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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
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Citations to this article in year 2008 (24)

Title and authors Publication Year
Non-redundant functions of cyclooxygenases: oxygenation of endocannabinoids
CA Rouzer, LJ Marnett
The Journal of biological chemistry 2008
Increased dietary NaCl induces renal medullary PGE2 production and natriuresis via the EP2 receptor
J Chen, M Zhao, W He, GL Milne, JR Howard, J Morrow, RL Hébert, RM Breyer, J Chen, CM Hao
American journal of physiology. Renal physiology 2008
Renal Effects of Prostaglandins and Cyclooxygenase-2 Inhibitors
GH Kim
Electrolyte & blood pressure : E & BP 2008
Physiological Regulation of Prostaglandins in the Kidney
CM Hao, MD Breyer
Annual Review of Physiology 2008
Effects of a non-selective COX inhibitor and selective COX-2 inhibitors on contractility of human and porcine uretersin vitroandin vivo
V Chaignat, H Danuser, MH Stoffel, S Z'brun, UE Studer, M Mevissen
British Journal of Pharmacology 2008
Expression of COX-1, COX-2, iNOS and p38 in Human Brain with Stroke Lesions
ZA Radi, NK Khan
International Journal of Pharmacology 2008
Hypertension in rheumatoid arthritis
VF Panoulas, GS Metsios, AV Pace, H John, GJ Treharne, MJ Banks, GD Kitas
Rheumatology 2008
Cardiovascular risks of COX inhibition: current perspectives
M Farooq, I Haq, AS Qureshi
Expert Opinion on Pharmacotherapy 2008
Gene Duplications and Losses within the Cyclooxygenase Family of Teleosts and Other Chordates
JC Havird, MM Miyamoto, KP Choe, DH Evans
Molecular Biology and Evolution 2008
An update on cyclooxygenase-2 expression and metabolites in the kidney
RC Harris
Current Opinion in Nephrology and Hypertension 2008
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J Zacher, R Altman, N Bellamy, P Brühlmann, JD Silva, E Huskisson, RS Taylor
Current Medical Research and Opinion 2008
Risk management profile of etoricoxib: an example of personalized medicine
P Patrignani, S Tacconelli, ML Capone
Therapeutics and Clinical Risk Management 2008
Renal effect of meloxicam versus ketoprofen in anaesthetized pseudo-normovolaemic piglets
S Junot, É Troncy, S Keroack, D Gauvin, JR Castillo, R Boivin, JM Bonnet
Canadian Journal of Physiology and Pharmacology 2008
Microcirculation
K Ley
Microcirculation 2008
Manual of Hypertension of The European Society of Hypertension: other humoral-endocrine factors
M Burnier
Manual of Hypertension of The European Society of Hypertension: other humoral-endocrine factors 2008
Early postnatal ibuprofen and indomethacin effects in suckling and weanling rat kidneys
J Hasan, KD Beharry, Z Gharraee, Y Stavitsky, P Abad-Santos, M Abad-Santos, JV Aranda, HD Modanlou
Prostaglandins & Other Lipid Mediators 2008
Non-redundant Functions of Cyclooxygenases: Oxygenation of Endocannabinoids
CA Rouzer, LJ Marnett
The Journal of biological chemistry 2008
Increased dietary NaCl induces renal medullary PGE 2 production and natriuresis via the EP2 receptor
J Chen, M Zhao, W He, GL Milne, JR Howard, J Morrow, RL Hébert, RM Breyer, J Chen, CM Hao
American journal of physiology. Renal physiology 2008
Site-specific Expression of IQGAP1, a Key Mediator of Cytoskeleton, in Mouse Renal Tubules
LW Lai, KC Yong, YH Lien
Journal of Histochemistry & Cytochemistry 2008
Renal localization and regulation of 15-hydroxyprostaglandin dehydrogenase
B Yao, J Xu, RC Harris, MZ Zhang
American journal of physiology. Renal physiology 2008
Review: Adverse cardiovascular effects of NSAIDs: driven by blood pressure, or edema?
A Aneja, ME Farkouh
Therapeutic advances in cardiovascular disease 2008
Renoprotective effects of neuronal NOS-derived nitric oxide and cyclooxygenase-2 metabolites in transgenic rats with inducible malignant hypertension
ME Patterson, JJ Mullins, KD Mitchell
American journal of physiology. Renal physiology 2008
Clinical Nephrotoxins
ME Broe, GA Porter, WM Bennett, G Deray
2008
Sensitization of Cancer Cells for Chemo/Immuno/Radio-therapy
B Bonavida
2008

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