histogranin and 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic-acid

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.

Topics: Animals; Brain; Dextromethorphan; Glycine; In Vitro Techniques; Iodine Radioisotopes; Kinetics; Membranes; Neuropeptides; Piperazines; Proteins; Rats; Receptors, N-Methyl-D-Aspartate; Receptors, Phencyclidine; Receptors, sigma