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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 2019 (12)

Title and authors Publication Year
Cyclo-Oxygenase (COX) Inhibitors and Cardiovascular Risk: Are Non-Steroidal Anti-Inflammatory Drugs Really Anti-Inflammatory?
S Khan, KL Andrews, JP Chin-Dusting
International journal of molecular sciences 2019
Chondroitin sulfate degradation and eicosanoid metabolism pathways are impaired in focal segmental glomerulosclerosis: Experimental confirmation of an in silico prediction
S Kalantari, M Naji, M Nafar, H Yazdani-Kachooei, N Borumandnia, M Parvin
Bioimpacts 2019
Cardio-renal safety of non-steroidal anti-inflammatory drugs
ZA Radi, KN Khan
The Journal of Toxicological Sciences 2019
Lipid mediators in immune regulation and resolution
DW Gilroy, D Bishop-Bailey
British Journal of Pharmacology 2019
Neurobiology and Therapeutic Potential of Cyclooxygenase-2 (COX-2) Inhibitors for Inflammation in Neuropsychiatric Disorders
R Sethi, N Gómez-Coronado, AJ Walker, OD Robertson, B Agustini, M Berk, S Dodd
Frontiers in Psychiatry 2019
Understanding the Interplay between COX-2 and hTERT in Colorectal Cancer Using a Multi-Omics Analysis
GD Ayiomamitis, G Notas, T Vasilakaki, A Tsavari, S Vederaki, T Theodosopoulos, E Kouroumalis, A Zaravinos
Cancers 2019
Cyclooxygenase-2 in gastrointestinal malignancies: Cyclooxygenases in GI Cancer
GP Nagaraju, BF El-Rayes
Cancer 2019
Evaluation of Glomerular Hemodynamic Function by Empagliflozin in Diabetic Mice using In Vivo Imaging
K Kidokoro, DZ Cherney, A Bozovic, H Nagasu, M Satoh, E Kanda, T Sasaki, N Kashihara
Circulation 2019
Non-steroidal anti-inflammatory drug effects on renal and cardiovascular function: from physiology to clinical practice
A Cabassi, S Tedeschi, S Perlini, I Verzicco, R Volpi, G Gonzi, SD Canale
EUR J PREV CARDIOL 2019
Recent advancement in the discovery and development of COX-2 inhibitors: Insight into biological activities and SAR studies (2008–2019)
V Sharma, P Bhatia, O Alam, MJ Naim, F Nawaz, AA Sheikh, M Jha
Bioorganic chemistry 2019
Formation of HETE-EAs and dihydroxy derivatives in mouse kidney tissue and analysis by high-performance liquid chromatography tandem mass spectrometry
SK Dempsey, AM Gesseck, A Ahmad, Z Daneva, JK Ritter, JL Poklis
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 2019
Impact of kolaviron(a biflavonoid) on lipid peroxidation, thromboxane and cyclooxygenase activity in dexamethasone treated ats
EE Nkanu, UP Ujong, GU Otu, A Etetim
2019

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