Flow regulation of endothelin-1 production in the inner medullary collecting duct
| Autor: | Shali Zhang, Luca Gusella, Rajeev Rohatgi, Edward W. Inscho, Donald E. Kohan, Meghana M. Pandit, Tsugio Seki, Bellamkonda K. Kishore |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Epithelial sodium channel medicine.medical_specialty TRPP Cation Channels Physiology Natriuresis Diuresis Cell Line Rats Sprague-Dawley Mice Transient Receptor Potential Channels Internal medicine Extracellular fluid medicine Animals Calcium Signaling RNA Messenger Kidney Tubules Collecting Epithelial Sodium Channels Autocrine signalling Kidney Medulla Endothelin-1 Chemistry Reabsorption Sodium Receptors Purinergic Water Endothelin 1 Endocrinology Calcium Endothelin receptor |
| Zdroj: | American Journal of Physiology-Renal Physiology. 308:F541-F552 |
| ISSN: | 1522-1466 1931-857X |
| DOI: | 10.1152/ajprenal.00456.2014 |
| Popis: | Collecting duct-derived endothelin (ET)-1 is an autocrine inhibitor of Na+ and water reabsorption; its deficiency causes hypertension and water retention. Extracellular fluid volume expansion increases collecting duct ET-1, thereby promoting natriuresis and diuresis; however, how this coupling between volume expansion and collecting duct ET-1 occurs is incompletely understood. One possibility is that volume expansion increases tubular fluid flow. To investigate this, cultured IMCD3 cells were subjected to static or flow conditions. Exposure to a shear stress of 2 dyn/cm2 for 2 h increased ET-1 mRNA content by ∼2.3-fold. Absence of perfusate Ca2+, chelation of intracellular Ca2+, or inhibition of Ca2+ signaling (calmodulin, Ca2+/calmodulin-dependent kinase, calcineurin, PKC, or phospholipase C) prevented the flow response. Evaluation of possible flow-activated Ca2+ entry pathways revealed no role for transient receptor potential (TRP)C3, TRPC6, and TRPV4; however, cells with TRPP2 (polycystin-2) knockdown had no ET-1 flow response. Flow increased intracellular Ca2+ was blunted in TRPP2 knockdown cells. Nonspecific blockade of P2 receptors, as well as specific inhibition of P2X7 and P2Y2 receptors, prevented the ET-1 flow response. The ET-1 flow response was not affected by inhibition of either epithelial Na+ channels or the mitochondrial Na+/Ca2+ exchanger. Taken together, these findings provide evidence that in IMCD3 cells, flow, via polycystin-2 and P2 receptors, engages Ca2+-dependent signaling pathways that stimulate ET-1 synthesis. |
| Databáze: | OpenAIRE |
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