Differential regulation of cyclooxygenase isozymes by cAMP-elevating agents

Samokovlisky, Albena; Rimon, Gilad; Danon, Abraham

doi:10.1016/s0014-2999(99)00461-6

Cited by 7 publications

(4 citation statements)

References 34 publications

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“…Increasing cellular AMP inhibited PGHS-1 activity without affecting PGHS-1 expression, but PGHS-2 protein was upregulated. 25 However, PMA-induced expression of PGHS-2 is inhibited by extracellular cAMP in human pulmonary microvascular endothelial cells. 26 A negative feedback loop that regulates PGHS levels may exist in vascular cells that involves the peroxisome proliferator-activated receptor (PPAR).…”

Section: Davidge Pghs and Vascular Function 651mentioning

confidence: 99%

Prostaglandin H Synthase and Vascular Function

Davidge

2001

Circulation Research

207

170

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Abstract-Prostaglandin H synthase (PGHS) is a rate-limiting enzyme in the production of prostaglandins and thromboxane, which are important regulators of vascular function. Under normal physiological conditions, PGHSdependent vasodilators (such as prostacyclin) modulate vascular tone. However, PGHS-dependent vasoconstriction (mediated by thromboxane and/or its immediate precursor, PGH 2 ) predominates in some vascular pathologies (eg, systemic hypertension, diabetes, cerebral ischemia, and aging). This review will discuss the role of PGHS-dependent modulation of vascular function in a number of vascular beds (systemic, pulmonary, cerebral, and uterine) with an emphasis on vascular pathophysiology. Moreover, the specific contributions of the different isoforms (PGHS-1 and PGHS-2) are discussed. Understanding the role of PGHS in vascular function is of particular importance because they are the targets of the commonly used nonsteroidal antiinflammatory drugs (NSAIDs), which include aspirin and ibuprofen. Importantly, with the advent of specific PGHS-2 inhibitors for treatment of conditions such as chronic inflammatory disease, it is an opportune time to review the data regarding PGHS-dependent modulation of vascular function. (Circ Res. 2001;89:650-660.)

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Section: Davidge Pghs and Vascular Function 651mentioning

confidence: 99%

Prostaglandin H Synthase and Vascular Function

Davidge

2001

Circulation Research

207

170

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“…In special, platelet COX-1 activity is known to inhibit by cAMP (Schafer et al , 1980). Considering these reports (Schafer et al , 1980; Samokovlisky et al , 1999), and the effects of EGCG that increases markedly cAMP via adenylate cyclase activation and subsequently phosphorylates VASP-Ser 157 through A-kinase activation to inhibit Ca 2+ -mobilization and TXA 2 production on collagen-induced platelet aggregation (Ok et al , 2012), it is thought that EGCG might involve in inhibition of COX-1 activity (Fig. 2B) by stimulating adenylate cyclase/cAMP/A-kinase/VASP-Ser 157 phosphorylation pathway.…”

Section: Discussionmentioning

confidence: 96%

“…With regard to this, further more study is necessary in the future. It is known that increased cellular cAMP selectively inhibits COX-1 activity without altering COX-1 protein expression in bovine aortic endothelial cells (Samokovlisky et al , 1999). In special, platelet COX-1 activity is known to inhibit by cAMP (Schafer et al , 1980).…”

Section: Discussionmentioning

confidence: 99%

Inhibitory Effects of Epigallocatechin-3-Gallate on Microsomal Cyclooxygenase-1 Activity in Platelets

Lee¹,

Kim²,

Kim³

et al. 2013

Biomolecules and Therapeutics

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In this study, we investigated the effect of (–)-epigallocatechin-3-gallate (EGCG), a major component of green tea catechins from green tea leaves, on activities of cyclooxygenase (COX)-1 and thromboxane synthase (TXAS), thromboxane A2 (TXA2) production associated microsomal enzymes. EGCG inhibited COX-1 activity to 96.9%, and TXAS activity to 20% in platelet microsomal fraction having cytochrome c reductase (an endoplasmic reticulum marker enzyme) activity and expressing COX-1 (70 kDa) and TXAS (58 kDa) proteins. The inhibitory ratio of COX-1 to TXAS by EGCG was 4.8. These results mean that EGCG has a stronger selectivity in COX-1 inhibition than TXAS inhibition. In special, a nonsteroid anti-inflammatory drug aspirin, a COX-1 inhibitor, inhibited COX-1 activity by 11.3% at the same concentration (50 μM) as EGCG that inhibited COX-1 activity to 96.9% as compared with that of control. This suggests that EGCG has a stronger effect than that of aspirin on inhibition of COX-1 activity. Accordingly, we demonstrate that EGCG might be used as a crucial tool for a strong negative regulator of COX-1/TXA2 signaling pathway to inhibit thrombotic disease-associated platelet aggregation.

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“…As reported by Moncada and Vane (1979) [13] the smooth muscle cells are able to generate PGI 2 , and the arterial endothelial cells synthesize this factor three or ten times more than the venous endothelium. In the same way, Samokovlisky et al (1999) [14] have shown that the increase of cAMP in bovine aortic endothelial cells inhibits PGI 2 production, an effect that is suppressed by cAMP inhibition.…”

Section: Introductionmentioning

confidence: 82%

Vasodilatation induced by forskolin involves cyclic GMP production

Neto¹,

Lunardi²,

Rodrigues³

et al. 2011

JBPC

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Endothelium-derived relaxing factors contribute to smooth muscle relaxation. The aim of the present study was to investigate the contribution of nitric oxide (NO) produced in the endothelial cells to the vasodilatation stimulated with forskolin in rat aorta. Forskolin that directly activates adenylyl-cyclase, induced complete relaxation in phenylephrine-contracted aortas. Endothelium removal reduced the potency (pEC50) of forskolin without changes in the maximum effect (Emax). However, the inhibitor of endothelial NO-synthase (10 μM L- NG-Nitroarginine, L-NNA) reduced both Emax and pEC50 in intact endothelium aortic rings. L-NNA or L-NNA plus cyclooxygenase inhibitor indomethacin (10 μM) reduced both Emax and pEC50 of forskolin. Forskolin increased both the cytosolic Ca+2 concentration and the cytosolic NO concentration ([NO]c) in the endothelial cells. The PKA inhibitor KT5720 reduced the NO production activated by forskolin in the endothelial cells. The enhanced [NO]c in the endothelial cells increased cyclic guanosine-monophosphate (cGMP) in smooth muscle cells, which was abolished by L-NNA. Taken together, our results indicate that vasodilatation mediated by forskolin in rat aortic rings is potentiated by NO production in endothelial cells that increases the cGMP levels in the smooth muscle cells that along with cAMP contribute to the vasodilatation

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Differential regulation of cyclooxygenase isozymes by cAMP-elevating agents

Cited by 7 publications

References 34 publications

Prostaglandin H Synthase and Vascular Function

Prostaglandin H Synthase and Vascular Function

Inhibitory Effects of Epigallocatechin-3-Gallate on Microsomal Cyclooxygenase-1 Activity in Platelets

Vasodilatation induced by forskolin involves cyclic GMP production

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