Dynorphin potentiation of [3H]CGP-39653 binding to rat brain membranes

Eur J Pharmacol. 1994 Dec 12;271(1):241-4. doi: 10.1016/0014-2999(94)90288-7.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Amino-5-phosphonovalerate / analogs & derivatives*
  • 2-Amino-5-phosphonovalerate / metabolism
  • Animals
  • Binding Sites / drug effects
  • Brain / drug effects
  • Brain / metabolism*
  • Dynorphins / pharmacology*
  • In Vitro Techniques
  • Kinetics
  • Ligands
  • Membranes / drug effects
  • Membranes / metabolism
  • Narcotics / pharmacology
  • Peptide Fragments / pharmacology
  • Rats
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*


  • Ligands
  • Narcotics
  • Peptide Fragments
  • Receptors, N-Methyl-D-Aspartate
  • CGP 39653
  • dynorphin (1-13)
  • Dynorphins
  • 2-Amino-5-phosphonovalerate