title: In vitro studies of the activity of newly sinthesized nociceptin / orphanin FQ receptor ligand analogues.
abstract: Based on template hexapeptides Ac-Arg-Tyr-Tyr-Arg-Trp-Lys-NH(2) and Ac-Arg-Tyr-Tyr-Arg-Ile-Lys-NH(2) 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-NH(2) 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-NH(2) 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.
authors.affiliation: Institute of Neurobiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.
authors.forename: L
authors.initials: L
authors.lastname: Kasakov
authors.forename: M
authors.initials: M
authors.lastname: Nashar
authors.forename: E
authors.initials: E
authors.lastname: Naydenova
authors.forename: L
authors.initials: L
authors.lastname: Vezenkov
authors.forename: M
authors.initials: M
authors.lastname: Vlaskovska
mesh_terms: D000818:Animals; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects; D018847:Opioid Peptides / Q000737:chemistry / Q000494:pharmacology*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000819:agonists*; D012044:Regression Analysis; D014649:Vas Deferens / Q000187:drug effects / Q000378:metabolism; D000094942:Nociceptin Receptor; D000097629:Nociceptin
chemical_list: D018847:Opioid Peptides; D010455:Peptides; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C000722285:Oprl1 protein, rat