Immunolocalization of cyclooxygenase‐2 in the macula densa of human elderly

Nantel, F.; Meadows, Emily; Denis, Danielle; Connolly, Brett; Metters, Kathleen M.; Giaid, Adel

doi:10.1016/s0014-5793(99)01088-1

Cited by 117 publications

(92 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…5,6 Furthermore, despite initial controversy regarding COX-2 localization in primate and human kidney, 4,6 more recent studies confirm a similar distribution of COX-2 in MD, especially in the elderly and in patients with diabetes mellitus, congestive heart failure, and Bartter syndrome. 7 COX-2 expression is also abundant in the lipid-laden medullary interstitial cells in the inner medulla and papilla. 5 Some investigators have reported that COX-2 may also be expressed in inner medullary collecting duct cells or intercalated cells in the renal cortex.…”

Section: Expression Of Cox-1 and Cox-2 In The Kidneymentioning

confidence: 98%

Cyclooxygenases, the Kidney, and Hypertension

2004

View full text Add to dashboard Cite

Abstract-Selective cyclooxygenase (COX)-2 inhibitors that are in widespread clinical use were developed to avoid side effects of conventional NSAIDs, including gastrointestinal and renal toxicity. However, COX-2 is constitutively expressed in the kidney and is highly regulated in response to alterations in intravascular volume. COX-2 metabolites have been implicated in maintenance of renal blood flow, mediation of renin release, and regulation of sodium excretion. COX-2 inhibition may transiently decrease urine sodium excretion in some subjects and induce mild to moderate elevation of blood pressure. Furthermore, in conditions of relative intravascular volume depletion and/or renal hypoperfusion, interference with COX-2 activity can have deleterious effects on maintenance of renal blood flow and glomerular filtration rate. In addition to physiological regulation of COX-2 expression in the kidney, increased renal cortical COX-2 expression is seen in experimental models associated with altered renal hemodynamics and progressive renal injury (decreased renal mass, poorly controlled diabetes), and long-term treatment with selective COX-2 inhibitors ameliorates functional and structural renal damage in these conditions. Key Words: COX-2 Ⅲ COX-1 Ⅲ hypertension Ⅲ renin Ⅲ sodium Ⅲ glomerular filtration rate Ⅲ kidney I n the kidney, prostaglandins are important mediators of vascular tone, salt and water balance, and renin release. The rate-limiting enzyme, cyclooxygenase (prostaglandin synthase G 2 /H 2 ) initiates the metabolism of arachidonic acid to prostaglandin (PG) G 2 and subsequently to PGH 2 , which is then further metabolized by tissue-specific isomerases to PGs and thromboxane. There are at least two distinct cyclooxygenases, COX-1 and COX-2, that share Ϸ60% homology 1 but are the products of different genes and have distinct patterns of expression and regulation. COX-1 has been termed "constitutive," because of its wide tissue distribution, while COX-2 has been designated as "inducible" because of its more restricted basal expression and its upregulation by inflammatory and/or proliferative stimuli and its central role in mediation of inflammatory conditions and malignancies. Recently, Chandrasekharan et al characterized a third potential cyclooxygenase isoform, COX-3, a 65-kDa membranebound protein with acetaminophen or paracetamol-sensitive cyclooxygenase activity that represents a splice variant of COX-1. 2 However, other investigators have not confirmed the existence of full-length, catalytically active COX-3 from human genomic clones. Therefore, it remains uncertain whether COX-3 in fact represents the elusive target of paracetamol.Inhibition of COX activity by NSAIDs has been widely used for the treatment of pain and inflammation. Because prostanoids are involved in renal function, nonselective NSAIDs exhibit adverse effects, including salt retention and decreases in glomerular filtration rate (GFR), which may elevate blood pressure (BP) or make pre-existing hypertension worse. 3 Based on the hypothesis...

show abstract

Section: Expression Of Cox-1 and Cox-2 In The Kidneymentioning

confidence: 98%

Cyclooxygenases, the Kidney, and Hypertension

2004

View full text Add to dashboard Cite

show abstract

“…In the renal cortex, there is localized expression of COX-2 mRNA and immunoreactive protein in the cells of the macula densa (MD) and in scattered cells in the cortical thick ascending limb cells immediately adjacent to the MD (13-18) ( Figure 1A). In human kidney, COX-2 expression also has been reported to be present in podocytes and arteriolar smooth muscle cells (12,14,19).…”

Section: Expression Of Cox-1 and Cox-2 In The Kidneymentioning

confidence: 99%

Update on Cyclooxygenase-2 Inhibitors

Harris

Breyer

2006

Clinical Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Nonsteroidal anti-inflammatory drugs represent the most commonly used medications for the treatment of pain and inflammation, but numerous well-described side effects can limit their use. Cyclooxygenase-2 (COX-2) inhibitors were initially touted as a therapeutic strategy to avoid not only the gastrointestinal but also the renal and cardiovascular side effects of nonspecific nonsteroidal anti-inflammatory drugs. However, in the kidney, COX-2 is constitutively expressed and is highly regulated in response to alterations in intravascular volume. COX-2 metabolites have been implicated in mediation of renin release, regulation of sodium excretion, and maintenance of renal blood flow. This review summarizes the current state of knowledge about both renal and cardiovascular side effects that are attributed to COX-2 selective inhibitors.Clin J Am Soc Nephrol 1: 236 -245, 2006236 -245, . doi: 10.2215 N onsteroidal anti-inflammatory drugs (NSAID) are the most commonly used class of medications for the treatment of pain and inflammation and represent one of the most common classes of medications used worldwide, with an estimated usage of Ͼ30 million per day (1). Nonselective NSAID inhibit both constitutive cyclooxygenase-1 (COX-1) and inducible cyclooxygenase-2 (COX-2), the rate-limiting enzymes that are involved in production of prostaglandins and thromboxane. In addition to their role in inflammation, prostaglandins are important regulators of vascular tone, salt and water balance, and renin release, and nonselective NSAID exhibit adverse effects, including salt retention and reduced GFR, which may elevate BP or make pre-existing hypertension worse (2). It has been estimated that as many as 2.5 million Americans experience NSAID-mediated renal effects yearly (3). Risk factors that predispose to NSAID-induced renal functional alterations include age Ͼ65 yr, cardiovascular disease, diabetes, male gender, high NSAID dosage, and concurrent use of other nephrotoxic drugs (3). Up to 20% of patients who take nonselective NSAID and have more than one of these risk factors may manifest alterations in renal function.In addition to renal side effects, nonselective NSAID have long been known to predispose to gastrointestinal (GI) toxicity. It has been estimated that one third of patients who taking long-term nonselective NSAID develop endoscopically proven gastric or duodenal ulcers (4). The risk for serious bleeding from these lesions is somewhat lower, with approximately 100,000 hospitalizations for GI complications of NSAID (5). One study estimated that nonselective NSAID-induced GI abnormalities constitute the 15th leading cause of death in the United States (6). The premise that COX-1 performs cellular "housekeeping" functions for normal physiologic activity and is the predominant isoform expressed in platelets and the GI tract, whereas COX-2 acts at inflammatory sites, led to the development of COX-2 selective inhibitors. It also was originally hypothesized that the renal effects of nonselective NSAID were also linked to COX-...

show abstract

“…The small intestine and kidney, which constitutively expressed COX-2 (16,17) and other key tissues (i.e., liver and lung), were examined for anandamide remaining and for prostamide formation after intravenous bolus administration of 50 mg/kg anandamide to normal mice and FAAH knockout (FAAH Ϫ / Ϫ ) mice.…”

mentioning

confidence: 99%

Formation of prostamides from anandamide in FAAH knockout mice analyzed by HPLC with tandem mass spectrometry

Weber

Ling

et al. 2004

Journal of Lipid Research

116

View full text Add to dashboard Cite

We investigated the formation of PGF 2 ␣ 1-ethanolamide, PGE 2 1-ethanolamide, and PGD 2 1-ethanolamide (prostamides F 2 ␣ , E 2 , and D 2 , respectively) in liver, lung, kidney, and small intestine after a single intravenous bolus administration of 50 mg/kg of anandamide to normal and fatty acid amide hydrolase knockout (FAAH ؊ / ؊ ) male mice. One group of three normal mice was not dosed (naïve) while another group of three normal mice received a bolus intravenous injection of 50 mg/kg of anandamide. Three FAAH ؊ / ؊ mice also received an intravenous injection of 50 mg/kg of anandamide. After 30 min, the lung, liver, kidney, and small intestine were harvested and processed by liquid-liquid extraction. The concentrations of prostamide F 2 ␣ , prostamide E 2 , prostamide D 2 , and anandamide were determined by HPLC-tandem mass spectrometry. Prostamide F 2 ␣ was detected in tissues in FAAH ؊ / ؊ mice after administration of anandamide. Concentrations of anandamide, prostamide E 2 , and prostamide D 2 in liver, kidney, lung, and small intestine were much higher in the anandamide-treated FAAH ؊ / ؊ mice than those of the anandamide-treated control mice.This report demonstrates that prostamides, including prostamide F 2 ␣ , were formed in vivo from anandamide, potentially by the cyclooxygenase-2 pathway when the competing FAAH pathway is lacking.

show abstract

Immunolocalization of cyclooxygenase‐2 in the macula densa of human elderly

Cited by 117 publications

References 21 publications

Cyclooxygenases, the Kidney, and Hypertension

Cyclooxygenases, the Kidney, and Hypertension

Update on Cyclooxygenase-2 Inhibitors

Formation of prostamides from anandamide in FAAH knockout mice analyzed by HPLC with tandem mass spectrometry

Contact Info

Product

Resources

About