title: 125I-BH[Sar9, Met(O2)11]-SP, a new selective ligand for the NK-1 receptor in the central nervous system.
abstract: The selective agonist [Sar9,Met(O2)11]-SP was radioiodinated with 125I-Bolton Hunter in order to study its binding to rat brain membranes and for further comparison with 125I-BH.SP. Specific binding of 125I-BH[Sar9,Met(O2)11]-SP was temperature-dependent, saturable and reversible. In brain homogenates, 125I-BH[Sar9,Met(O2)11]-SP interacted with a single class of high affinity (kd = 1.0 nM) non-interacting binding sites (Bmax of 15 fmol/mg protein). In the central nervous system, 125I-BH-[Sar9,Met(O2)11]-SP apparently labeled the same number of binding sites as 125I-BH.SP (19 fmol/mg proteins). Competition studies with tachykinins, neurokinins and selective neurokinin agonists indicated that the pharmacological profile of the site labeled by 125I-BH[Sar9,Met(O2)11]-SP is identical with that of NK-1 receptors. In dose-displacement studies made with radiolabeled SP and [Sar9,Met(O2)11)]-SP, an excellent correlation (r = 0.96) was found for the Ki values of the different compounds tested; these findings suggest that both radioligands recognize the same receptor in rat brain. The affinity (Ki) of various neurokinin-related peptides for the brain site were compared with their biological activities on various isolated organs (dog carotid artery, guinea-pig ileum, rat portal vein). NK-1 binding sites characterized in rat brain homogenates appear to be identical with those present on the dog carotid artery, a preparation known to possess exclusively the NK-1 receptor type.
authors.affiliation: Department of Pharmacology, Medical School, University of Sherbrooke, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Tousignant
authors.forename: G
authors.initials: G
authors.lastname: Guillemette
authors.forename: G
authors.initials: G
authors.lastname: Drapeau
authors.forename: S
authors.initials: S
authors.lastname: Télémaque
authors.forename: S
authors.initials: S
authors.lastname: Dion
authors.forename: D
authors.initials: D
authors.lastname: Regoli
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D001681:Biological Assay; D001921:Brain / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D007700:Kinetics; D008024:Ligands; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D018039:Receptors, Tachykinin; D013329:Structure-Activity Relationship; D013373:Substance P / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D015320:Tachykinins / Q000378:metabolism / Q000494:pharmacology
chemical_list: D008024:Ligands; D017981:Receptors, Neurotransmitter; D018039:Receptors, Tachykinin; D015320:Tachykinins; C062618:substance P, Sar(9)-Met(O2)(11)-; D013373:Substance P