Interaction of histogranin and related peptides with [3H]dextromethorphan binding sites in rat brain.
Histogranin (HN) and related peptides were tested for their ability to modulate the binding of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, [3H]dextromethorphan ([3H]DM), to rat brain membranes. HN, [Ser1]HN and the C-terminal fragment HN-(6-15) (0.1 nM-1 microM) potentiated (up to 1.6-fold) the binding of [3H]DM (5 nM) whereas the N-terminal fragment HN-(1-10) had no effect. The potentiation of [3H]DM binding by [Ser1]HN was blocked by NMDA (100 microM) and the NMDA receptor antagonist, CPP (1 microM) but not by the sigma (sigma) receptor ligand, (+)-pentazocine (0.1 microM) and the phencyclidine (PCP) receptor ligand, TCP (1 microM). Equilibrium binding experiments in presence of TCP (1 microM) to block PCP receptors indicated that [Ser1]HN (1 microM) causes a significant increase in the binding capacity (Bmax) of [3H]DM (from 2.46 to 3.46 pmol/mg protein) but no change in the apparent dissociation constant (Kd of 428 nM as compared with 487 nM). The results indicate that HN and related peptides specifically enhance the number of [3H]DM binding sites associated to the NMDA receptor complex.
Dumont
M
M
Department of Pharmacology, Faculty of Medicine, University of Ottawa, Ont., Canada.
Prasad
J
J
Lemaire
S
S
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003915:Dextromethorphan / Q000493:pharmacokinetics*; D005998:Glycine / Q000378:metabolism; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D007700:Kinetics; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009479:Neuropeptides / Q000494:pharmacology*; D010879:Piperazines / Q000378:metabolism; D011506:Proteins / Q000494:pharmacology*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000378:metabolism*; D017478:Receptors, Phencyclidine / Q000187:drug effects / Q000378:metabolism; D017480:Receptors, sigma / Q000187:drug effects / Q000378:metabolism
D007457:Iodine Radioisotopes; D009479:Neuropeptides; D010879:Piperazines; D011506:Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D017478:Receptors, Phencyclidine; D017480:Receptors, sigma; C082312:histogranin; D003915:Dextromethorphan; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D005998:Glycine