S-(+)-PD 123177 trifluoroacetate salt hydrate

S-(+)-PD 123177 is selective AT2 angiotensin receptor antagonist. The angiotensin AT2 receptor is an atypical seven transmembrane domain receptor that is coupled to activation of tyrosine phosphatase and inhibition of MAP kinase, and does not undergo agonist-induced internalization. An investigation of the occurrence and nature of AT2 receptor phosphorylation revealed that phorbol ester-induced activation of protein kinase C (PKC) in HA-AT2 receptor-expressing COS-7 cells caused rapid and specific phosphorylation of a single residue (Ser³⁵⁴) located in the cytoplasmic tail of the receptor. Agonist activation of AT2 receptors by angiotensin II (Ang II) also caused rapid PKC-dependent phosphorylation of Ser^{354 t}hat was prevented by the AT2 antagonist, S-(+)-PD 123177, and by inhibitors of PKC. In cells coexpressing AT1 and AT2 receptors, Ang II-induced phosphorylation of the AT2 receptor was reduced by S-(+)-PD 123177 and abolished by treatment with both antagonists or with PKC inhibitors. These findings indicate that the AT2 receptor is rapidly phosphorylated via PKC during homologous activation by Ang II, and also undergoes heterologous PKC-dependent phosphorylation during activation of the AT1 receptor.

Selective AT₂ angiotensin receptor antagonist.

This compound is featured on the Angiotensin Receptors page of the Handbook of Receptor Classification and Signal Transduction. To browse other handbook pages, click here.