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)

1. Hyperinsulinaemia is considered to be a pathogenic factor for human and experimental hypertension. Thus, the contribution of the known insulin-stimulated tubular sodium reabsorption to this aetiological process has to be discussed. 2. Rats fed a fructose-enriched diet develop hyperinsulinaemia and hypertension, providing a model for studying the regulation of the tubular sodium handling and its possible relationship to hypertension. For this purpose, the sodium transport capacity of isolated nephron segments from control rats and from rats fed a fructose-enriched diet was investigated by measurement of ouabain-sensitive 86Rb uptake and of the hydrolytic activity of Na,K-ATPase. The number and affinity of insulin receptors were estimated from the specific [125I]insulin binding. 3. In rats fed a fructose-enriched diet, mild hypertension developed during the 14-day fructose diet. There were no differences, along the nephron, in basal 86Rb uptakes and ATPase activities between control rats and fructose-induced hypertensive rats. In control rats, insulin stimulated 86Rb uptake in the proximal convoluted tubule and cortical collecting duct, but exhibited an inhibitory action in the medullary thick ascending limb. In contrast, in fructose-induced hypertensive rats, 86Rb influx remained unresponsive to insulin concentrations ranging from 10(-11) to 10(-7) mol/l in the proximal convoluted tubule and cortical collecting duct. In the medullary thick ascending limb, the threshold of inhibition was displaced from 10(-11) mol/l up to 10(-7) mol/l. Insulin binding to the proximal convoluted tubule, medullary thick ascending limb and collecting duct were similar in control rats and in rats fed a fructose-enriched diet.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Insulin unresponsiveness of tubular monovalent cation transport during fructose-induced hypertension in rats. 773 97

A 30-y-old female presented with a history of hypertension and a modest degree of hyperkalemia. There was a mild degree of contraction of her ECF volume on clinical examination, with elevated levels of renin and aldosterone in plasma. No causes for secondary hypertension were found. Laboratory investigations revealed a slightly reduced glomerular filtration rate (GFR) and a subnormal kaliuretic response to exogenous mineralocorticoids. When a further degree of ECF volume contraction was induced, she was unable to conserve Na+ and Cl- appropriately. Moreover, expansion of the ECF volume led to a significant suppression of the levels of both renin and aldosterone in plasma. We speculate that these findings could be explained by a diminished net rate of reabsorption of Na+ in the cortical collecting duct. Such a reduction could lead to a diminished generation of an electrical gradient to favour the net secretion of K+ and lead to hyperkalemia with renal salt wasting. The resultant contraction of the extracellular fluid volume with the release of renin and aldosterone (and probably other vasoactive hormones) might have predisposed her to hypertension. This hypothesis was supported by the finding that NaCl supplements led to a significant drop in her blood pressure. This case could represent a new syndrome of hyperkalemia and "salt sensitive" hypertension.
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PMID:Hyperkalemia with mild ECF volume contraction: studies to provide a possible physiologic interpretation. 786 45

Since DA1 receptors regulate renal tubular sodium transport, it is possible that the reported defect in the coupling between the DA1 dopamine receptor and adenylyl cyclase (AC) in the proximal tubule (PT) is a mechanism for the increased sodium reabsorption in animal models of spontaneous hypertension. Because the distal nephron may participate in the increased sodium retention in the spontaneously hypertensive rat (SHR), we determined whether the defective DA1 receptor-AC coupling described in PT of SHR is also present in the cortical collecting duct (CCD). Radioligand binding studies with the DA1 antagonist 125I-Sch 23982 revealed similar dissociation constants and maximum receptor densities in the CCD from Wistar-Kyoto rats (WKY) and SHR. Fenoldopam, a DA1-selective agonist, stimulated AC activity to a similar extent in CCD from both rat groups. Therefore the defective DA1 receptor-AC coupling in SHR has nephron segment specificity, since it is present in PT but not in CCD. One of the AC-linked dopamine receptors is an intronless D1A cloned from brain, which is also present in PT. Because the coupling defect in the PT may reside in the third cytoplasmic loop (involved in G protein coupling), we compared the sequence of this segment of the cloned D1A receptor using genomic DNA. Because no differences were noted between WKY and SHR, the coupling defect in the PT is not due to a mutation at the third cytoplasmic loop of the D1A receptor.
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PMID:Nephron specificity of dopamine receptor-adenylyl cyclase defect in spontaneous hypertension. 809 71

Renal dopamine-1 (DA-1) receptors are involved in the regulation of sodium transport in several nephron segments, including the proximal convoluted tubule (PCT). DA-1 receptors in the PCT and cortical collecting duct of normotensive rats are linked to the stimulation of adenylyl cyclase (AC). We have reported a defect in the DA-1 receptor/AC coupling in the PCT of the spontaneously hypertensive rat (SHR) of the Okamoto-Aoki strain. Hyperactivity and hypertension are both expressed in the SHR. To determine if the DA-1 receptor coupling defect is associated with hyperactivity or hypertension, we studied the DA-1 receptor in the PCT of two new inbred rat strains derived from the SHR: the hyperactive WKHA and the hypertensive WKHT rat. Tail-cuff blood pressures taken at 4 weeks indicated that WKHT rats were not hypertensive (86 +/- 3 mm Hg, n = 6), whereas at 12 weeks systolic pressures in both SHR and WKHT rats exceeded 150 mm Hg. Hyperactivity, however, was noted in WKHA rats even at this early age. Basal AC activity was similar in WKHA and WKHT PCT in either age group. In the older rats, the DA-1 agonist fenoldopam (10(-7) mol/L) stimulated AC activity in WKHA (70.6 +/- 16.1 fmol per 3 mm PCT per 20 minutes, n = 3) but not in WKHT PCT (43.3 +/- 5.3 fmol per 3 mm PCT per 20 minutes, n = 4). Gpp(NH)p (10(-5) mol/L), a nonhydrolyzable GTP analogue, stimulated AC activity to a similar extent in WKHA and WKHT PCT.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1993 Apr
PMID:Renal dopamine-1 receptors in hypertensive inbred rat strains with and without hyperactivity. 809 3

We report the clinicopathologic, immunohistochemical, and electron microscopic study of two cases of juxtaglomerular cell tumor of the kidney with a hitherto unreported dominant papillary pattern. Both tumors were associated with high blood pressure that did not respond to medical therapy, but that returned to normal after removal of the kidney. They were well delineated, tan, and had no necrosis. The cores of the papillary structures consisted of polygonal cells found to express renin by immunohistochemistry and to contain renin protogranules by electron microscopy. The papillary fronds were covered by one layer of cuboidal epithelial cells that did not stain for renin and had ultrastructural features reminiscent of the collecting duct epithelium. These tumors must be differentiated from malignant papillary tumors of the kidney, such as papillary clear cell carcinoma, transitional cell carcinoma, and collecting duct carcinoma.
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PMID:Juxtaglomerular cell tumor of the kidney: report of two cases with a papillary pattern. 824 16

Excess 6 beta-OH-corticosterone production by family 3A cytochromes P-450 may play a role in genesis of hypertension in the spontaneously hypertensive rat (SHR), by producing a renal defect in Na+ excretion. Renal cytochromes P-450 may be a causal factor in this genetic model. Since family 3A P-450 is present in rat kidney (collecting duct), the renal family 3A catalytic (6 beta-OHase) and immunoreactive activities were compared in SHR and normotensive control (Wistar-Kyoto; WKY) rats. Corticosterone 6 beta-hydroxylation is markedly higher in SHR than in WKY renal microsomal preparations. Western blot analysis with antibodies to rat and rabbit liver family 3A isoforms demonstrated related proteins. Densitometry revealed greater relative intensity of staining in SHR compared to WKY with both antibodies. Both antibodies inhibited corticosterone 6 beta-hydroxylation by SHR renal microsomes. Increased renal 6 beta-OH-corticosterone production by increased renal family 3A cytochromes P-450 may play a role in the blood pressure elevation in SHR.
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PMID:Renal corticosterone 6 beta-hydroxylase in the spontaneously hypertensive rat. 835 46

Urodilatin is a recently described member of the atrial natriuretic peptide family, thought possibly to be synthesized in the kidney. To determine if urodilatin binding sites are present in rat and human kidney, we evaluated the effect of urodilatin on iodine-125-labeled atrial natriuretic peptide (ANP) (100 pM) binding to tissue sections using an in situ autoradiographic technique. 125I-ANP binding occurred primarily in glomeruli and medullary structures of both rat and human kidney. Increasing concentrations of urodilatin yielded a monophasic displacement of 125I-ANP binding with an IC50 of 4.2 nM, a value nearly identical to that achieved with unlabeled ANP (7.2 nM). In additional experiments, rat glomeruli and inner medullary collecting duct cells were isolated and incubated in vitro with either ANP or urodilatin (10(-11) to 10(-6) M) and cyclic guanosine-3',5'-monophosphate accumulation measured by radioimmunoassay. Dose-response curves for the two peptides were superimposable in each tissue; at 10(-6) M, ANP generated 613 +/- 41 and urodilatin 603 +/- 55 fmol cyclic guanosine monophosphate per 10 minutes per milligram protein in inner medullary collecting duct cells (p = NS). Thus, urodilatin is as effective as ANP in displacing 125I-ANP binding to both rat and human renal tissue and in generating cyclic guanosine monophosphate in renal target cells in the rat, suggesting that its physiological effects may occur through the same receptors and signaling pathways that mediate the actions of ANP.
Hypertension 1993 Apr
PMID:Urodilatin binds to and activates renal receptors for atrial natriuretic peptide. 838

Previous studies have shown that the SA gene is expressed at higher levels in the kidney of genetically hypertensive rats than in control strains and that in hybrid crosses of genetically hypertensive rats and normotensive controls, markers in or close to the SA gene cosegregate with blood pressure. The present studies examine the localization of the SA gene product in the kidney by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). cDNA was prepared from microdissected nephron segments from Sprague-Dawley (SD) rats, spontaneously hypertensive rats (SHRs), and Wistar-Kyoto (WKY) rats, and RT-PCR was performed using specific primers. In all three strains, SA gene mRNA was found to be abundantly expressed in proximal tubules. SA PCR product was occasionally detected at approximately 100-fold lower abundance in glomeruli, while no signal was obtained from the collecting duct, thick ascending limb of the loop of Henle, or arcuate artery. Within the proximal tubule of normotensive rats, distribution of SA mRNA was found to be strain dependent: in SD rats it was expressed at high levels in the proximal convoluted tubule, whereas in WKY rats it was restricted to the proximal straight tubule. In SHRs, SA PCR product was detected along the entire proximal tubule. Induction of hypertension by renal artery clamping (two-kidney, one-clamp Goldblatt model) did not alter the pattern of expression observed in the SD rat. These results indicate that an extension of SA gene expression to the full length of the proximal tubule accompanies spontaneous hypertension and that in nonhypertensive animals the pattern of gene product expression is more restricted but shows substantial strain variability.
Hypertension 1996 Mar
PMID:SA gene expression in the proximal tubule of normotensive and hypertensive rats. 861

Nitric oxide has a diuretic effect in vivo. We have shown that nitric oxide inhibits antidiuretic hormone-stimulated osmotic water permeability in the collecting duct; however, the mechanism by which this occurs is unknown. We hypothesized that inhibition of antidiuretic hormone-stimulated water permeability by nitric oxide in the collecting duct is the result of activation of cGMP-dependent protein kinase, which in turn decreases intracellular cAMP. To test this hypothesis, we microperfused cortical collecting ducts. Antidiuretic hormone-stimulated water permeability was 317 +/- 47 microm/s (P < .001). Addition of spermine NONOate, a nitric oxide donor, to the bath decreased water permeability to 74 +/- 38 microm/s (P < .002). In the presence of LY 83583, an inhibitor of soluble guanylate cyclase, spermine NONOate did not change water permeability. Addition of spermine NONOate increased cGMP production (P < .01). In the presence of the cGMP-dependent protein kinase inhibitor, spermine NONOate did not change water permeability. Since antidiuretic hormone increases water permeability by increasing cAMP, we hypothesized that nitric oxide inhibits water permeability by decreasing cAMP. In tubules pretreated with antidiuretic hormone, intracellular cAMP was 18.9 +/- 3.9 fmol/mm. In tubules treated with antidiuretic hormone and spermine NONOate, cAMP was 9.3 +/- 1.7 fmol/mm (P < .03). We also examined the effect of spermine NONOate on dibutyryl-cAMP-stimulated water permeability. In the presence of dibutyryl-cAMP, water permeability was 388 +/- 30 microm/s. Addition of spermine NONOate had no significant effect on water permeability. Time controls and inhibitors by themselves did not change antidiuretic hormone-stimulated water permeability. We concluded that nitric oxide decreases antidiuretic hormone-stimulated water permeability by increasing cGMP via soluble guanylate cyclase, activating cGMP-dependent protein kinase and decreasing cAMP.
Hypertension 1996 Mar
PMID:Mechanism of the nitric oxide-induced blockade of collecting duct water permeability. 861 24

Dahl salt-sensitive (S) rats develop hypertension in response to a high-salt diet, whereas Dahl salt-resistant (R) rats do not. There is good evidence that the Dahl S kidneys have diminished natriuretic capacity. We studied the rate of Na+ transport by primary cultures of the inner medullary collecting duct from these two strains to determine whether there were intrinsic differences. Monolayers obtained from prehypertensive S rats transported Na+ at twice the rate as monolayers from age-matched R rats. Mineralocorticoid and glucocorticoid hormones increased Na+ transport from both strains; the S rat monolayers always displayed higher transport rates than R rat monolayers with the same treatment. The Na+ entry pathway in both S and R rat monolayers was via an Na+ channel. The difference in Na+ transport was not explained by a difference in the metabolism of corticosterone, ATP content, citrate synthase activity, ultrastructural appearance, or rate of maturation. Monolayers from S rats tended to have higher protein and DNA content, but these differences could not account for the difference in Na+ transport. Anion secretion in response to adenosine 3',5'-cyclic monophosphate agonists was similar. These results demonstrate intrinsic differences in renal tubular cells that may play an important role in the pathogenesis of salt-sensitive hypertension.
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PMID:IMCD cells cultured from Dahl S rats absorb more Na+ than Dahl R rats. 894 97


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