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 investigated the effects of endothelins on receptor-mediated cyclic nucleotide metabolism in rat glomerulus, inner medullary collecting duct (IMCD), and also in cultured rat glomerular mesangial cells. Endothelin (ET)-3 dose-dependently stimulated cGMP accumulation in glomerulus, which was higher than that of ET-1 or ET-2. ETB receptor agonist IRL 1620 produced cGMP in a dose-dependent manner, mimicking the effect of ET-3. ETA receptor antagonist BQ123-Na did not inhibit ET-3- or IRL 1620-stimulated cGMP generation. NG-monomethyl-L-arginine (L-NMMA) significantly inhibited ET-3- or IRL 1620-induced cGMP production, suggesting that ET-3- or IRL 1620-stimulated cGMP generation was mediated through nitric oxide (NO). Intracellular Ca chelator BAPTA/AM and calmodulin antagonist W-7, but not Ca channel blocker nicardipine, significantly inhibited ET-3- or IRL 1620-induced cGMP generation. In cultured rat mesangial cells, ET-3 stimulated cGMP generation through NO in the presence of fetal calf serum, which was not inhibited by addition of BQ123-Na. In IMCD, ET-3 had no stimulative effect on cGMP generation. We conclude that ET-3 stimulates NO-induced cGMP generation through ETB receptor in glomerulus. This effect seems to be mediated through intracellular Ca/calmodulin, but not through Ca influx via L-type Ca channel. Mesangial cells can be a source of NO coupled to ETB receptor activation in glomerulus. From these results, mesangial ETB receptor may work to counteract the vasoconstrictive effect of endothelin caused via ETA receptor in glomerulus.
...
PMID:Endothelin (ET)-3 stimulates cyclic guanosine 3',5'-monophosphate production via ETB receptor by producing nitric oxide in isolated rat glomerulus, and in cultured rat mesangial cells. 750 43

To increase understanding of endothelin (ET) function in the kidney, we investigated binding of the radioligand of endothelin isopeptides to microdissected rat nephron segments. Specific ET-1 binding was highest in the inner medullary collecting duct, whereas the cortical and outer medullary collecting ducts showed moderate binding, as did the glomeruli. There was slight ET-1 binding to the early portion of the proximal tubule. Other nephron segments displayed little ET-1 binding. The binding profile of ET-3 along the nephron markedly resembled that of ET-1. Scatchard analyses of ET-1 and ET-3 binding to cortical collecting ducts revealed a single class of receptor for both ET-1 and ET-3. Displacement of [125I]-ET-1 binding by unlabeled ET-3 was similar to that produced by unlabeled ET-1. Moreover, a specific ETB agonist, BQ-3020, almost completely inhibited [125I]-ET-1 binding in cortical collecting ducts, whereas a specific ETA antagonist, BQ-123, had little effect. These data indicate that cortical collecting ducts express ETB receptors, to which both ET-1 and ET-3 bind equally.
...
PMID:Endothelin-1 and -3 binding to ETB receptors in rat renal tubules. 750 37

We characterized 125I-ET-1 binding to renal microvascular membranes isolated from the rat, a species showing ETB receptor-mediated renal vasoconstriction, and the rabbit in which ET-induced renal vasoconstriction is mediated by the ETA receptor. In both species, 125I-ET-1 bound in a manner consistent with a single high-affinity site. Scatchard analysis yielded Kd and Bmax values of 20.1 +/- 0.4 pM and 1343 +/- 64 fmol/mg for the rat and 21.5 +/- 0.9 pM and 810 +/- 64 fmol/mg for the rabbit. Competition binding studies with several selective (sarafotoxin 6c, BQ123) and mixed ETA/ETB (SB 209670) ET receptor ligands showed that the renal microvasculature from both species contain ETA and ETB receptors in a proportion of 40:60. In the rat, the proportion of ETA receptors was higher in the microvasculature than in glomeruli and inner medullary collecting duct cells both of which contained > 80% ETB receptors. In the rabbit, the proportion of ETA/ETB receptors was similar in the microvasculature and inner medullary collecting duct cells (approximately 40:60), whereas glomeruli contained 80% ETB receptors. Although ET-induced renal vasoconstriction in the rat and rabbit is mediated by different ET receptor subtypes, the proportion of ETA to ETB receptors is the same in the renal microvasculature from these species.
...
PMID:Characterization of 125I-endothelin-1 binding to rat and rabbit renal microvasculature. 756 73

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.
...
PMID:Endothelin B receptor mediates ET-1 effects on cAMP and PGE2 accumulation in rat IMCD. 769 6

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

In porcine kidneys we investigated the characteristics of endothelin (ET) receptors that are present in papillary tissue but not in glomeruli. Therefore, porcine inner medullary collecting duct (IMCD) cells were separated by Percoll density gradient centrifugation after enzymatic and hypotonic treatment of minced papillary tissue. Studies were performed in fresh cell suspensions and in cells in primary culture. Changes in cytosolic free Ca2+ concentration [Ca2+]i were measured by the use of fura-2. Optimum binding of ET-1 was obtained by incubation for 120 min at 37 degrees C, pH 7.0 when maximal protein content was 40 micrograms. Analysis with the LIGAND program showed an average number of binding sites (Bmax) of 26.0 +/- 30.5 fmol/mg protein and dissociation constant (Kd) of 90.5 +/- 28.6 pmol/L for ET-1 and Bmax of 246.9 fmol/mg protein and Kd of 162.5 pmol/L for ET-3. ET-1, 10(-9) to 10(-6) mol/L, dose dependently raised [Ca2+]i four to tenfold, respectively, from a mean basal level of 41 nmol/L. This rise was significantly attenuated by TMB-8 and by verapamil. Preincubation with Ni2+ almost completely prevented the increment in [Ca2+]i. ET-1 slightly suppressed basal and significantly attenuated arginine vasopressin (AVP)-induced cyclic adenosine monophosphate (cAMP) synthesis. Thus, porcine IMCD cells possess a single class of super high affinity ETB receptors (ETB1). ET-1 raises [Ca2+]i through release from intracellular stores, activation of L-type calcium channels and, probably to a larger extent, through stimulation of other channels, eg, T-type calcium channels or unselective cation channels.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Characteristics of endothelin receptors and intracellular signalling in porcine inner medullary collecting duct cells. 839 2

The existence of endothelin (ET) receptor subtypes has recently been implicated in the different biological effects of ET in various tissues. Indeed, the cDNAs for two types of ET receptors, ETA and ETB, have been cloned. To further gain insights into ET function in the kidney we examined 125I-labeled ET-1 and ET-3 binding to microdissected rat nephron segments. Specific ET-1 binding was highest in the inner medullary collecting duct, whereas the cortical and outer medullary collecting ducts as well as glomeruli showed moderate binding. There was low, although not significant, ET-1 binding to the early portion of the proximal tubule. Other nephron segments displayed little ET-1 binding. The binding profile of ET-3 along the nephron markedly resembled that of ET-1. Scatchard analyses of binding of ET-1 and ET-3 using cortical collecting ducts revealed a single class of receptor for both ET-1 and ET-3; apparent dissociation constants were 2.05 +/- 0.72 and 2.58 +/- 0.32 nM, and maximal binding capacity values were 0.408 +/- 0.058 and 0.511 +/- 0.047 fmol/mm, respectively. Displacement of 125I-ET-1 binding by unlabeled ET-3 was similar to that produced by unlabeled ET-1. Furthermore, a specific ETB agonist, BQ 3020, almost completely inhibited 125I-ET-1 binding in cortical collecting ducts, whereas a specific ETA antagonist, BQ 123, had little effect. These data indicate that cortical collecting ducts express ETB receptors, to which both ET-1 and ET-3 bind equally.
...
PMID:Endothelin-1 and endothelin-3 binding to rat nephrons. 849 35

Rats with experimental liver cirrhosis have increased endothelin-1 (ET-1) plasma concentrations and show a tendency toward sodium and water retention. We therefore analyzed the renal ET system in cirrhotic rats and control rats, as the renal ET system is involved in the regulation of water and sodium excretion. Cirrhosis was induced by carbon tetrachloride (CCl4) administration. We analyzed the expression of ET receptor subtypes in the renal cortex and medulla using Scatchard analysis and receptor autoradiography, and measured plasma and renal tissue ET-1 concentrations using a specific radioimmunoassay. Furthermore, we analyzed the effects of the nonselective (A/B) ET receptor antagonist bosentan on water and sodium excretion and glomerular filtration rate. Our study revealed an overexpression of the ETB receptor in the renal medulla of rats with liver cirrhosis, whereas the density of ETB receptor in the cortex and the ETA receptor in the cortex and medulla were similar in both cirrhotic and control rats. Receptor autoradiography showed that the upregulation of medullary ETB in cirrhotic rats was due to an upregulation of ETB in the inner medullary collecting duct cells. The highest ET-1 concentrations were observed in the renal medulla of cirrhotic rats. Glomerular filtration rate decreased in cirrhotic rats but was not altered after bosentan treatment in cirrhotic and control rats. Bosentan decreased sodium excretion in both cirrhotic and control rats to a similar extent, whereas water excretion was reduced by bosentan only in cirrhotic rats. We therefore suggest that the upregulation of medullary ETB in cirrhotic rats is involved int he regulation of water excretion in rats with CCl4-induced cirrhosis.
...
PMID:Renal endothelin system in rats with liver cirrhosis. 858 36

Previous experiments have shown that epithelial cells in the renal medulla produce endothelin-1 (ET-1) and possess ETB receptors. It has been suggested that medullary ET-1 may affect water and sodium absorption along the collecting ducts in an autocrine fashion. To study possible mechanisms responsible for the regulation of medullary ET-1 production, experiments were performed in M-1 cells and mIMCD-K2 cells, cell lines derived from cortical and inner medullary collecting ducts of SV40 transgenic mice, grown to confluence on collagen-coated filter inserts. Both cell lines were found to express ET-1 mRNA and to secrete ET almost exclusively into the basolateral medium as long as the transepithelial resistance was high. Inhibition of transcription with actinomycin D was followed by a decline in both ET mRNA [halftime (t1/2) = 30 min] and ET secretion (t1/2 = approximately 90 min). The addition of arginine vasopressin (AVP, 10(-8) M; 2- or 4-h exposure) or incubation of M-1 cells in hypertonic media (+50 mM NaCl, 4- or 6-h exposure) did not significantly alter ET secretion or ET-1 mRNA expression. In contrast, simultaneously increasing AVP(10(-8) M in the basolateral medium) and tonicity (+50 mM NaCl) for 4 h increased ET secretion (from 28.9 +/- 3.9 to 41.8 +/- 3.8 pg.h-1.mg protein-1; P = 0.029, n = 10) and ET-1 mRNA (control = 2,138 cpm/microliter, log of 3.33 +/- 0.048, n = 4; AVP + NaCl = 3,548.1 cpm/microliter, log of 3.55 +/- 0.09; P = 0.045, n = 5). Exposure of M-1 cells to hypertonic media (+50 mM NaCl or 100 mM mannitol) for 24 h was associated with a marked reduction of ET secretion (-83.9% with NaCl and -78.4% with mannitol; P < 0.0001). This reduction was attenuated, but not prevented, by the presence of AVP in the basolateral medium (-40%). ET-1 mRNA, in contrast, did not change with 24-h exposure to hypertonic media and increased when AVP was present. Results are compatible with the concept that generation of ET by collecting duct cells may contribute in a complex and time-dependent fashion to the paracrine control of collecting duct cell function.
...
PMID:Synthesis and secretion of endothelin in a cortical collecting duct cell line. 877 Jan 64

The cellular localization of endothelin receptors in the inner medulla of the rat kidney was investigated by using high resolution light and electron microscopic autoradiography, with the microwave irradiation fixation methods. Kidney slices were incubated with 125I-endothelin-1 alone or with selective ligands for the endothelin ETB and/or ETA receptors for light microscopic autoradiography. At the microscopic level, 125I-endothelin-1 was found to bind specifically to the glomeruli, arterioles and peritubular spaces in the cortex and vasa recta and surrounding tissues in the inner medulla. These bindings were also observed when the tissue slices were incubated in the presence of IRL1620 (ETB receptor agonist) or 97-139 (ETA receptor antagonist). Electron microscopic autoradiography using 125I-endothelin-1 in the inner medulla revealed silver grains over endothelial cells of the vasa recta and interstitial and collecting duct cells. No grains were detected over inner lining cells of the thin limbs of Henle's loop. These interstitial cells contained abundant microorganelles and lipid droplets, and had extensive cytoplasmic processes that closely related to the basement membranes of the vasa recta and loop of Henle. These findings demonstrate that type 1 interstitial cells are also primary sites for endothelin receptors as well as endothelial cells of the vasa recta and collecting duct cells in the inner medulla.
...
PMID:High resolution localization of endothelin receptors in rat renal medulla. 880 82


1 2 3 Next >>

---