Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The bulk of studies of the actions of atrial natriuretic peptides (ANP) have focussed on the carboxyterminal derivative (ANP 99-126) of the prohormone (ANP 1-126), but recent evidence indicates that an additional peptide derived from ANP 1-126, namely, ANP 31-67 also circulates, and has natriuretic actions. 2. The effects of ANP 31-67 on inner medullary collecting duct (IMCD) Na+ transport have been examined in freshly prepared suspensions of rabbit IMCD cells. Like ANP 99-126, ANP 31-67 reduces Na+ transport in these cells. 3. However, unlike ANP 99-126, this effect is not mediated by cGMP, and does not result from inhibition of apical Na+ channels. Rather, ANP 31-67 inhibits basolateral Na/K-ATPase, probably via the stimulation of PGE2 synthesis. 4. These results are discussed in the context of other natriuretic substances (interleukin 1 and endothelin), which also inhibit Na+ reabsorption by PGE2-mediated inhibition of Na/K-ATPase.
 ...
PMID:Regulation of collecting duct Na+ reabsorption by ANP 31-67. 762 4

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)
 ...
PMID:Luminal prostaglandin E receptors regulate salt and water transport in rabbit cortical collecting duct. 765

With established urinary markers of kidney integrity the early renal effects of lead have previously been considered to be mainly tubular or tubulointerstitial. In a cross-sectional study on 81 male lead-exposed workers and 45 age-matched controls (median blood lead concentrations 2.03 and 0.34 mumol/l respectively) not only well-established but also new urinary markers of renal integrity preferentially or exclusively located along the different nephron segments were analysed. Markers related to the glomerulus were 6-keto-prostaglandin 1 alpha, thromboxane B2, mainly produced in the glomerulus, and the extracellular matrix protein fibronectin. Markers of the proximal tubule were the brush-border antigens BBA, BB50, and HF5 and the intestinal alkaline phosphatase. Prostaglandin E2 and F2 alpha, preferentially synthesized in the collecting duct and medullary interstitial cells, served as markers of these more distal nephron segments. In contrast to previous studies on the early phase of lead nephrotoxicity, not only tubular but also glomerular involvement could be shown in the study presented here by increases in the median values of 6-keto-prostaglandin 1 alpha and decreases in fibronectin. The proximal tubular markers intestinal alkaline phosphatase and BBA confirmed that this particular segment of the nephron is affected by lead. Effects on the collecting tubule or medullary interstitial cells could also be observed. It is concluded that lead affects both the glomerulus and the tubular apparatus and that combinations of new and established markers could be valuable for a better definition and early detection of lead nephropathy.
 ...
PMID:Nephron target sites in chronic exposure to lead. 770 57

Endothelins (ET) and prostaglandin E2 are synthesized in the inner medulla by collecting duct epithelium and interstitial cells, respectively. All ascending vasa recta (AVR) blood returns from the inner medulla to the cortex in outer medullary vascular bundles. We reasoned that hormones might influence medullary blood flow by diffusing across AVR fenestrations to modulate vasoconstriction of outer medullary descending vasa recta (OMDVR). To investigate this possibility, OMDVR dissected from vascular bundles were exposed to ET-1, 2, or 3. Each endothelin isoform induced stable vasoconstriction with potency, ET-1 > ET-2 > ET-3 (EC50, 1.8 x 10(-15), 5.9 x 10(-12), and 8.8 x 10(-10) M, respectively). The ETA receptor antagonist BQ-123 and BQ-610 (10(-6) M), as well as an ETA and ETB receptor antagonist combination, attenuated vasoconstriction due to ET-1 (10(-12) M). BQ-123 had no effect on the response to ET-3 (10(-8) M). The ETB receptor antagonist BQ-788 (10(-6) M) attenuated the response to ET-3 (10(-10) M), but not that to ET-1 (10(-12) M). Finally, PGE2 (10(-6) M) reversibly dilated OMDVR preconstricted with ET-1 (10(-12) M) or ET-3 (10(-8) M) but not ET-1 (10(-10) M). We conclude that ET-1,2, and 3 are potent constrictors of OMDVR and the response to ET-1 is mainly ETA receptor subtype mediated, while ET-3 acts via the ETB. PGE2 modulates ET induced constriction. These findings are consistent with interactive feedback and control of medullary perfusion by locally synthesized hormones.
 ...
PMID:Prostaglandin E2 abrogates endothelin-induced vasoconstriction in renal outer medullary descending vasa recta of the rat. 776 13

The effect of insulin on water and urea transport was examined in normal isolated rat inner medullary collecting duct (IMCD). Hydraulic conductivity (Lp, x 10(-6) cm.atm-1.s-1), diffusional water permeability (Pdw, x 10(-5) cm/s) and [14C]urea permeability (x 10(-5) cm/s) were studied at 37 degrees C and pH 7.4. Insulin (6 x 10(-8) M; 200 microU/ml) added to the bath fluid enhanced Lp from 0.40 +/- 0.10 to 1.21 +/- 1.40 (P < 0.01) and Pdw from 42.40 +/- 3.40 to 58.50 +/- 5.00 (P < 0.02) and also stimulated Lp in a dose-dependent manner. In the presence of antidiuretic hormone (ADH)-stimulated Pdw (10 microU/ml), insulin increased Pdw even more. Prostaglandin E2 (10(-5) M) added to the bath reversibly increased insulin-induced Lp. Forskolin (10(-4) M) blocked the action of insulin. Colchicine (10(-4) M) and V1-receptor antagonist (10(-4) M) inhibited the development but not the maintenance of insulin-stimulated Pdw. Vanadate (2.5 x 10(-6) M) enhanced Pdw. Polymyxin B (10(-5) M) inhibited the insulin-stimulated Pdw, whereas in a glucose-free medium insulin did not enhance Pdw. Urea transport was not affected by insulin. These data suggest that insulin may enhance water transport, probably by stimulating glucose transporters, which would serve as a water channel. We cannot rule out the possibility that insulin may be eliciting existing ADH-like mechanisms of water transport, beyond the microtubule step, to establish water transport.
 ...
PMID:Effect of insulin on water and urea transport in the inner medullary collecting duct. 816 Jul 87

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.
 ...
PMID:Evidence that separate PGE2 receptors modulate water and sodium transport in rabbit cortical collecting duct. 823 44

The physiological effects of PGE2 appear to be mediated by at least three different "E-prostanoid" receptors designated EP1,EP2, and EP3. These receptors are differentially activated by structural PGE analogs (such as misoprostol) and each couples to a different signal transduction mechanism. Studies demonstrating that inhibition of water absorption in the collecting duct is mediated by a Gi coupled mechanism, suggests that an EP3 receptor is involved the renal effects of PGE2. We used in situ hybridization to determine the tissue distribution of the rabbit EP3 receptor. [alpha-35S] UTP labeled antisense RNA, comprising transmembrane domains IV through VII, was hybridized to tissue sections. Specific labeling of kidney, stomach and adrenal was observed. In the kidney, medullary thick ascending limb and cortical and medullary collecting ducts were intensely labeled, while no labeling of glomeruli, proximal tubules, or cortical thick ascending limbs was observed. The adrenal gland labeled exclusively in the medulla. In the stomach the gastric epithelial crypts were the predominant site of hybridization, without evidence of labeling of the smooth muscle. These results suggest an important role for the EP3 receptor in mediating PGE2 effects in these tissues.
 ...
PMID:In situ hybridization and localization of mRNA for the rabbit prostaglandin EP3 receptor. 830 38

The inner medullary collecting duct (IMCD) is the final arbiter of renal Na+ excretion, and Na+ transport in this segment is controlled by a wide variety of hormones and renal autacoids. This review examines the mechanisms of IMCD Na+ transport and its regulation using results obtained from micropuncture and microcatheterization studies in the intact animal, as well as data from isolated perfused tubules, freshly prepared cell suspensions, and cultured IMCD cells. Where appropriate, results from closely related tissues such as the cortical collecting duct and model urinary epithelia are examined. Na+ reabsorption in this segment occurs predominantly via apical amiloride-sensitive Na+ channels and basolateral Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase). Although there is some evidence for the activities of other transporters such as Na(+)-K(+)-2Cl- and Na-Cl cotransporters and Na+/H+ exchanger, their role in Na+ homeostasis remains undefined. Mineralocorticoids augment the activities of both apical Na+ channels and basolateral Na(+)-K(+)-ATPase by a variety of complex mechanisms. Prostaglandin E2 inhibits Na(+)-K(+)-ATPase and appears to mediate the actions of several peptide hormones, including endothelin, interleukin-1, and atrial natriuretic peptide [ANP-(31-67)]. Several peptides in the ANP family [ANP-(99-126), urodilatin, and brain natriuretic peptide] bind to guanylate cyclase-linked receptors, leading to inhibition of apical Na+ channel function. These mechanisms of regulation of IMCD Na+ transport likely play important roles in total body Na+ balance in health and disease.
 ...
PMID:Hormonal regulation of inner medullary collecting duct sodium transport. 836 30

We recently reported a novel intracellular mechanism of renal Na-K-ATPase regulation by agents that increase cell cAMP, which involves protein kinase A-phospholipase A2 and is mediated by one or more arachidonic acid metabolites (Satoh, T., H. T. Cohen, and A. I. Katz. 1992. J. Clin. Invest. 89:1496). The present studies were, therefore, designed to assess the role of eicosanoids in the modulation of Na-K-ATPase activity in the rat cortical collecting duct. The effect of various cAMP agonists (dopamine, fenoldopam, vasopressin, forskolin, and dibutyryl cAMP), which inhibited the pump to a similar extent (approximately 50%), was independent of altered Na entry as it was elicited in the presence of amiloride or nystatin, or when NaCl was replaced with choline Cl. This effect was completely blocked by SKF 525A or ethoxyresorufin, two inhibitors of the cytochrome P450-dependent monooxygenase pathway, or by pretreating the animals with CoCl2, which depletes cytochrome P450. Equimolar concentrations (10(-7) M) of the cyclooxygenase inhibitors indomethacin or meclofenamate caused only a partial inhibition of the cAMP agonists' effect on the pump, whereas nordihydroguaiaretic acid or A 63162, two inhibitors of the lipoxygenase pathway, were without effect. Furthermore, two products of this pathway, leukotriene B4 and leukotriene D4, had no effect on Na-K-ATPase activity, and ICI 198615, a leukotriene receptor antagonist, did not alter pump inhibition by cAMP agonists. Several P450 monoxygenase arachidonic acid metabolites (5,6-epoxyeicosatrienoic acid; 11,12-epoxyeicosatrienoic acid; 11,12-dihydroxyeicosatrienoic acid; and 12(R)-hydroxyeicosatetraenoic acid) as well as PGE2 inhibited the Na:K pump in dose-dependent manner, but the effect of PGE2 was blocked when Na availability was altered, whereas that of 12(R)-HETE remained unchanged. We conclude that the cytochrome P450-monooxygenase pathway of the arachidonic acid cascade plays a major role in the modulation of Na:K pump activity by eicosanoids in the rat cortical collecting duct, and that products of the cyclooxygenase pathway may contribute to pump inhibition indirectly, by decreasing intracellular Na.
 ...
PMID:Intracellular signaling in the regulation of renal Na-K-ATPase. II. Role of eicosanoids. 838 20

In a previous study we have reported the existence of alpha2- and beta-adrenoceptors in cultured rat inner medullary collecting duct (IMCD) cells. In this report, we examined the effect of epinephrine on intracellular adenosine 3',5'-cyclic monophosphate (cAMP) accumulation and evaluated whether alpha2-adrenoceptors interact with beta-receptors, vasopressin receptors, and prostaglandin (PG) E2 receptors by measuring cAMP generation. Epinephrine stimulated cAMP accumulation in a dose-dependent manner [half-maximal effective concentration (EC50) = 300 nM]. Rauwolscine (10 microM) enhanced epinephrine effects, shifting the dose-response curve for epinephrine to the left (EC50 = 120 nM); however, beta-antagonists inhibited epinephrine-induced cAMP accumulation. Epinephrine (10 microM) inhibited cAMP accumulation maximally induced by isoproterenol (10 microM); this effect was reversed by rauwolscine (10 microM). Epinephrine inhibited vasopressin (100 nM)-induced cAMP accumulation but failed to inhibit PGE2 (10 microM)-induced cAMP accumulation. We conclude that epinephrine acts as an alpha2- and beta-adrenoceptor agonist and that alpha2-adrenoceptors interact with beta-adrenoceptors and vasopressin receptors but not with PGE2 receptors on cAMP accumulation. This suggests that alpha2-adrenoceptors play a physiological role via interaction with different hormone receptors.
 ...
PMID:Effect of epinephrine on cAMP accumulation in cultured rat inner medullary collecting duct cells. 912 95


<< Previous 1 2 3 4 5 6 7 8 Next >>