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Articles in PresS, published online ahead of print April 30, 2002
Am J Physiol Renal Physiol, 10.1152/ajprenal.00236.2001
Submitted on July 30, 2001
Accepted on April 4, 2002
1 Department of Cell Biology, Vanderbilt Universtiy, Nashville, TN, USA
2 Department of Medicine, Vanderbilt University, Nashville, TN, USA
* To whom correspondence should be addressed. E-mail: jim.mckanna{at}mcmail.vanderbilt.edu.
The renal inner medulla and its distal one-third, the papilla, are major sites of prostanoids synthesis involved in water and electrolyte homeostasis. These sites contain variable levels of cyclooxygenase-2 (COX-2), a key prostaglandin synthase enzyme that is sensitive to adrenal steroids. Immunoreactive renal medullary COX-2, restricted to interstitial cells in control adult rats, shows a gradient of intense staining at the tip of the papilla that gradually diminishes to undetectable levels in the proximal inner medulla. We used adrenalectomy (ADX) and steroid replacement to investigate the effects of steroids on papillary COX-2. Immunoblots demonstrate that papillary COX-2 was reduced by half after 2wk ADX; glucocorticoid replacement ameliorated the decline but not to control levels. Mineralocorticoid (DOCA) replacement stimulated papillary COX-2 >5-fold over control; both the intensity of immunostaining and the numbers of COX-2-positive cells in the inner medulla increased. Similar stimulation of papillary COX-2 resulted from DOCA treatment of normal control rats, but the response was blunted in rats fed a low-salt diet and absent in Brattleboro rats. DOCA treatment of mouse renal medullary interstitial cells in culture had no effect; but increased tonicity of the culture medium with NaCl caused strong upregulation of COX-2. Urea, a permeant molecule, had no effect. Together, these results suggest that mineralocorticoids lead to upregulation of COX-2 in rat renal medulla by indirect pathways, probably involving induced electrolyte hypertonicity in the interstitial fluid.
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