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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2003-7-4
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
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
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1931-857X
pubmed:author
pubmed:issnType
Print
pubmed:volume
285
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
F370-4
pubmed:dateRevised
2011-4-28
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Signaling and distribution of NPR-Bi, the human splice form of the natriuretic peptide receptor type B.
pubmed:affiliation
Medizinische Klinik und Poliklinik D, Experimentelle Nephrologie, Domagkstr. 3a, D-48149 Münster, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't