Na delivery and ENaC mediate flow regulation of collecting duct endothelin-1 production
| Autor: | Donald E. Kohan, Toshio Matsuda, Meghana M. Pandit, Kevin A. Strait |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Epithelial sodium channel
medicine.medical_specialty Kidney Cortex Physiology Autocrine Communication Cell Line Mice Chlorides Internal medicine Extracellular fluid medicine Animals RNA Messenger Kidney Tubules Collecting Epithelial Sodium Channels Autocrine signalling Water transport Endothelin-1 Chemistry Cell Membrane Osmolar Concentration Sodium Extracellular Fluid Articles Water-Electrolyte Balance Endothelin 1 Mitochondria Cell biology Tubule Endocrinology medicine.anatomical_structure Duct (anatomy) |
| Zdroj: | American Journal of Physiology-Renal Physiology. 302:F1325-F1330 |
| ISSN: | 1522-1466 1931-857X |
| DOI: | 10.1152/ajprenal.00034.2012 |
| Popis: | Collecting duct (CD) endothelin-1 (ET-1) is an important autocrine inhibitor of Na and water transport. CD ET-1 production is stimulated by extracellular fluid volume expansion and tubule fluid flow, suggesting a mechanism coupling CD Na delivery and ET-1 synthesis. A mouse cortical CD cell line, mpkCCDc14, was subjected to static or flow conditions for 2 h at 2 dyn/cm2, followed by determination of ET-1 mRNA content. Flow with 300 mosmol/l NaCl increased ET-1 mRNA to 65% above that observed under static conditions. Increasing perfusate osmolarity to 450 mosmol/l with NaCl or Na acetate increased ET-1 mRNA to ∼184% compared with no flow, which was not observed when osmolarity was increased using mannitol or urea. Reducing Na concentration to 150 mosmol/l while maintaining total osmolarity at 300 mosmol/l with urea or mannitol decreased the flow response. Inhibition of epithelial Na channel (ENaC) with amiloride or benzamil abolished the flow response, suggesting involvement of ENaC in flow-regulated ET-1 synthesis. Aldosterone almost doubled the flow response. Since Ca2+ enhances CD ET-1 production, the involvement of plasma membrane and mitochondrial Na/Ca2+ exchangers (NCX) was assessed. SEA0400 and KB-R7943, plasma membrane NCX inhibitors, did not affect the flow response. However, CGP37157, a mitochondrial NCX inhibitor, abolished the response. In summary, the current study indicates that increased Na delivery, leading to ENaC-mediated Na entry and mitochondrial NCX activity, is involved in flow-stimulated CD ET-1 synthesis. This constitutes the first report of either ENaC or mitochondrial NCX regulation of an autocrine factor in any biologic system. |
| Databáze: | OpenAIRE |
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