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

Raymond C. Harris, James A. McKanna, Yoichi Akai, Harry R. Jacobson, Raymond N. Dubois, Matthew D. Breyer

Research output: Contribution to journalArticle

785 Citations (Scopus)

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 μm2/mm2 of cortex to 226 μm2/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.

Original languageEnglish (US)
Pages (from-to)2504-2510
Number of pages7
JournalJournal of Clinical Investigation
Volume94
Issue number6
StatePublished - Dec 1994
Externally publishedYes

Fingerprint

Cyclooxygenase 2
Salts
Kidney
Cyclooxygenase 1
Sodium
Prostaglandin-Endoperoxide Synthases
Messenger RNA
Prostaglandins
Complementary DNA
Juxtaglomerular Apparatus
Kidney Medulla
Kidney Cortex
Eicosanoids
Arterioles
3' Untranslated Regions
Encephalitis
Microsomes
Mitogens
Arachidonic Acid
In Situ Hybridization

Keywords

  • juxtaglomerular
  • macula densa
  • prostaglandin
  • prostaglandin synthase
  • renin

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Harris, R. C., McKanna, J. A., Akai, Y., Jacobson, H. R., Dubois, R. N., & Breyer, M. D. (1994). Cyclooxygenase-2 is associated with the macula densa of rat kidney and increases with salt restriction. Journal of Clinical Investigation, 94(6), 2504-2510.

Cyclooxygenase-2 is associated with the macula densa of rat kidney and increases with salt restriction. / Harris, Raymond C.; McKanna, James A.; Akai, Yoichi; Jacobson, Harry R.; Dubois, Raymond N.; Breyer, Matthew D.

In: Journal of Clinical Investigation, Vol. 94, No. 6, 12.1994, p. 2504-2510.

Research output: Contribution to journalArticle

Harris, RC, McKanna, JA, Akai, Y, Jacobson, HR, Dubois, RN & Breyer, MD 1994, 'Cyclooxygenase-2 is associated with the macula densa of rat kidney and increases with salt restriction', Journal of Clinical Investigation, vol. 94, no. 6, pp. 2504-2510.
Harris RC, McKanna JA, Akai Y, Jacobson HR, Dubois RN, Breyer MD. Cyclooxygenase-2 is associated with the macula densa of rat kidney and increases with salt restriction. Journal of Clinical Investigation. 1994 Dec;94(6):2504-2510.
Harris, Raymond C. ; McKanna, James A. ; Akai, Yoichi ; Jacobson, Harry R. ; Dubois, Raymond N. ; Breyer, Matthew D. / Cyclooxygenase-2 is associated with the macula densa of rat kidney and increases with salt restriction. In: Journal of Clinical Investigation. 1994 ; Vol. 94, No. 6. pp. 2504-2510.
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