via a butaprost-insensitive EP4 receptor. The Vt effect of luminal PGE2 was not blocked by pertussis toxin, also arguing against an EP3-mediated Gi-coupled effect. Finally, 1 microM luminal PGE2 only slightly increased CCD intracellular calcium concentration ([Ca2+]i), in contrast to the marked increase in [Ca2+]i produced by basolateral PGE2 (0.1 microM).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Luminal prostaglandin E receptors regulate salt and water transport in rabbit cortical collecting duct. 765

Endothelin (ET) potently inhibits arginine vasopressin (AVP)-induced adenosine 3',5'-cyclic monophosphate (cAMP) accumulation and Na-K-adenosinetriphosphatase (Na-K-ATPase) activity in the inner medullary collecting duct (IMCD). At least two types of ET receptors exist: ETA [binds ET-1 > ET-3 = sarafotoxin S6c (S6c)] and ETB (binds ET-1 = ET-3 = S6c). We examined which of these receptors mediates biological actions of ET in freshly isolated rat IMCD cells. Binding studies revealed comparable displacement of 125I-ET-3 by ET-1, ET-3, and S6c, whereas 125I-ET-1 was displaced by ET-1 >> ET-3 = S6c. Together, these studies confirm the presence of receptors in the IMCD with ETA and ETB binding characteristics. ET-1, ET-3, and S6c were equipotent in reducing AVP-stimulated cAMP accumulation. BQ-123, at concentrations selective for ETA receptor antagonism, did not alter the effect of ET-1, ET-3, or S6c. Pertussis toxin or protein kinase C blockade, but not indomethacin, inhibited the effect of ET-1 and S6c on AVP-stimulated cAMP accumulation, consistent with activation of the same signal transduction pathways. ET-1 and S6c were equipotent in reducing forskolin-stimulated cAMP accumulation, ruling out inhibition of AVP-receptor interaction as a common mechanism of action. Finally, ET-1, ET-3, and S6c caused comparable stimulation of prostaglandin E2 (PGE2) accumulation, an effect that was not blocked by BQ-123. These data indicate that an ETB-like receptor mediates ET stimulation of PGE2 and inhibition of AVP-enhanced cAMP accumulation in the IMCD. The function of the ETA-like receptor in the IMCD remains to be determined.
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PMID:Endothelin B receptor mediates ET-1 effects on cAMP and PGE2 accumulation in rat IMCD. 769 6

Ca(2+)-activated K+ channels play an important role in Ca2+ signal transduction and may be regulated by mechanisms other than a direct effect of Ca2+. Inside-out patches of the apical membrane of confluent transformed rabbit cortical collecting duct cells cultured on collagen were subjected to patch clamp analysis. Two types of K+ channel, of medium and high conductance, were observed. The latter channel was characterized by a K+/Na+ permeability ratio of 10, an inwardly rectified current, a conductance of 80 pS at 0 mV, and an open probability dependent on both voltage and Ca2+. Guanosine 5'-triphosphate (GTP) but not a guanosine 5'-diphosphate (GDP) analogue, adenosine 5'-triphosphate (ATP), cytidine 5'-triphosphate (CTP), or inosine 5'-triphosphate (ITP), inhibited the activity of this Ca(2+)-activated K+ channel. The inhibitory effect of GTP was dose dependent, with a 50% inhibitory concentration of 10(-5) M in the absence of Mg2+. In the presence of Mg2+ (1 mM), which is required for the binding of GTP to G proteins, the 50% inhibitory concentration decreased to 3 x 10(-12) M. Pertussis toxin or cholera toxin (each at 10 ng/ml) did not prevent the inhibitory effect of GTP. After removal of GTP from the medium bathing an inhibited channel, subsequent application of Ca2+ failed to activate the channel. Ca(2+)-activated K+ channels of smooth muscle cells and proximal tubule cells did not respond to GTP. Thus, the Ca(2+)-activated K+ channel in the apical membrane of collecting duct cells is inhibited by GTP, which appears to exert its effect via a G protein that is insensitive to both cholera and pertussis toxins.
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PMID:Regulation by GTP of a Ca(2+)-activated K+ channel in the apical membrane of rabbit cortical collecting duct cells. 796 44

The immature kidney is characterized by resistance to arginine vasopressin (AVP). In the immature cortical collecting duct (iCCD), AVP-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) generation is decreased, but the mechanisms involved are not known. We examined cAMP production in isolated CCD from immature and mature rabbits. Cellular cAMP levels were measured by radioimmunoassay under basal conditions and after stimulation with hormone. Basal cAMP production in the iCCD was not different from that in the mature CCD (mCCD). In contrast, AVP- and forskolin-stimulated cAMP generation were severely decreased in the iCCD. Inhibition of endogenous prostaglandin production by indomethacin increased AVP-stimulated cAMP generation in the iCCD to levels that were not different from the mCCD. Inhibition of protein kinase C (PKC) by staurosporine and inhibition of Gi by pertussis toxin elicited a mature cAMP response in the iCCD. These data suggest that the defect in AVP-stimulated cAMP production in the iCCD is mediated by prostaglandins via 1) activation of Gi and 2) direct inhibition of the adenylyl cyclase catalytic subunit. In addition, PKC appears to play a significant role.
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PMID:Prostaglandins mediate the defect in AVP-stimulated cAMP generation in immature collecting duct. 804 63

Endothelin (ET), a powerful vasoconstrictive peptide, is distributed ubiquitously in various organs, including the vascular endothelium and tubules of the kidney. Although localized more abundantly to the glomerulus and inner medullary collecting duct, ET receptors have been identified in the proximal tubule. The possible effects of ET on proximal tubule transport and the potential role of second messengers in this process have not been described fully. To define the role of ET in proximal tubule transport, renal cortical slices were incubated for 3 min in the presence of various concentrations of ET. Incubation with low concentrations of ET-1 (1 x 10(-9) to 1 x 10(-11) M) within the physiological range stimulated both Na(+)-Pi cotransport and Na+/H+ exchange. Pretreatment with staurosporine (0.6 microM) for 25 min abolished completely the ET-induced effects on Na(+)-Pi cotransport and Na+/H+ exchange. Similarly, preincubation with phorbol ester 12-O-tetradecanoylphorbol-13-acetate (200 nM) also abolished the effects of ET on these transporters. Incubation with ET decreased significantly intracellular adenosine 3',5'-cyclic monophosphate (cAMP). Intravenous administration of pertussis toxin for 2 days prevented the ET-induced decrease in cAMP and abolished the stimulatory effects of ET on Na(+)-Pi cotransport and Na+/H+ exchange. These findings provide indirect evidence that ET participates in the regulation of proximal tubular Pi and bicarbonate homeostasis. These effects of ET are mediated by activation of protein kinase C and cAMP-dependent protein kinase A.
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PMID:Effects of endothelin on rat renal proximal tubule Na(+)-Pi cotransport and Na+/H+ exchange. 818

Prostaglandin E2 (PGE2) modulates both water and sodium transport in the rabbit cortical collecting duct (CCD). To determine whether these effects are mediated by separate PGE2 receptors, we compared the effects of PGE2 and its analogue sulprostone in the isolated perfused rabbit CCD. PGE2 increased basal water permeability (hydraulic conductivity), whereas sulprostone did not. PGE2 and sulprostone were equipotent inhibitors of water absorption when it was prestimulated by vasopressin. Pertussis toxin completely reversed the inhibitory effect of sulprostone but only partially reversed the inhibitory effect of PGE2. In contrast, a protein kinase C (PKC) inhibitor, staurosporine, partially reversed the inhibitory effect of PGE2 but had no effect on sulprostone. PGE2 also raised intracellular calcium ([Ca2+]i). This effect is coupled to its capacity to inhibit Na+ absorption. Sulprostone was 10-fold less potent than PGE2 both in raising [Ca2+]i or inhibiting sodium transport. The results suggest sulprostone selectively interacts with a PGE2 receptor coupled to pertussis toxin-sensitive inhibition of water permeability. Sulprostone less potently activates a PGE2 receptor coupled to [Ca2+]i, PKC activation, and sodium transport and completely fails to interact with the PGE2 receptor that stimulates water permeability in the collecting duct. These results suggest distinct PGE2 receptors modulate sodium and water transport in the CCD.
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PMID:Evidence that separate PGE2 receptors modulate water and sodium transport in rabbit cortical collecting duct. 823 44

Hypotonic shock (change of osmolality from 600 mosmol to 300 mosmol by lowering NaCl concentration) increases the release of organic osmolytes from isolated inner medullary collecting duct (IMCD) cells in the following sequence: taurine > betaine > sorbitol > myo-inositol > glycerophosphorylcholine (GPC). The role of G-proteins in regulating the hypotonicity-induced efflux was analysed by exposing cells to various concentrations of a G-protein inhibitor, pertussis toxin (PTX; 20-200 ng/ml), and a Gialpha-protein stimulator, mastoparan (10-50 microM). PTX diminished the hypotonic release of sorbitol and betaine by 43.2+/-9. 5% and 32.2+/-7.8% (n = 5), respectively. Efflux of GPC, myo-inositol and taurine was not significantly altered. Mastoparan (10 microM) increased osmolyte release under isotonic conditions such that release of betaine was increased 3.8-fold and that of sorbitol 2.1-fold, while GPC, myo-inositol and taurine effluxes were only slightly augmented. Under hypotonic conditions, mastoparan stimulated betaine release (1.86+/-0.2-fold, n = 5) but not that of sorbitol. As tested in connection with sorbitol and betaine release, the effect of mastoparan was abolished by PTX, but not the A23187-evoked sorbitol release. Like mastoparan, arachidonic acid increased the release of sorbitol and betaine under isotonic conditions, but under hypotonic conditions it only increased the release of betaine. As to the role of intracellular Ca2+, hypotonic shock evoked an intracellular Ca2+ peak which could be prevented by PTX. Mastoparan increased intracellular Ca2+ under isotonic conditions, whether the extracellular Ca2+ concentration was low or high. The results indicate that G-proteins are involved in regulating sorbitol and betaine efflux from IMCD cells. The G-proteins regulating sorbitol release are probably involved in generating the proper intracellular Ca2+ signal. Betaine efflux, which is independent of intracellular Ca2+, might be regulated by a G-protein-stimulated release of arachidonic acid. Thus, probably several G-proteins are involved in controlling organic osmolyte efflux from IMCD cells.
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PMID:Role of G-proteins in the regulation of organic osmolyte efflux from isolated rat renal inner medullary collecting duct cells. 901 28

In rat inner medullary collecting duct (IMCD) cells in primary culture, hypotonic stress induces Ca2+ transients consisting of an early peak phase caused by a Ca2+ release from intracellular stores and a subsequent plateau phase that involves Ca2+ entry from the extracellular milieu. In the present study, the mechanisms by which cell swelling is transduced into the Ca2+ release were investigated. The free intracellular Ca2+ concentration ([Ca2+]i) was measured using the fluorescent dye fura-2 and cell volume using a confocal laser scanning microscope. In control experiments, after reduction of extracellular osmolarity from 600 to 300 mosmol/l, by omission of sucrose, [Ca2+]i rapidly increased from 106 +/- 9 nmol/l to a peak value of 405 +/- 22 nmol/l (P </= 0.05) and thereafter reached a steady-state of 230 +/- 23 nmol/l. In low-Ca2+ conditions (10 nmol/l), the reduction of osmolarity evoked only a transient increase of [Ca2+]i by 182 +/- 11 nmol/l (P </= 0.05), which reflected Ca2+ release from intracellular stores. Hyposmotic stress had no effect on inositol 1,4,5-triphosphate (IP3) production measured by a [3H]IP3 radioreceptor assay. Preincubation with 100 micromol/l ETYA (a non-metabolisible derivative of arachidonic acid) reduced the Ca2+ response to hyposmotic stress under high and low Ca2+ conditions (87 and 85% inhibition respectively) as well as the regulatory volume decrease (RVD). Extracellular application of arachidonic acid in isotonic medium led to an increase in [Ca2+]i under high and low Ca2+ conditions. Pretreatment of IMCD cells with 50 microg/ml D609 (a phosphatidylcholine-directed phospholipase C inhibitor) or with 200 micromol/l propranolol (a phosphatidate phosphohydrolase inhibitor) reduced the hypotonic Ca2+ response more strongly than pretreatment with 5 micromol/l BPhB (a phospholipase A2 inhibitor). The Ca2+ response was also suppressed after preincubation with 200 micromol/l RHC 80267 (a diacylglycerol lipase inhibitor). Preincubation with 50 ng/ml pertussis toxin (a G-protein inhibitor) reduced the transient component of the Ca2+ response partially. We conclude that G-proteins, phosphatidylcholine-directed phospholipase C, phospholipase A2, diacylglycerol lipase and arachidonic acid, but not IP3, are involved in the mechanisms by which Ca2+ is released from the intracellular stores during RVD in IMCD cells.
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PMID:Arachidonic acid as a second messenger for hypotonicity-induced calcium transients in rat IMCD cells. 906 39


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