A limited or a transient AT1R internalization induced by two discriminating agonists result in distinct downstream AT1R signaling: ERK1/2 and Akt/PKB

Agonist-induced AT1R Internalization, results from sequestration of the agonist-receptor complex into “clathrin vesicles”, depending on the internalization proteins: β-arrestin, clathrin. In this regard, we have shown that a 15,000 kDa polymer of Ang II (Ang II-POL) at maximal concentration, upon a sustained action on the AT1R of rat coronary endothelial luminal membrane (CELM) produced: a sustained inotropic effect, a lack of endothelial AT1R internalization, enhanced membranal recruitment of β-arrestin1/2, without clathrin recruitment a lack of clathrin-vesicles formation. In contrast, the monomer Ang II (1 kDa) inotropic effects shows desensitization, paralleled by endothelial AT1R internalization, and the well-known gradual membranal recruitment of the internalization proteins β-arrestin1/2 and clathrin. These results clearly show that Ang II and Ang II-POL distinctly activate AT1R as reflected by their different recruitment ways of the internalization proteins, which likely result in distinct downstream AT1R signaling: ERK1/2 and Akt/PKB phosphorylation. We studied this canonical signaling pathways triggered by AT1R activation, with both agonists.

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