Implication of multiple signaling pathways in the regulation of angiotensin II induced enhanced expression of Giα proteins in vascular smooth muscle cells.
We have previously shown that A10 vascular smooth muscle cells (VSMC) exposed to angiotensin II (Ang II) exhibited overexpression of Giα proteins. In the present study, we examined the involvement of different signaling pathways in regulating Ang II induced enhanced expression of Giα proteins in VSMC by using pharmacological inhibitors. Ang II induced increased expression of Giα proteins in A10 VSMC was markedly attenuated by actinomycin D, losartan (an AT(1) receptor antagonist), dibutyryl cAMP, phospholipase C (PLC) inhibitor U73122, protein kinase C (PKC) inhibitors staurosporine and GP109203X, but not by PD123319 (an AT(2) receptor antagonist). In addition, BAPTA-AM and TMB-8 (chelators of intracellular Ca(2+)); and nifedipine (a blocker of L-type Ca(2+) channels) significantly inhibited Ang II induced enhanced expression of Giα proteins. On the other hand, extracellular Ca(2+) chelation using EGTA did not affect the Ang II evoked enhanced levels of Giα proteins. Furthermore, pretreatment of A10 VSMC with calmidazolium (an inhibitor of calmodulin), or KN93 (an inhibitor of CaM kinase), or genistein (an inhibitor of protein tyrosine kinase, PTK), also attenuated the increased levels of Giα proteins induced by Ang II. These results suggest that Ang II induced enhanced expression of Giα proteins may be regulated by different signaling pathways through AT(1) receptors in A10 VSMC.
Department of Physiology, Faculty of Medicine, University of Montreal, QC, Canada.
Yuan
Y
Li
Madhu B
MB
Anand-Srivastava
D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D057912:Angiotensin II Type 2 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002614:Chelating Agents / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004347:Drug Interactions; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000096:biosynthesis*; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D019833:Genistein / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D002614:Chelating Agents; D004963:Estrenes; D007093:Imidazoles; D019384:Nucleic Acid Synthesis Inhibitors; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011760:Pyrrolidinones; D000804:Angiotensin II; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C073402:PD 123319; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D003609:Dactinomycin; D004533:Egtazic Acid; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D003994:Bucladesine; D019833:Genistein; D010738:Type C Phospholipases; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D019808:Losartan; D002118:Calcium