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 localization of mRNA for atrial natriuretic peptide (ANP) receptor subtypes (A, B, C) in the kidney was examined. Quantitative analysis of the ribonuclease protection assay showed that the numbers of type A receptor (ANPRA) mRNA were 6.9 x 10(7) in the glomeruli and 10.4 x 10(7) molecules/micrograms of total RNA in the inner medulla, and that of type C receptor (ANPRC) mRNA was 21.7 x 10(7) molecules/micrograms of total RNA in the glomeruli. The type B receptor (ANPRB) mRNA was present in smaller numbers (4.5-4.9 x 10(6) molecules/micrograms of total RNA) evenly throughout the kidney fractions. In situ hybridization demonstrated both ANPRA and ANPRC mRNA selectively in the glomerular epithelial cells and ANPRA mRNA in the collecting duct cells of the inner medulla. ANPRC was also localized on the foot processes of glomerular epithelial cells by immunohistochemistry using a specific antibody against the receptor. These results indicate that ANPRA is the major biologically active receptor for the ANP family of hormones in the kidney and is present selectively on the glomerular epithelial cells and inner medullary collecting duct cells. These cells are presumed to play a role in the regulation of glomerular filtration rate and sodium excretion induced by the family of ANP.
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PMID:Expression of mRNA for natriuretic peptide receptor subtypes in bovine kidney. 806 92

The aim of the present study was to analyze the expression of natriuretic peptide receptors in human collecting duct, by using a newly established SV40 cell line (HCD). ANP and C-type natriuretic peptide (CNP) induced a concentration-dependent increase in cGMP suggesting the presence of type-A (NPR-A) and type-B (NPR-B) receptors, respectively. Threshold concentrations were 1 pM and 1 nM, respectively, and stimulated over basal cGMP ratios were 500 and 160 at 0.1 microM ANP and CNP. The urodilatin concentration-response curve was similar to that of ANP. [125I]-ANP bound specifically to HCD cells in a time-dependent fashion, reaching a plateau-phase between one and two hours at 4 degrees C. Equilibrium saturation binding curves suggested a single group of receptor sites (Kd = 421 +/- 55 pM, Bmax = 49.2 +/- 8.8 fmol/mg protein, Hill coefficient = 1.44 +/- 0.1, N = 6). Binding of [125I]-ANP was not displaced by CNP or by C-ANP (4-23), a specific ligand of clearance receptors (NPR-C), and thus occurred mainly via NPR-A. Neither Northern blot analysis nor RT-PCR could detect NPR-C mRNA, although the latter was clearly identified in control human glomerular visceral epithelial cells. In contrast, PCR products with the expected lengths were obtained for NPR-A and NPR-B. In conclusion, HCD cells express both NPR-A and NPR-B, as demonstrated by mRNA and cGMP production studies, but fail to produce NPR-C. This suggests that the human cortical collecting duct is a target for ANP, CNP and urodilatin.
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PMID:Receptors for natriuretic peptides in a human cortical collecting duct cell line. 899 44

Natriuretic peptides (NP) constitute hormonal systems of great clinical impact. This report deals with Urodilatin (URO), a renal natriuretic peptide type A. From the gene of NP type A, a message for the preprohormone is transcribed in heart and kidney. The cardiac prohormone CDD/ANP-1-126 is synthesized in the heart atrium and processed during exocytosis forming the circulating hormone CDD/ANP-99-126. URO (CDD/ANP 95-126) is a product from the same gene, but differentially processed in the kidney and detected only in urine. Physiologically, URO acts in a paracrine fashion. After release from distal tubular kidney cells into the tubular lumen, URO binds to luminal receptors (NPR-A) in the collecting duct resulting in a cGMP-dependent signal transduction. cGMP generation is followed by an interaction with the amiloriode-sensitive sodium channel which induces diuresis and natriuresis. In this way, URO physiologically regulates fluid balance and sodium homeostasis. Moreover, URO excretion and natriuresis are in turn dependent on several physiological states, such as directly by sodium homeostasis. Pharmacologically, URO at low dose administered intravenously shows a strong diuretic and natriuretic effect and a low hypotensive effect. Renal, pulmonary, and cardiovascular effects evoked by pharmacological doses indicate that URO is a putative drug for several related diseases. Clinical trials show promising results for various clinical indications. However, the reduction in hemodialysis/hemofiltration in patients suffering from ARF following heart and liver transplantation, derived from preliminary trials recruiting a small number of patients, was not confirmed by a multicenter phase II study. In contrast, data for the prophylactic use of URO in this clinical setting suggest a better outcome for the patients. Furthermore, treatment of asthmatic patients showed a convincingly beneficial effect of URO on pulmonary function. Patients with congestive heart failure may also profit from URO treatment, as it increases stroke volume and PCWP. Moreover, preliminary results from recent studies indicate that URO may also be effective in patients suffering from hepato-renal syndrome.
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PMID:Urodilatin, a natriuretic peptide with clinical implications. 951 77

Vasopressin plays a primary role in the concentration of urine to maintain body fluid homeostasis. The collecting duct as well as thick ascending limb is a major target site of vasopressin. The antidiuretic action of vasopressin is mediated by the V2 receptor in the basolateral membrane of principal cells in the collecting ducts. The binding of vasopressin to V2 receptors causes an activation of adenylate cyclase and a synthesis of cAMP. Vasopressin regulates water and ion transport through V2 receptor-mediated ion channels and transporters. In contrast, the V1a receptor mainly in the luminal membrane of distal nephron regulates basolateral V2 receptor-mediated action with regard to water and ion transport through the activation of G(q/11) and phosphoinositide turnover. Guanylate cyclase forms three types of ANP receptors, although NPR-A and B (GC-A and B) are biologically active and related to the synthesis of cGMP. Urodilatin, synthesized by the kidney, causes natriuresis by binding to GC-A in the collecting ducts. ANP causes diuresis and natriuresis, at least in part by inhibiting the V2 receptor-mediated action of AVP in the collecting ducts. The site of interaction of ANP and AVP is post cAMP synthesis, at least in the collecting ducts. The roles of AVP and ANP under pathophysiological conditions have been reported.
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PMID:Physiological effects of vasopressin and atrial natriuretic peptide in the collecting duct. 1147 37

Previously, we showed that increased extracellular tonicity promotes increased type A natriuretic peptide receptor (NPR-A) expression through a p38 MAPKbeta pathway in inner medullary collecting duct cells. The endothelial and inducible nitric-oxide synthase (eNOS and iNOS respectively) genes are also expressed in this nephron segment and are thought to play a role in regulating urinary sodium concentration. We sought to determine whether changes in tonicity might regulate NOS gene expression, and if so, whether these latter changes might be linked mechanistically to the increase in NPR-A gene expression. Increased extracellular tonicity effected a time-dependent reduction in eNOS and iNOS protein levels, eNOS mRNA levels, and eNOS gene promoter activity over the first 8 h of the incubation. Although levels of the eNOS mRNA and promoter activity had returned to normal after 24 h, eNOS protein levels remained low at 24-36 h, and recovery was not complete even at 48 h. The decrease in eNOS expression was signaled in large part through a p38 MAPK-dependent mechanism. Reduction in eNOS expression together with the concomitant decline in intracellular cyclic GMP levels appears to account for a significant portion of the p38 MAPK-dependent osmotic stimulation of NPR-A gene expression noted previously. Collectively, these findings support the existence of a complex regulatory circuitry in the cells of the inner medullary collecting duct linking two independent cyclic GMP-generating signal transduction systems involved in regulation of urinary sodium concentration.
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PMID:Osmoregulation of endothelial nitric-oxide synthase gene expression in inner medullary collecting duct cells. Role in activation of the type A natriuretic peptide receptor. 1208 97

We have shown in previous studies that high extracellular tonicity is associated with increased expression of the type A natriuretic peptide receptor (NPR-A) and reduced expression of the endothelial NO synthase (eNOS) gene in cultured rat inner-medullary collecting duct cells. The vasoactive peptide endothelin has been shown to be avidly expressed in this nephron segment, and to be subject to osmotic regulation. We asked whether endothelin might play a role in the control of basal or osmotically regulated NPR-A or eNOS gene expression in these cells. Although exogenous endothelin had little or no effect on basal expression of eNOS mRNA or protein or NPR-A gene expression, both the type A (BQ610) and type B (IRL1038) endothelin receptor antagonists proved capable of reducing eNOS mRNA and protein expression, and increasing levels of the NPR-A mRNA. Increased extracellular tonicity reduced endothelin mRNA accumulation in these cells (approximately 15% of control levels); however, exogenous endothelin failed to normalize osmotically increased NPR-A activity or expression, or osmotically suppressed eNOS expression. Collectively, these data demonstrate the presence of a number of independent but highly interactive local regulatory networks governing fluid and electrolyte handling in this distal nephron segment.
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PMID:Endothelin inhibits NPR-A and stimulates eNOS gene expression in rat IMCD cells. 1262 78

We have shown previously that increased extracellular osmolality stimulates expression and promoter activity of the type A natriuretic peptide receptor (NPR-A) gene in rat inner medullary collecting duct (IMCD) cells through a mechanism that involves activation of p38 mitogen-activated protein kinase (MAPK). The serum and glucocorticoid inducible kinase (Sgk) is thought to participate in the regulation of sodium handling in distal tubular segments. We sought to determine whether this kinase might be involved in the osmotic stimulation of NPR-A gene promoter activity. Exposure of cultured IMCD cells to an additional 75 mmol/L NaCl in culture media (final osmolality 475 mosm/kg) resulted in an approximately 4-fold increase in Sgk1 protein levels after 7 hours. The Sgk1 induction was almost completely inhibited by the p38 MAPK inhibitor SB203580, indicating that NaCl activates Sgk1 through the p38 MAPK pathway. Transient transfection of a mouse Sgk1 expression vector along with a -1590 NPR-A luciferase reporter resulted in an approximately 3-fold increment in reporter activity, which was significantly reduced by cotransfection with a kinase-dead Sgk1 mutant. The NaCl-dependent induction was partially blocked (approximately 40% inhibition) by cotransfection of the kinase-dead Sgk1 mutant. Neither Sgk1 nor the kinase-dead mutant had any effect on endothelial nitric oxide synthase (eNOS) promoter activity, and the Sgk1 mutant and 8-bromo-cyclic guanosine monophosphate were, to some degree, additive in reducing osmotically stimulated NPR-A promoter activity. Collectively, these data imply that Sgk1 operates over an eNOS-independent, p38 MAPK-dependent pathway in mediating osmotic induction of the NPR-A gene promoter.
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PMID:Sgk1 mediates osmotic induction of NPR-A gene in rat inner medullary collecting duct cells. 1500 40

Vitamin D receptor (VDR) modulators are used to treat hyperparathyroidism secondary to chronic kidney disease (CKD). The therapy is associated with reduced mortality in stage 5 CKD patients, who experience an extremely high cardiovascular disease (CVD)-related mortality rate. Chen et al. report that VDR is involved in regulating type A natriuretic peptide receptor (NPR-A) in inner medullary collecting duct cells. The regulation of NPR-A may be one of several mechanisms by which VDR activation reduces CVD risk in CKD.
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PMID:Vitamin D receptor: a highly versatile nuclear receptor. 1744 Apr 94