Signal transduction mechanisms involved in angiotensin-(1-7)-stimulated arachidonic acid release and prostanoid synthesis in rabbit aortic smooth muscle cells

Mubarack M. Muthalif, Ibrahim F. Benter, Mohammad R. Uddin, Jason L. Harper, Kafait Malik

Research output: Contribution to journalArticle

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Abstract

This study investigated the signal transduction mechanisms of angiotensin-(1-7) [Ang-(1-7)]- and Ang II-stimulated arachidonic acid (AA) release for prostaglandin (PG) production in rabbit aortic vascular smooth muscle cells. Ang II and Ang-(1-7) enhanced AA release in cells prelabeled with [3H]AA. However, -keto-PGF(1α) synthesis produced by Ang II was much less than that caused by Ang-(1-7). In the presence of the lipoxygenase inhibitor baicalein, Ang II enhanced production of 6-keto-PGF(1α) to a greater degree than Ang-(1-7). Angiotensin type (AT)1 receptor antagonist DUP-753 inhibited only Ang II-induced [3H]AA release, whereas the AT2 receptor antagonist PD-123319 inhibited both Ang II- and Ang-(1-7)-induced [3H]AA released. Ang-(1-7) receptor antagonist D-Ala7-Ang-(1-7) inhibited the effect of Ang-(1-7), but not of Ang II. In cells transiently transfected with cytosolic phospholipase A2 (cPLA2), mitogen-activated protein (MAP) kinase or Ca++-/calmodulin-dependent protein (CAM) kinase II antisense oligonucleotides, Ang-(1-7)- and Ang II-induced [3H]AA release was attenuated. The CaM kinase II inhibitor KN-93 and the MAP kinase kinase inhibitor PD-98059 attenuated both Ang-(1-7)-and Ang II-induced cPLA2 activity and [3H]AA release. Ang-(1-7) and Ang II also increased CaM kinase II and MAP kinase activities. Although KN-93 attenuated MAP kinase activity, PD-98059 did not affect CaM kinase II activity. Both Ang II and Ang-(1-7) caused translocation of cytosolic PLA2 to the nuclear envelope. These data show that Ang-(1-7) and Ang II stimulate AA release and prostacyclin synthesis via activation of distinct types of AT receptors. Both peptides appear to stimulate CaM kinase II, which in turn, via MAP kinase activation, enhances cPLA2 activity and release of AA for PG synthesis.

Original languageEnglish (US)
Pages (from-to)388-398
Number of pages11
JournalJournal of Pharmacology and Experimental Therapeutics
Volume284
Issue number1
StatePublished - Jan 1 1998

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Arachidonic Acid
Prostaglandins
Smooth Muscle Myocytes
Signal Transduction
Rabbits
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Cytosolic Phospholipases A2
Mitogen-Activated Protein Kinases
Prostaglandins F
angiotensin I (1-7)
Angiotensin II Type 1 Receptor Blockers
Lipoxygenase Inhibitors
Angiotensin Receptors
Antisense Oligonucleotides
Mitogen-Activated Protein Kinase Kinases
Nuclear Envelope
Epoprostenol
Vascular Smooth Muscle

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

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Signal transduction mechanisms involved in angiotensin-(1-7)-stimulated arachidonic acid release and prostanoid synthesis in rabbit aortic smooth muscle cells. / Muthalif, Mubarack M.; Benter, Ibrahim F.; Uddin, Mohammad R.; Harper, Jason L.; Malik, Kafait.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 284, No. 1, 01.01.1998, p. 388-398.

Research output: Contribution to journalArticle

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