Prostacyclin(PGI2) synthesis elicited by endothelin-1(ET-1) in rat aorta is mediated by a pertussis toxin-insensitive G protein via activation of phospholipase(PL) D but not PLC or PLA2

H. M. Wright, Kafait Malik

Research output: Contribution to journalArticle

Abstract

ET-1 stimulates PGI2 synthesis in rat aorta through an ETA receptor via influx of calcium and independently of protein kinasc C(Hypertension, 26. 1995, in press). This study was conducted to further characterize the signal transduction pathvvay(s) involved in the release of arachidonic acid(AA) for PGh synthesis in rat aortic rings. ET-1-increased PGl2 Synthesis(measurcd as immunorcactive 6-keto-PGFlα) was not altered by pertussis toxin ET 1- enhanced PLC activity, indicated by increased mositol phosphate production, was prevented by a PLC inhibitor, U-73122. However, ET-1induccd PGIo production was not altered by U-73122 ET-1-induced PGN synthesis was not affected by a PLA2 inhibitor, DEDA. Furthermore, ET-1 failed to stimulate PLA2 activity measured in the cytosol, utilizing phosphatidylcholinc,L-a-l-palmitoyl2-arachidonyl-14C as u substrate. On the other hand, the adrcncrgic agonist norepincphnnc did enhance PLA2 activity. Reported inhibitors of PLD(lvorlmannin), phosphatidatc phosphohydrolase(propranolol), and diacylglycerol hpase(RHC-80267) uil attenuated ET-1-induced PGI2 synthesis These data suggest a novel pathway whereby ET-1, acting through a pertussis toxin-insensitive G protein, activates PLD, generating phosphatidic acid, which, alter being converted to diacylglycerol, is acted upon by a lipase to release AA for PGI2 synthesis.

Original languageEnglish (US)
JournalFASEB Journal
Volume10
Issue number3
StatePublished - Dec 1 1996

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Phospholipase D
Pertussis Toxin
Endothelin-1
Epoprostenol
Programmable logic controllers
GTP-Binding Proteins
Aorta
Rats
Chemical activation
Diglycerides
Arachidonic Acid
Signal transduction
Phosphatidic Acids
Protein C
Lipase
Phosphoric Monoester Hydrolases
Propranolol
Cytosol
Signal Transduction
Phosphates

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

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title = "Prostacyclin(PGI2) synthesis elicited by endothelin-1(ET-1) in rat aorta is mediated by a pertussis toxin-insensitive G protein via activation of phospholipase(PL) D but not PLC or PLA2",
abstract = "ET-1 stimulates PGI2 synthesis in rat aorta through an ETA receptor via influx of calcium and independently of protein kinasc C(Hypertension, 26. 1995, in press). This study was conducted to further characterize the signal transduction pathvvay(s) involved in the release of arachidonic acid(AA) for PGh synthesis in rat aortic rings. ET-1-increased PGl2 Synthesis(measurcd as immunorcactive 6-keto-PGFlα) was not altered by pertussis toxin ET 1- enhanced PLC activity, indicated by increased mositol phosphate production, was prevented by a PLC inhibitor, U-73122. However, ET-1induccd PGIo production was not altered by U-73122 ET-1-induced PGN synthesis was not affected by a PLA2 inhibitor, DEDA. Furthermore, ET-1 failed to stimulate PLA2 activity measured in the cytosol, utilizing phosphatidylcholinc,L-a-l-palmitoyl2-arachidonyl-14C as u substrate. On the other hand, the adrcncrgic agonist norepincphnnc did enhance PLA2 activity. Reported inhibitors of PLD(lvorlmannin), phosphatidatc phosphohydrolase(propranolol), and diacylglycerol hpase(RHC-80267) uil attenuated ET-1-induced PGI2 synthesis These data suggest a novel pathway whereby ET-1, acting through a pertussis toxin-insensitive G protein, activates PLD, generating phosphatidic acid, which, alter being converted to diacylglycerol, is acted upon by a lipase to release AA for PGI2 synthesis.",
author = "Wright, {H. M.} and Kafait Malik",
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T1 - Prostacyclin(PGI2) synthesis elicited by endothelin-1(ET-1) in rat aorta is mediated by a pertussis toxin-insensitive G protein via activation of phospholipase(PL) D but not PLC or PLA2

AU - Wright, H. M.

AU - Malik, Kafait

PY - 1996/12/1

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N2 - ET-1 stimulates PGI2 synthesis in rat aorta through an ETA receptor via influx of calcium and independently of protein kinasc C(Hypertension, 26. 1995, in press). This study was conducted to further characterize the signal transduction pathvvay(s) involved in the release of arachidonic acid(AA) for PGh synthesis in rat aortic rings. ET-1-increased PGl2 Synthesis(measurcd as immunorcactive 6-keto-PGFlα) was not altered by pertussis toxin ET 1- enhanced PLC activity, indicated by increased mositol phosphate production, was prevented by a PLC inhibitor, U-73122. However, ET-1induccd PGIo production was not altered by U-73122 ET-1-induced PGN synthesis was not affected by a PLA2 inhibitor, DEDA. Furthermore, ET-1 failed to stimulate PLA2 activity measured in the cytosol, utilizing phosphatidylcholinc,L-a-l-palmitoyl2-arachidonyl-14C as u substrate. On the other hand, the adrcncrgic agonist norepincphnnc did enhance PLA2 activity. Reported inhibitors of PLD(lvorlmannin), phosphatidatc phosphohydrolase(propranolol), and diacylglycerol hpase(RHC-80267) uil attenuated ET-1-induced PGI2 synthesis These data suggest a novel pathway whereby ET-1, acting through a pertussis toxin-insensitive G protein, activates PLD, generating phosphatidic acid, which, alter being converted to diacylglycerol, is acted upon by a lipase to release AA for PGI2 synthesis.

AB - ET-1 stimulates PGI2 synthesis in rat aorta through an ETA receptor via influx of calcium and independently of protein kinasc C(Hypertension, 26. 1995, in press). This study was conducted to further characterize the signal transduction pathvvay(s) involved in the release of arachidonic acid(AA) for PGh synthesis in rat aortic rings. ET-1-increased PGl2 Synthesis(measurcd as immunorcactive 6-keto-PGFlα) was not altered by pertussis toxin ET 1- enhanced PLC activity, indicated by increased mositol phosphate production, was prevented by a PLC inhibitor, U-73122. However, ET-1induccd PGIo production was not altered by U-73122 ET-1-induced PGN synthesis was not affected by a PLA2 inhibitor, DEDA. Furthermore, ET-1 failed to stimulate PLA2 activity measured in the cytosol, utilizing phosphatidylcholinc,L-a-l-palmitoyl2-arachidonyl-14C as u substrate. On the other hand, the adrcncrgic agonist norepincphnnc did enhance PLA2 activity. Reported inhibitors of PLD(lvorlmannin), phosphatidatc phosphohydrolase(propranolol), and diacylglycerol hpase(RHC-80267) uil attenuated ET-1-induced PGI2 synthesis These data suggest a novel pathway whereby ET-1, acting through a pertussis toxin-insensitive G protein, activates PLD, generating phosphatidic acid, which, alter being converted to diacylglycerol, is acted upon by a lipase to release AA for PGI2 synthesis.

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