Clathrin-dependent internalization of the angiotensin II AT₁A receptor links receptor internalization to COX-2 protein expression in rat aortic vascular smooth muscle cells.

The major effects of Angiotensin II (AngII) in vascular tissue are mediated by AngII AT1A receptor activation. Certain effects initiated by AT1A receptor activation require receptor internalization. In rat aortic vascular smooth muscle cells (RASMC), AngII stimulates cyclooxygenase 2 protein expression.

Angiotensin II activates NF-κB through AT1A receptor recruitment of β-arrestin in cultured rat vascular smooth muscle cells.

Activation of the angiotensin type 1A receptor (AT1AR) in rat aorta vascular smooth muscle cells (RASMC) results in increased synthesis of the proinflammatory enzyme cyclooxygenase-2 (COX-2). We previously showed that nuclear localization of internalized AT1AR results in activation of transcription of the gene for COX-2, i.e.

Angiotensin II-induced cyclooxygenase 2 expression in rat aorta vascular smooth muscle cells does not require heterotrimeric G protein activation.

Angiotensin II (AngII) initiates cellular effects via its G protein-coupled angiotensin 1 (AT(1)) receptor (AT(1)R). Previously, we showed that AngII-induced expression of the prostanoid-producing enzyme cyclooxygenase 2 (COX-2) was dependent upon nuclear trafficking of activated AT(1)R. In the present study, mastoparan (an activator of G proteins), suramin (an inhibitor of G proteins), 1-[6-[[17beta-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione (U73122; a specific inhibitor of phospholipase C), and sarcosine(1)-Ile(4)-Ile(8)-AngII (SII-AngII; a G protein-independent AT(1)R agonist) were used to determine the involvement of G proteins and AT(1A)R trafficking in AngII-stimulated COX-2 protein expression in human embryonic kidney-293 cells stably expressing AT(1A)/green fluorescent protein receptors and cultured vascular smooth muscle cells, respectively.

Thiol antioxidants regulate angiotensin II AT1 and arginine vasopressin V1 receptor functions differently in vascular smooth muscle cells.

Background: We compared the effects of the sulfhydryl-containing (thiol) antioxidant dithiothreitol (DTT), which disrupts disulfide bonds, on cell signaling through angiotensin II (AngII) Type 1 receptors (AT1Rs) and arginine vasopressin (AVP) V1 receptors (V1Rs). The AT1R contains two extracellular disulfides bonds but its ligand contains none, whereas the V1R contains no extracellular disufides bonds but its ligand contains 1.

Methods: We measured radioligand binding, intracellular calcium responses, and extracellular signal-regulated kinase phosphorylation in cultured rat aortic vascular smooth muscle cells and alterations in urine osmolality in intact rats.

COX-2 expression stimulated by Angiotensin II depends upon AT1 receptor internalization in vascular smooth muscle cells.

Previously, we demonstrated that nuclear localization of the Angiotensin II AT1A receptor was associated with the activation of transcription for the COX-2 gene, PTGS-2. The hypothesis of the present study is that AT1AR internalization from the plasma membrane is a first step in the nuclear localization of the endogenous AT1AR of rat aortic vascular smooth muscle cells and the resultant increase of COX-2 protein expression. Angiotensin II produced both a time- and concentration-dependent increase in COX-2 protein expression in these cells.

Genetic variation in cyclooxygenase 1: effects on response to aspirin.

Background: A critical clinical application of the Human Genome Project is to identify functional variation in genes related to disease or responses to xenobiotics. This study moved toward that goal by combining polymorphism detection with functional assays for the therapeutic target gene cyclooxygenase 1 (COX-1). Cyclooxygenase 1 (prostaglandin endoperoxide G/H synthase [PTGS1]) catalyzes the metabolism of arachidonic acid to prostaglandin H(2), which is subsequently metabolized to thromboxane A(2).