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)

The diverse biological actions of endothelins (ET) appear to be mediated by specific cell-surface receptors. Autoradiography and membrane binding studies have shown abundant ET binding sites in the kidney. However, their expression in specific types of renal cells is unclear. We studied the binding of 125I-labelled endothelin-1 in freshly isolated cell suspensions from canine inner medullary collecting duct. Competition binding experiments revealed the presence of specific high-affinity binding sites: unlabelled ET-1 and ET-2 compared with the radioligand with an IC50 of 135 and 83 pM, respectively, while the IC50 of ET-3 and big ET-1 were 2 and 4 orders of magnitude higher, indicating the presence of ETA-type receptor. Angiotensin II, vasopressin, and atrial natriuretic peptide (ANP) did not compete for ET binding even at a concentration of 10(-6) M. Saturation binding experiments showed a single class of binding sites of high density (Bmax = 56.7 +/- 10.3 fmol/10(6) cells) and high affinity (Kd = 69.8 +/- 10 pM). In contrast, ANP receptors in the same cell preparations appeared as two classes of binding sites with widely different affinity and density. The high-affinity ANP site (Kd = 311 +/- 48 pM) was compatible with ANP-B (guanylate cyclase-coupled) receptor. ET-1 did not compete for this receptor. ET-1 (10(-7) M) did not alter ANP-induced cGMP generation in these cells (3.8-fold increase at 10(-7) M ANP), nor basal levels of cGMP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Specific endothelin binding sites in renal medullary collecting duct cells: lack of interaction with ANP binding and cGMP signalling. 128 83

Endothelins may be important regulators of renal inner medullary collecting duct (IMCD) function. These peptides are secreted in large amounts by IMCD cells and can, in turn, potently inhibit sodium and water transport systems in the IMCD. This study characterized endothelin (ET) receptors in the IMCD in order to gain insight into this unique renal autocrine system. Radioligand binding studies with 125I-ET-1 yielded a B(max) of 205.7 fmol/mg and a KD of 218 pM for ET-1. Similar studies with 125I-ET-3 yielded two populations of receptors for ET-3, one with a KD of 50 pM and one with a KD of 920 pM. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of IMCD cells covalently labeling with 125I-ET-1 yielded two bands, one at 97 kDa with affinities of ET-1 greater than ET-2 much greater than ET-3 and one at 47 kDa with affinities ET-1 greater than or equal to ET-2 = ET-3. Reverse transcription and polymerase chain reaction revealed the presence of both endothelin receptor types A and B. These data indicate that IMCD cells have high affinity, high density receptors for endothelin and express both known types of endothelin receptor.
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PMID:Characterization of endothelin receptors in the inner medullary collecting duct of the rat. 131 15

Recent studies have revealed that endothelins (ETs) have at least two types of receptors. One receptor has high affinity to ET-1 and ET-2 and low affinity to ET-3 (A type). The other receptor binds almost equally to ET-1, ET-2, and ET-3 (B type). In this study, microlocalization of mRNA coding for the A-type and B-type ET receptors was carried out in the rat kidney using a reverse transcription and polymerase chain reaction assay of individual microdissected renal tubule segments along the nephron, glomeruli, vasa recta bundle, and arcuate arteries. Large signals for the B-type receptor polymerase chain reaction product were detected in the initial and terminal inner medullary collecting duct and the glomerulus, while small signals were found in the cortical collecting duct and outer medullary collecting duct, vasa recta bundle, and arcuate artery. In contrast, A-type receptor mRNA was detected only in the glomerulus, vasa recta bundle, and arcuate artery. Thus, the two ET receptor subtypes are distributed differently along the nephron. This suggests that the two types of receptors and ET families may affect kidney functioning in different ways.
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PMID:Different localization of two types of endothelin receptor mRNA in microdissected rat nephron segments using reverse transcription and polymerase chain reaction assay. 132 37

Experiments were performed in anesthetized rats to examine the possibility that endothelin (ET) modifies renal epithelial function in addition to its well-established hemodynamic actions. Infusion of ET-3 at rates between 34 and 178 ng.kg-1.min-1 was in many cases followed by a rise in urine flow and a persistent decrease in urine osmolality, whereas glomerular filtration rate (GFR) did not significantly change. The extent of ET-induced diuresis was dependent on the response of GFR: in rats in which ET-3 infusion caused a marked reduction of GFR (greater than 70%) ET-induced diuresis was not seen, even though urine osmolality still fell significantly. From animal to animal, ET-induced changes of urine flow or GFR did not correlate significantly with the rate of ET-3 infusion. ET-1, another ET isopeptide, also produced water diuresis when administered in GFR-neutral doses. Urinary excretion of total solutes and of sodium was not significantly altered by ET-3. Infusion of vasopressin blunted the diuretic effect of ET-3, whereas ET-3-induced water diuresis was not measurably altered by chronic or acute treatment with a converting enzyme inhibitor or by acute inhibition of prostaglandin synthesis. Induction of water diuresis was not secondary to an inhibition of vasopressin secretion since it could be demonstrated in homozygous Brattleboro rats in which antidiuresis was produced by the infusion of vasopressin at a rate of 200 microU.kg-1.min-1. These data suggest that ET may be an inhibitory modulator of the hydrosmotic action of vasopressin at the level of the renal collecting duct.
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PMID:Induction of water diuresis by endothelin in rats. 141 80

Endothelins regulate nephron sodium and water transport, prostaglandin E2 (PGE2) synthesis, and phospholipid metabolism. Recent studies suggest that renal tubule cells synthesize endothelins. To determine which nephron sites have such potential, endothelin production by cells derived from different nephron segments was examined. Immunoreactive endothelin 1 (ET-1) and endothelin 3 (ET-3) were measured in supernatants of cultured rabbit proximal tubule (PT), medullary thick ascending limb (MTAL), cortical collecting tubule (CCT), and inner medullary collecting duct (IMCD) cells. All cell types released immunoreactive ET-1 and ET-3. However, the amounts of endothelin produced differed as follows: IMCD greater than MTAL greater than CCT much greater than PT for ET-1 and IMCD greater than MTAL = PT = CCT for ET-3; in all cases ET-1 much greater than ET-3. To confirm de novo ET-3 synthesis, IMCD cells were labeled with [35S]cysteine, and the supernatant was immunoprecipitated with anti-ET-3 antibody. Sample and standard ET-3 eluted at identical positions on high-performance liquid chromatographs, confirming de novo synthesis of ET-3 by cultured IMCD cells. These data raise the possibility of an important functional role for nephron-derived endothelin and, in particular, endothelin produced by tubule cells in the medulla.
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PMID:Endothelin synthesis by rabbit renal tubule cells. 187 47

The distribution of endothelin-like immunoreactivity was examined in normal rat kidneys using the immunoperoxidase technique. A specific polyclonal antibody to endothelin 1, which recognized endothelin 1 and its precursor molecule, big endothelin, was raised in rabbits. Immunoperoxidase staining revealed specific endothelin-like immunoreactivity in the renal cortex, medulla, and papilla. Immunostaining density was greatest in the renal papilla where staining was predominantly localized to the vasa rectae of the distal nephron segments. Cytoplasmic immunostaining was noted focally in collecting duct cells in the renal papilla. In the renal medulla, intense immunostaining was identified in the vasa rectae. Cortical immunostaining was localized to the endothelial surfaces of arcuate arteries, veins, arterioles and peritubular capillaries. Glomerular immunostaining followed a capillary loop distribution and appeared to be predominantly localized to endothelial cells with smaller amounts of reaction product overlying the mesangium. The most proximal portion of the proximal tubule brush border and papillary collecting duct epithelium demonstrated focal endothelin-like immunostaining. We conclude that endothelin-like immunoreactivity is widely distributed in renal tissue compatible with important autacrine and paracrine actions in the kidneys.
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PMID:Localization of endothelin-like immunoreactivity in rat kidneys. 205 11

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.
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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.
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PMID:Endothelin-1 and -3 binding to ETB receptors in rat renal tubules. 750 37

Endothelins (ET) possess both vasodilatory and vasoconstrictive properties. The renal actions of ET-1 and ET-3, as well as in vivo interactions of these two isopeptides with the prostaglandin and endothelium-derived relaxation factor/nitric oxide systems were studied in anesthetized dogs. The ETs were infused intrarenally at doses not affecting systemic hemodynamics. Both ET-1 and ET-3 induced an early transient renal vasodilation, followed by a prolonged vasoconstriction. Inhibition of nitric oxide synthase with NG-monomethyl-L-arginine completely abolished the renal vasodilation induced by either ET-1 or ET-3 and enhanced the vasoconstriction. Endothelin-1 was associated with an increase in the renal release of prostacyclin, while urinary thromboxane A2 was increased after ET-3 administration. Inhibition of cyclooxygenase (with indomethacin) augmented the renal vasoconstriction induced by ET-1, but inhibition of cyclooxygenase (with meclofenamate) abolished the ET-3-evoked vasoconstriction. Endothelin-1 showed little effects on urinary water and sodium excretion; however, ET-3 displayed significant diuretic and natriuretic effects, which were inhibited by nitric oxide synthase inhibition. These findings suggest that these two isopeptides activate the endothelial endothelium-derived relaxation factor/nitric oxide system, which elicits early renal vasodilation, whereas direct effects on the vascular smooth muscle leads to vasoconstriction. Endothelin-3 causes diuresis and natriuresis, possibly by inducing release of nitric oxide in medullary collecting duct cells.
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PMID:Renal actions of endothelin-1 and endothelin-3: interactions with the prostaglandin system and nitric oxide. 754 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.
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PMID:Characterization of 125I-endothelin-1 binding to rat and rabbit renal microvasculature. 756 73


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