| Regulation of Na-K-ATPase activity in the proximal tubule: role of the protein kinase C pathway and of eicosanoids. | |
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MedLine Citation:
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PMID: 8672085 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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To evaluate further the signal transduction mechanisms involved in the short-term modulation of Na-K-ATPase activity in the mammalian kidney, we examined the role of phospholipase C-protein kinase C (PLC-PKC) pathway and of various eicosanoids in this process, using microdissected rat proximal convoluted tubules. Dopamine (DA) and parathyroid hormone (either synthetic PTH1-34 or PTH3-34) inhibited Na-K-ATPase activity in dose-dependent manner; this effect was reproduced by PKC530-558 fragment and blocked by the specific PKC inhibitor calphostin C, as well as by the PLC inhibitors neomycin and U-73122. Pump inhibition by DA, PTH, or arachidonic acid, and by PKC activators phorbol dibutyrate (PDBu) or dioctanoyl glycerol (DiC8) was abolished by ethoxyresorufin, an inhibitor of the cytochrome P450-dependent monooxygenase pathway, but was unaffected by indomethacin or nordihydroguaiaretic acid, inhibitors of the cyclooxygenase and lipoxygenase pathways of the arachidonic acid cascade, respectively. Furthermore, each of the three monooxygenase products tested (20-HETE, 12(R)-HETE, or 11,12-DHT) caused a dose-dependent inhibition of the pump. The effect of DA, PTH, PDBu or DiC8, as well as that of 20-HETE was not altered when sodium entry was blocked with the amiloride analog ethylisopropyl amiloride or increased with nystatin. We conclude that short-term regulation of proximal tubule Na-K-ATPase activity by dopamine and parathyroid hormone occurs via the PLC-PKC signal transduction pathway and is mediated by cytochrome P450-dependent monooxygenase products of arachidonic acid metabolism, which may interact with the pump rather than alter sodium access to it. |
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Authors:
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M Ominato; T Satoh; A I Katz |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Journal of membrane biology Volume: 152 ISSN: 0022-2631 ISO Abbreviation: J. Membr. Biol. Publication Date: 1996 Aug |
Date Detail:
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Created Date: 1996-09-27 Completed Date: 1996-09-27 Revised Date: 2009-11-03 |
Medline Journal Info:
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Nlm Unique ID: 0211301 Medline TA: J Membr Biol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 235-43 Citation Subset: IM |
Affiliation:
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Department of Medicine, University of Chicago Pritzker School of Medicine, Chicago, Illinois 60637, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amiloride
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analogs & derivatives,
pharmacology Animals Dopamine / pharmacology Eicosanoids / pharmacology* Enzyme Inhibitors / pharmacology Estrenes / pharmacology Homeostasis Indomethacin / pharmacology Kidney Tubules, Proximal / enzymology* Kinetics Male Models, Biological Naphthalenes / pharmacology Neomycin / pharmacology Nordihydroguaiaretic Acid / pharmacology Nystatin / pharmacology Oxazines / pharmacology Parathyroid Hormone / pharmacology Peptide Fragments / pharmacology Protein Kinase C / antagonists & inhibitors, metabolism* Pyrrolidinones / pharmacology Rats Rats, Sprague-Dawley Signal Transduction Sodium-Potassium-Exchanging ATPase / metabolism* Teriparatide Type C Phospholipases / antagonists & inhibitors |
| Chemical | |
Reg. No./Substance:
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0/Eicosanoids; 0/Enzyme Inhibitors; 0/Estrenes; 0/Naphthalenes; 0/Oxazines; 0/Parathyroid Hormone; 0/Peptide Fragments; 0/Pyrrolidinones; 112648-68-7/1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; 1154-25-2/ethylisopropylamiloride; 121263-19-2/calphostin C; 1400-61-9/Nystatin; 1404-04-2/Neomycin; 2609-46-3/Amiloride; 500-38-9/Nordihydroguaiaretic Acid; 51257-86-4/parathyroid hormone (3-34); 52232-67-4/Teriparatide; 53-86-1/Indomethacin; 5725-91-7/ethoxyresorufin; EC 2.7.11.13/Protein Kinase C; EC 3.1.4.-/Type C Phospholipases; EC 3.6.3.9/Sodium-Potassium-Exchanging ATPase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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