L. Kasakov, M. Nashar, E. Naydenova, L Vezenkov and M. Vlaskovska Pages 616 - 620 ( 5 )
Based on template hexapeptides Ac-Arg-Tyr-Tyr-Arg-Trp-Lys-NH2 and Ac-Arg-Tyr-Tyr-Arg-Ile-Lys-NH2 analogues and corresponding deacylated homologues were synthesized substituting ornithine, diaminobutanoic (Dab) and diaminopropanoic (Dap) acids for lysine at position 6. The aim was to investigate the effect of the newly synthesized compounds on the neurogenic contractions of isolated rat vas deferens. Ac-Arg-Tyr-Tyr-Arg-Trp-Lys-NH2 and its analogues manifested a strong inhibitory effect on the neurogenic contractions without effect on the muscle tone, which is characteristic effect of NOP receptor agonists. In contrast, Ac-Arg-Tyr-Tyr-Arg-Ile-Lys-NH2 and its analogs manifested a strong inhibitory effect on the muscle tone and negligible effect on the neurogenic contractions which is characteristic effect of NOP receptor antagonists. The most active were the peptides in which Dab or Dap is the substitute. The study reveals that substitution of Lys with shorter amino acids could increase agonist or antagonist activity of the peptide.
NOP receptor ligands, structure-activity relationship, rat vas deferens, neurogenic contraction
Institute of Neurobiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Street, bl. 23, 1113 Sofia, Bulgaria.