RT Journal Article
SR Electronic
T1 Angiotensin II-Induced Cyclooxygenase 2 Expression in Rat Aorta Vascular Smooth Muscle Cells Does Not Require Heterotrimeric G Protein Activation
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 118
OP 124
DO 10.1124/jpet.109.151829
VO 330
IS 1
A1 Thomas A. Morinelli
A1 Ryan T. Kendall
A1 Louis M. Luttrell
A1 Linda P. Walker
A1 Michael E. Ullian
YR 2009
UL http://jpet.aspetjournals.org/content/330/1/118.abstract
AB Angiotensin II (AngII) initiates cellular effects via its G protein-coupled angiotensin 1 (AT1) receptor (AT1R). Previously, we showed that AngII-induced expression of the prostanoid-producing enzyme cyclooxygenase 2 (COX-2) was dependent upon nuclear trafficking of activated AT1R. In the present study, mastoparan (an activator of G proteins), suramin (an inhibitor of G proteins), 1-[6-[[17β-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione (U73122; a specific inhibitor of phospholipase C), and sarcosine1-Ile4-Ile8-AngII (SII-AngII; a G protein-independent AT1R agonist) were used to determine the involvement of G proteins and AT1AR trafficking in AngII-stimulated COX-2 protein expression in human embryonic kidney-293 cells stably expressing AT1A/green fluorescent protein receptors and cultured vascular smooth muscle cells, respectively. Mastoparan alone stimulated release of intracellular calcium and increased COX-2 expression. Preincubation with mastoparan inhibited AngII-induced calcium signaling without altering AngII-induced AT1AR trafficking, p42/44 extracellular signal-regulated kinase (ERK) activation, or COX-2 expression. Suramin or U73122 had no significant effect on their own; they did not inhibit AngII-induced AT1AR trafficking, p42/44 ERK activation, or COX-2 expression; but they did inhibit AngII-induced calcium responses. SII-AngII stimulated AT1AR trafficking and increased COX-2 protein expression without activating intracellular calcium release. These data suggest that G protein activation results in increased COX-2 protein expression, but AngII-induced COX-2 expression seems to occur independently of G protein activation.