Résumé
In the present study we aimed to investigate the effects of shortening of nociceptin side-chain in position 9, replacing in the peptide molecule Lys(9) by diaminobutanoic acid (Dab), diaminopropanoic acid (Dap) or structural analogue of arginine canavanine (Cav). The experiments were carried out in vitro on electrically-stimulated smooth-muscle preparations from rat vas deferens. Shortening of the side-chain in position 9 with 2 CH2- (Dab) or with 3 CH2-groups (Dap) decreased the affinity for OP4 receptors, as well as the efficacy of the newly-synthesized peptides, compared to the native compound. The substitution of Lys(9/13) by Cav in the nociceptin molecule affects the selectivity of the peptide action. The new peptides could activate both the OP4 receptors and naloxone-sensitive opioid receptors. The substitution in position 9 reflects in a stronger effect on the biological activity showing that the positively charged groups of Lys(9) are more important for the receptor occupation than those in position 13.