Source:http://linkedlifedata.com/resource/pubmed/id/12709393
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
2003-7-4
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pubmed:abstractText |
Recently, we described a splice variant of the human natriuretic peptide receptor type B (NPR-Bi) in human proximal tubule cells [immortalized human kidney epithelial cells (IHKE-1) that lacks a functional guanylate cyclase domain (Hirsch JR, Meyer M, Mägert HJ, Forssmann WG, Mollerup S, Herter P, Weber G, Cermak R, Ankorina-Stark I, Schlatter E, and Kruhøffer M. J Am Soc Nephrol 10: 472-480, 1999). Its signaling pathway does not include cGMP, cAMP, or Ca2+ but leads to inhibition of K+ channels. In patch-clamp experiments, effects of tyrosine kinase receptor blockers on C-type natriuretic peptide (CNP)-mediated depolarizations of membrane voltages (Vm) of IHKE-1 cells were tested. The epidermal growth factor (EGF) receptor blocker genistein (10 microM) abolished the effect of CNP (0.2 +/- 0.4 mV, n = 7), and comparable results were obtained with 10 microM daidzein (n = 8). Aminogenistein (10 microM, n = 5) and tyrphostin AG1295 (10 microM, n = 5) had no significant effects. EGF (1 nM) hyperpolarized cells by -5.3 +/- 0.8 mV (n = 5). This effect was completely blocked by genistein or daidzein. The Cl- channel blocker NPPB (10 microM, n = 5) inhibited the EGF-mediated hyperpolarization. mRNA expression of NPR-B and NPR-Bi shows reversed patterns along the human nephron. NPR-B is highly expressed in glomeruli and proximal tubules, whereas NPR-Bi shows strong signals in the distal nephron. Expression of NPR-Bi in the cortical collecting duct was also confirmed with immunohistochemistry. In other human tissues, NPR-Bi shows strongest expression in pancreas and lung, whereas in the heart and liver NPR-B is the dominating receptor. In conclusion, CNP inhibits an apical K+ channel in IHKE-1 cells independently of cGMP and so far this effect can only be blocked by genistein and daidzein. Tyrosine phosphorylation might be the missing link in the signaling pathway of CNP/NPR-Bi.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/6,7-dimethoxy-2-phenylquinoxaline,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic GMP,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Estrogens, Non-Steroidal,
http://linkedlifedata.com/resource/pubmed/chemical/Genistein,
http://linkedlifedata.com/resource/pubmed/chemical/Guanylate Cyclase,
http://linkedlifedata.com/resource/pubmed/chemical/Isoflavones,
http://linkedlifedata.com/resource/pubmed/chemical/Natriuretic Peptide, C-Type,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Atrial Natriuretic Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrphostins,
http://linkedlifedata.com/resource/pubmed/chemical/atrial natriuretic factor receptor B,
http://linkedlifedata.com/resource/pubmed/chemical/daidzein
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1931-857X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
285
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
F370-4
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pubmed:dateRevised |
2011-4-28
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pubmed:meshHeading |
pubmed-meshheading:12709393-Cell Line, Transformed,
pubmed-meshheading:12709393-Cyclic GMP,
pubmed-meshheading:12709393-Enzyme Inhibitors,
pubmed-meshheading:12709393-Estrogens, Non-Steroidal,
pubmed-meshheading:12709393-Gene Expression,
pubmed-meshheading:12709393-Genistein,
pubmed-meshheading:12709393-Guanylate Cyclase,
pubmed-meshheading:12709393-Humans,
pubmed-meshheading:12709393-Isoflavones,
pubmed-meshheading:12709393-Kidney Tubules,
pubmed-meshheading:12709393-Natriuretic Peptide, C-Type,
pubmed-meshheading:12709393-Patch-Clamp Techniques,
pubmed-meshheading:12709393-Potassium,
pubmed-meshheading:12709393-RNA Splicing,
pubmed-meshheading:12709393-Receptors, Atrial Natriuretic Factor,
pubmed-meshheading:12709393-Signal Transduction,
pubmed-meshheading:12709393-Tyrphostins
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pubmed:year |
2003
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pubmed:articleTitle |
Signaling and distribution of NPR-Bi, the human splice form of the natriuretic peptide receptor type B.
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pubmed:affiliation |
Medizinische Klinik und Poliklinik D, Experimentelle Nephrologie, Domagkstr. 3a, D-48149 Münster, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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