The highly selective CRF2 receptor antagonist K41498 binds to presynaptic CRF2 receptors in rat brain

Abstract

1 Novel analogues of antisauvagine-30 (aSvg-30), a selective antagonist for CRF2 receptors, have been synthesized and characterized in vitro and in vivo. 2 The analogues were tested for their ability to compete for [125I-Tyr0]Svg binding and to inhibit Svg-stimulated adenylate cyclase activity in human embryonic kidney (HEK) 293 cells, permanently transfected with cDNA coding for the human CRFi (hCRF1), hCRF2α and hCRF2β receptor. One analogue [D-Phe11, His12, Nle17]Svg(11-40), named K41498, showed high affinity binding to hCRF2agr (Ki=0.66±0.03 nm) and hCRF2β (Ki=0.62±0.01 nm) but not the hCRF1 receptor (ki=425+50 nM) and decreased Svg-stimulated cAMP accumulation in hCRF2 expressing cells...