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Citations to this article

Cyclooxygenase-2 is associated with the macula densa of rat kidney and increases with salt restriction.
R C Harris, … , R N Dubois, M D Breyer
R C Harris, … , R N Dubois, M D Breyer
Published December 1, 1994
Citation Information: J Clin Invest. 1994;94(6):2504-2510. https://doi.org/10.1172/JCI117620.
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Research Article

Cyclooxygenase-2 is associated with the macula densa of rat kidney and increases with salt restriction.

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Abstract

The kidney is a rich source of prostaglandins. These eicosanoids, formed by cyclooxygenase-dependent metabolism of arachidonic acid, are important physiologic mediators of renal glomerular hemodynamics and tubular sodium and water reabsorption. Two separate isoforms of cyclooxygenase (COX) have now been identified: constitutive COX-1, encoded by a 2.8-kb mRNA, and mitogen-activated COX-2, encoded by a 4.0-4.5-kb mRNA. COX-2 expression increases during development and inflammation, but, except for brain, constitutive expression is low. It has been generally accepted that physiologic renal production of prostaglandins is mediated by COX-1. However, in the absence of inflammation, low levels of COX-2 mRNA are also detectable in the kidney. To examine the role of COX-2 in the kidney and determine its intrarenal localization, we used a 1.3-kb cDNA probe specific for the 3' untranslated region of rat COX-2 and COX-2-specific antiserum. The COX-2-specific cDNA probe hybridized with a 4.4-kb transcript in total RNA from adult rat kidney. Immunoblots of microsomes isolated from kidney cortex and papilla indicated immunoreactive COX-2 in both locations. In situ hybridization and immunohistochemistry indicated that renal cortical COX-2 expression was localized to the macula densa of the juxtaglomerular apparatus and to adjacent epithelial cells of the cortical thick ascending limb of Henle. In addition, COX-2 immunoreactivity was detected in interstitial cells in the papilla. No COX-2 message or immunoreactive protein was detected in arterioles, glomeruli, or cortical or medullary collecting ducts. When animals were chronically sodium restricted, the level of COX-2 in the region of the macula densa increased threefold (from 0.86 +/- 0.08 to 2.52 +/- 0.43/mm2) and the total area of the COX-2 immunoreactive cells in cortex increased from 34 microns2/mm2 of cortex to 226 microns2/mm2 of cortex. The intrarenal distribution of COX-2 and its increased expression in response to sodium restriction suggest that in addition to its proposed role in inflammatory and growth responses, this enzyme may play an important role in the regulation of salt, volume, and blood pressure homeostasis.

Authors

R C Harris, J A McKanna, Y Akai, H R Jacobson, R N Dubois, M D Breyer

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 1998 1997 1996 1995 1986 Total
Citations: 1 2 1 3 6 6 12 5 16 10 6 16 16 29 22 17 20 24 27 34 32 35 49 66 45 53 42 28 17 12 5 1 658
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Citations to this article in year 2015 (6)

Title and authors Publication Year
Inhibition of Cyclooxygenase-2 Derived Prostaglandin E2 Signaling in Hematopoietic Cells Results in Salt-Sensitive Hypertension
Ming-zhi Zhang, Bing Yao, Yinqiu Wang, shilin Yang, Suwan Wang, Xiaofeng Fan, Harris Raymond Clement
Journal of Clinical Investigation 2015
Salt Restriction Leads to Activation of Adult Renal Mesenchymal Stromal Cell-Like Cells via Prostaglandin E2 and E-Prostanoid Receptor 4
Y Yang, JA Gomez, M Herrera, R Perez-Marco, P Repenning, Z Zhang, A Payne, RE Pratt, B Koller, WH Beierwaltes, T Coffman, M Mirotsou, VJ Dzau
Hypertension 2015
Effect of Cyclooxygenase(COX)-1 and COX-2 inhibition on furosemide-induced renal responses and isoform immunolocalization in the healthy cat kidney
L Pelligand, N Suemanotham, JN King, W Seewald, H Syme, K Smith, P Lees, J Elliott
BMC veterinary research 2015
Early co-expression of cyclooxygenase-2 and renin in the rat kidney cortex contributes to the development of N G -nitro- l -arginine methyl ester induced hypertension
EA Guzmán-Hernández, R Villalobos-Molina, MA Sánchez-Mendoza, LD Valle-Mondragón, G Pastelín-Hernández, M Ibarra-Barajas
Canadian Journal of Physiology and Pharmacology 2015
Anti-Diabetic and Anti-Inflammatory Potential of the Edible Brown Alga H izikia Fusiformis: Anti-Diabetic and Anti-Inflammatory Activities of Hizikia Fusiformis
YR Han, MY Ali, MH Woo, HA Jung, JS Choi
Journal of Food Biochemistry 2015
Pathophysiology and Pharmacotherapy of Cardiovascular Disease
G Jagadeesh, P Balakumar, K Maung-U
2015

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