title: A potent and long-acting NK-1 selective agonist.
abstract: In rats anesthetized with urethane, substance P exerts a short-lasting hypotensive effect and stimulates salivary secretion. These effects are significantly increased and prolonged by 5 to 10 times, when substance P is administered in the presence of a mixture of peptidase inhibitors (captopril, thiorphan and phosphoramidon). Ac[Arg6,Sar9,Met(O2)11]SP(6-11), a selective NK-1 receptor agonist, shows high potency and prolonged hypotensive and sialologic effects. The effects of the NK-1 selective hexapeptide are comparable to those of substance P tested in the presence of peptidase inhibitors and are not modified by peptidase inhibitors. Ac[Arg6,Sar9,Met(O2)11]SP (6-11) is proposed as a useful tool for studying the roles and functions of NK-1 receptors in vivo, because of its stability, potency and selectivity.
authors.affiliation: Department of Pharmacology, Université de Sherbrooke, Québec.
authors.forename: N
authors.initials: N
authors.lastname: Rouissi
authors.forename: D
authors.initials: D
authors.lastname: Jukic
authors.forename: P
authors.initials: P
authors.lastname: D'Orléans-Juste
authors.forename: D
authors.initials: D
authors.lastname: Regoli
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D010446:Peptide Fragments / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D018039:Receptors, Tachykinin; D012472:Salivation / Q000187:drug effects; D013373:Substance P / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors
chemical_list: D010446:Peptide Fragments; D011480:Protease Inhibitors; D017981:Receptors, Neurotransmitter; D018039:Receptors, Tachykinin; C080168:substance P (6-11), Ac(Arg(6)-Sar(9)-Met(O2)(11))-; D013373:Substance P