Cyclooxygenase‐2 and macula densa control of renin secretion

Schnermann, Jürgen

doi:10.1093/ndt/16.9.1735

Cited by 30 publications

(22 citation statements)

References 34 publications

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“…Inhibition of MD Na:2Cl:K cotransport with furosemide prevented [NaCl] L -dependent increases in HEK/EP 1 [Ca 2+ ] i (Figure 3b), consistent with earlier findings that furosemide blocks MD NaCl transport dependency of renin release (27). Low distal tubular [NaCl] is associated with states of volume depletion and is a stimulus for MD signaling that increases synthesis and release of renin from juxtaglomerular granular cells (3)(4)(5)(6). Basolateral MD PGE 2 release in response to decreased luminal salt delivery represents the physiological direction of signal transmission from MD cells into the juxtaglomerular apparatus area.…”

Section: Discussionsupporting

confidence: 89%

“…Basolateral MD PGE 2 release in response to decreased luminal salt delivery represents the physiological direction of signal transmission from MD cells into the juxtaglomerular apparatus area. Recent evidence has accumulated that this signaling mechanism involves MD-derived PGs produced by COX-2 in these cells (3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Consistent with this, we found that HEK/EP 1 calcium responses were inhibited by luminal addition of a selective COX-2 inhibitor (SC58236) or bath SC51322, a blocker of the PGE 2 receptor EP 1 .…”

Section: Discussionsupporting

confidence: 86%

“…In the renal cortex, COX-1 expression predominates in collecting duct, vascular tissue, and glomerular mesangial cells (1). In contrast, COX-2 is expressed and presumably mediates PG production in the macula densa (MD) and surrounding cortical thick ascending limb (cTAL) cells (2)(3)(4)(5). MD cells are in direct contact with the vascular pole of the same glomerulus from which the filtrate originates.…”

mentioning

confidence: 99%

“…These cells sense changes in tubular [NaCl] and send signals that control preglomerular vascular resistance and glomerular filtration rate in a process known as tubuloglomerular feedback. MD cells also control the release of renin from juxtaglomerular granular cells (3)(4)(5)(6). COX-2-derived PGs may participate in MD-mediated control of juxtaglomerular function, particularly in high renin states such as low salt intake, loop diuretic treatment, and renovascular hypertension (4,7).…”

mentioning

confidence: 99%

“…COX-2-derived PGs may participate in MD-mediated control of juxtaglomerular function, particularly in high renin states such as low salt intake, loop diuretic treatment, and renovascular hypertension (4,7). In particular, PGE 2 produced by MD cells has been suggested as the mediator of renin release induced by low luminal [NaCl] ([NaCl] L ) (3)(4)(5)(6)(7)(8)(9)(10). In addition, PGE 2 , as a potent vasodilator, may also modulate preglomerular vascular resistance (11)(12)(13) and tubuloglomerular feedback (14).…”

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confidence: 99%

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Luminal NaCl delivery regulates basolateral PGE2 release from macula densa cells

Peti‐Peterdi¹,

Komlósi²,

Fuson³

et al. 2003

J. Clin. Invest.

128

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Macula densa (MD) cells express COX-2 and COX-2–derived PGs appear to signal the release of renin from the renal juxtaglomerular apparatus, especially during volume depletion. However, the synthetic machinery and identity of the specific prostanoid released from intact MD cells remains uncertain. In the present studies, a novel biosensor tool was engineered to directly determine whether MD cells release PGE2 in response to low luminal NaCl concentration ([NaCl]L). HEK293 cells were transfected with the Ca2+-coupled E-prostanoid receptor EP1 (HEK/EP1) and loaded with fura-2. HEK/EP1 cells produced a significant elevation in intracellular [Ca2+] ([Ca2+]i) by 29.6 ± 12.8 nM (n = 6) when positioned at the basolateral surface of isolated perfused MD cells and [NaCl]L was reduced from 150 mM to zero. HEK/EP1 [Ca2+]i responses were observed mainly in preparations from rabbits on a low-salt diet and were completely inhibited by either a selective COX-2 inhibitor or an EP1 antagonist, and also by 100 μM luminal furosemide. Also, 20-mM graduated reductions in [NaCl]L between 80 and 0 mM caused step-by-step increases in HEK/EP1 [Ca2+]i. Low-salt diet greatly increased the expression of both COX-2 and microsome-associated PGE synthase (mPGES) in the MD. These studies provide the first direct evidence that intact MD cells synthesize and release PGE2 during reduced luminal salt content and suggest that this response is important in the control of renin release and renal vascular resistance during salt deprivation

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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 86%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Luminal NaCl delivery regulates basolateral PGE2 release from macula densa cells

Peti‐Peterdi¹,

Komlósi²,

Fuson³

et al. 2003

J. Clin. Invest.

128

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Renal System

2012

Comparative Pathophysiology and Toxicology of Cyclooxygenases

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Cyclooxygenase Metabolites in the Kidney

Harris

Zhang

2011

Comprehensive Physiology

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In the mammalian kidney, prostaglandins (PGs) are important mediators of physiologic processes, including modulation of vascular tone and salt and water. PGs arise from enzymatic metabolism of free arachidonic acid (AA), which is cleaved from membrane phospholipids by phospholipase A2 activity. The cyclooxygenase (COX) enzyme system is a major pathway for metabolism of AA in the kidney. COX are the enzymes responsible for the initial conversion of AA to PGG2 and subsequently to PGH2, which serves as the precursor for subsequent metabolism by PG and thromboxane synthases. In addition to high levels of expression of the "constitutive" rate-limiting enzyme responsible for prostanoid production, COX-1, the "inducible" isoform of cyclooxygenase, COX-2, is also constitutively expressed in the kidney and is highly regulated in response to alterations in intravascular volume. PGs and thromboxane A2 exert their biological functions predominantly through activation of specific 7-transmembrane G-protein-coupled receptors. COX metabolites have been shown to exert important physiologic functions in maintenance of renal blood flow, mediation of renin release and regulation of sodium excretion. In addition to physiologic regulation of prostanoid production in the kidney, increases in prostanoid production are also seen in a variety of inflammatory renal injuries, and COX metabolites may serve as mediators of inflammatory injury in renal disease.

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Cyclooxygenase‐2 and macula densa control of renin secretion

Cited by 30 publications

References 34 publications

Luminal NaCl delivery regulates basolateral PGE2 release from macula densa cells

Luminal NaCl delivery regulates basolateral PGE2 release from macula densa cells

Renal System

Cyclooxygenase Metabolites in the Kidney

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