Arginine Vasopressin Receptor 1A - Ligand Binding

Ligand Binding

In the N-terminal juxtamembrane segment of the AVPR1A, the glutamate residue at position 54 (E54) and the arginine residue at position 46 (R46) are critical for binding with AVP and AVP agonists, with E54 likely to interact with AVP and R46 to contribute to a conformational switch.

Competitors of Tyr-Phaa-specific binding to AVPR1A include:

• linear V1a antagonist phenylacetyl-D-Tyr(Et)-Phe-Gln-Asn-Lys-Pro-Arg-NH₂ (K_i = 1.2 ± 0.2 nM)
• linear V1a non-peptide antagonist SR 49059 (K_i = 1.3 ± 0.2 nM)
• AVP (K_i = 1.8 ± 0.4 nM)
• Linear V1a antagonist phenylacetyl-D-Tyr(Et)-Phe-Val-Asn-Lys-Pro-Tyr-NH₂ (Ki = 3.0 ± 0.5 nM)
• V2 antagonist d(CH₂)₅-AVP (K_i = 68 ± 17 nM)
• Oxytocin (K_i = 68 ± 17 nM)

Synthetic antagonists of AVPR1A include Relcovaptan and PF-184563

The AVPR1A is endocytosed by binding to beta arrestin, which dissociates rapidly from AVPR1A to allow it to return to the plasma membrane; however, upon activation, AVPR1A can heterodimerize with AVPR2 to increase beta-arrestin-mediated endocytosis (and intracellular accumulation) of AVPR1A, since AVPR2 is far less likely to dissociate from beta-arrestin.