title: Heterogeneity of [3H]neurotensin bindings: studies with dynorphin, L-156,903 and levocabastine.
abstract: The binding of [3H]neurotensin (NT) to membranes from rat forebrain was complex, exhibiting 'high' affinity (Kd approximately 0.5 nM) and 'low' affinity (Kd approximately 5.0 nM) binding components. Dynorphin A(1-13) (DYN A(1-13] and L-156,903 (N-oxo-3-(10H-phenothiazine-10-yl)propyl-1- arginyl-1-prolyl-1-phenylalanine) potently inhibited [3H]NT binding to brain with shallow biphasic competition curves. Saturation binding studies conducted in the presence or absence of DYN A(1-13) or L-156,903 indicated that these compounds, like levocabastine, exhibited substantial selectivity for 'low' affinity NT site. Structure-activity studies indicated rigid structural requirements for the NT binding activity of DYN A(1-13) and L-156,903. In contrast to the results using brain tissue, DYN A(1-13), L-156,903 and levocabastine were very weak or inactive to inhibit [3H]NT binding to rat uterus. These studies further characterize the heterogeneity of [3H]NT binding in vitro and demonstrate clear tissue differences in binding within a given species.
authors.affiliation: Department of Microbial Pharmacometrics, Merck Sharp and Dohme Research Laboratories, West Point, PA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Pettibone
authors.forename: J A
authors.initials: JA
authors.lastname: Totaro
authors.forename: E
authors.initials: E
authors.lastname: Harris
authors.forename: F M
authors.initials: FM
authors.lastname: Robinson
mesh_terms: D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D004399:Dynorphins / Q000378:metabolism*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009496:Neurotensin / Q000378:metabolism*; D009842:Oligopeptides / Q000378:metabolism*; D010640:Phenothiazines / Q000378:metabolism*; D010880:Piperidines / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D009842:Oligopeptides; D010640:Phenothiazines; D010880:Piperidines; C058578:L 156903; D009496:Neurotensin; D004399:Dynorphins; C047340:levocabastine