par Gourlet, Philippe ;Vandermeers-Piret, Marie-Claire ;Rathe, Jean ;De Neef, Philippe ;Cnudde, Johnny;Robberecht, Patrick ;Waelbroeck, Magali
Référence European journal of pharmacology, 348, 1, page (95-99)
Publication Publié, 1998-05
Référence European journal of pharmacology, 348, 1, page (95-99)
Publication Publié, 1998-05
Article révisé par les pairs
Résumé : | Secretin and growth hormone releasing factor (GRF) have a weak affinity for VIP (vasoactive intestinal peptide)/PACAP (pituitary adenylate cyclase activating polypeptide) receptors, but discriminate between VIP1/PACAP and VIP2/PACAP receptors. This previously allowed us to develop modified secretin and GRF derivatives as high affinity and highly selective VIP1/PACAP receptor ligands. We tested the hypothesis that the presence of a Gin residue at position 24 and a Leu residue at position 22 was responsible for their VIP1/PACAP receptor selectivity. [Gln24]VIP was not different from VIP but [Leu22]VIP had a 100-fold lower affinity for VIP2/PACAP receptors as compared to VIP1/PACAP receptors. The substitution of Tyr22 by Phe22 in VIP had no significant effect on the recognition of both receptors but [Ala22]VIP had a reduced affinity for the VIP2/PACAP receptor. This indicated that an aromatic residue at position 22 of VIP was required for a high affinity for the VIP2/PACAP receptor but not for the VIP1/PACAP receptor. |