Altered TP receptor function in isolated, perfused kidneys of nondiabetic and diabetic ApoE-deficient mice

Michel, Fabrice; Simonet, Serge; Vayssettes-Courchay, Christine; Bertin, Florence; Sansilvestri-Morel, Patricia; Bernhardt, Fabienne; Paysant, Jérôme; Silvestre, Jean‐Sébastien; Lévy, Bernard; Félétou, Michel; Verbeuren, Tony J.

doi:10.1152/ajprenal.00111.2007

Cited by 24 publications

(14 citation statements)

References 47 publications

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“…The samples were stored at Ϫ20°C, and TxB 2 was measured using a specific enzymatic immunoassay kit (Cayman Chemical) according to the manufacturer's instructions. The levels of TxB2 are expressed in picograms per milliliter (pg/ml) (33).…”

Section: Experimental Protocolmentioning

confidence: 99%

Involvement of neutral sphingomyelinase in the angiotensin II signaling pathway

Bautista-Pérez

Valle-Mondragón

Cano-Martı́nez

et al. 2015

American Journal of Physiology-Renal Physiology

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The possibility that angiotensin II (ANG II) exerts its effects through the activation of neutral sphingomyelinase (nSMase) has not been tested in kidneys. The results of the present study provide evidence for the activity and expression of nSMase in rat kidneys. In isolated perfused rat kidney, ANG II-induced renal vasoconstriction was inhibited by GW4869, an inhibitor of nSMase. We used nSMase for investigating the signal transduction downstream of ceramide. nSMase constricted the renal vasculature. An inhibitor of ceramidase (CDase), N-oleoylethanolamine (OEA), enhanced either ANG II-or nSMase-induced renal vasoconstriction. To demonstrate the interaction between the nSMase and cytosolic phospholipase A 2 (cPLA2) signal transduction pathways, we evaluated the response to nSMase in the presence and absence of inhibitors of arachidonic acid (AA) metabolism: arachidonyl trifluoromethyl ketone (AACOCF3), an inhibitor of cPLA2; 5,8,11,14-eicosatetraynoic acid (ETYA), an inhibitor of all AA pathways; indomethacin, an inhibitor of cyclooxygenase (COX); furegrelate, a thromboxane A 2 (TxA2)-synthase inhibitor; and SQ29548, a TxA 2-receptor antagonist. In these experiments, the nSMase-induced renal vasoconstriction decreased. ANG II or nSMase was associated with an increase in the release of thromboxane B2 (TxB2) in the renal perfusate of isolated perfused rat kidney. In addition, the coexpression of the ceramide with cPLA2, was found in the smooth muscle layer of intrarenal vessels. Our results suggest that ANG II stimulates ceramide formation via the activation of nSMase; thus ceramide may indirectly regulate vasoactive processes that modulate the activity of cPLA2 and the release of TxA2. renal vasoconstriction; angiotensin II; sphingomyelinase; phospholipase A2; cyclooxygenase; thromboxane A2 SPHINGOLIPIDS ARE A FAMILY of lipids that play essential roles as structural cell membrane components and also serve as substrates for enzymes that generate second messengers involved in cell signaling. Thus sphingolipids can be hydrolyzed by sphingomyelinases (SMases) (43). SMases are divided into three major classes, alkaline, acid, and neutral, according to the optimal pH for their activity, primary structure, and localization (15). Acid and alkaline SMases contribute to the hydrolysis of sphingomyelin in the luminal border of cells, in the extracellular space, or in the endosomal system, whereas neutral SMase (nSMase) functions in the inner leaflet of the plasma membrane (32). SMases cleave the phosphodiester linkage of sphingomyelin to produce phosphocholine and ceramide.

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Section: Experimental Protocolmentioning

confidence: 99%

Involvement of neutral sphingomyelinase in the angiotensin II signaling pathway

Bautista-Pérez

Valle-Mondragón

Cano-Martı́nez

et al. 2015

American Journal of Physiology-Renal Physiology

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“…Michel et al [24] found an increased responsiveness of TP receptors in diabetic apolipoprotein E-deficient mice. Terutroban inhibited vasoconstriction in response to ligands of TP receptors.…”

Section: Properties Of Terutroban a Tp Receptor Antagonistmentioning

confidence: 99%

TP Receptor Antagonism: A New Concept in Atherothrombosis and Stroke Prevention

Chamorro¹

2009

Cerebrovasc Dis

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Conventional antiplatelet agents such as aspirin, ticlopidine, and clopidogrel are currently used in the prevention of cardiovascular and cerebrovascular events. However, side effects such as bleeding complications and gastrointestinal disorders and, in some patients, resistance have made the development of new agents desirable. Recently, thromboxane receptors (thromboxane and prostaglandin endoperoxide PGG₂-PGH₂ receptors) called TP receptors have received increasing attention. These receptors are membrane-bound G-coupled receptors found not only on platelets but also on macrophages, monocytes, vascular endothelial cells, and smooth muscle cells. Antagonists of TP receptors have advantages over aspirin as they not only block the effect of thromboxane A₂ on platelets, but also inhibit other ligands such as prostaglandin endoperoxides and isoprostanes. Given the distribution of TP receptors in platelets, in circulating inflammatory cells, in the vascular wall and in atherosclerotic plaques, they also inhibit the effects of thromboxane A₂ over TP receptors on vascular cells or in the plaque. Terutroban (Triplion® or S18886), a new oral specific TP receptor antagonist, has, aside from being an antithrombotic agent, important vascular properties. It improves endothelial function and has an antiatherosclerotic effect. The potential therapeutic applications of terutroban in the prevention of atherothrombosis, particularly in the cerebrovascular and cardiovascular fields including stroke and coronary artery disease, are based on a number of convincing experimental animal and clinical studies. A large trial is currently comparing the efficacy and safety of terutroban versus aspirin in secondary prevention of cardiovascular events in patients who have suffered a stroke or transient ischemic attack (PERFORM Study).

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“…A role for TxA 2 in inflammatory bowel disease is also a possibility (Rampton and Collins, 1993). The vasoconstrictor activity of TP receptors may also be a factor in renal disease (Michel et al, 2008;Araujo and Welch, 2009). TxA 2 has also been advanced as a key regulator during Trypanosoma cruzi infection and may contribute to mortality and parasitism (Ashton et al, 2007).…”

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confidence: 99%