title: Dynorphin potentiation of [3H]CGP-39653 binding to rat brain membranes.
abstract: Dynorphin A-(1-13) and related peptide fragments were tested for their ability to modulate the binding of the competitive NMDA receptor antagonist, [3H]2-amino-4-propyl-5-phosphono-3-pentanoic acid ([3H]CGP-39653), to rat brain membranes. Dynorphin A-(1-13) produced a dose-dependent (1 nM to 10 microM) potentiation of [3H]CGP-39653 binding. The potentiation was insensitive to the kappa-opioid receptor antagonist norbinaltorphimine and it was also observed with the non-opioid peptides dynorphin A-(2-13) and dynorphin A-(6-10). Among various compounds which interact with distinct sites on the NMDA receptor complex, glycine (Gly; 1 microM) and the Gly receptor antagonist, (+/-)-3-amino-1-hydroxy-2-pyrrolidone ((+/-)-HA-966; 10 microM), blocked the dynorphin A-(1-13) induced potentiation of [3H]CGP-39653 binding. In equilibrium binding experiments, dynorphin A-(1-13) (10 microM) caused a significant increase in the binding capacity (Bmax) of [3H]CGP-39653 (from 111 to 306 fmol/mg protein) but not change in the apparent dissociation constant (Kd of 8.5 nM as compared with 8.7 nM in the absence of the peptide). The results indicate that dynorphin A and related peptides modify the expression of [3H]CGP-39653 binding sites consecutive to a non-opioid interaction with the NMDA receptor complex.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Ottawa, Ontario, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Dumont
authors.forename: S
authors.initials: S
authors.lastname: Lemaire
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004399:Dynorphins / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008024:Ligands; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009294:Narcotics / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
chemical_list: D008024:Ligands; D009294:Narcotics; D010446:Peptide Fragments; D016194:Receptors, N-Methyl-D-Aspartate; C069052:CGP 39653; C026843:dynorphin (1-13); D004399:Dynorphins; D015763:2-Amino-5-phosphonovalerate