TY - JOUR T1 - Stimulatory and Inhibitory Properties of Aminoglycoside Antibiotics at <em>N-</em>Methyl-<span class="sc">d</span>-Aspartate Receptors JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1026 LP - 1033 VL - 290 IS - 3 AU - Takashi Masuko AU - Tomoko Kuno AU - Keiko Kashiwagi AU - Tadashi Kusama AU - Keith Williams AU - Kazuei Igarashi Y1 - 1999/09/01 UR - http://jpet.aspetjournals.org/content/290/3/1026.abstract N2 - The effects of aminoglycoside antibiotics onN-methyl-d-aspartate (NMDA) receptors were studied using voltage-clamp recording of recombinant NMDA receptors expressed in Xenopus oocytes. A number of aminoglycosides were found to potentiate macroscopic currents at heteromeric NR1a/NR2B receptors, but not at NR1a/NR2A, NR1a/NR2C, NR1a/NR2D, or NR1b/NR2B receptors. The degree of potentiation had a rank order neomycin B &gt; paromomycin &gt; gentamicin C &gt; geneticin &gt; kanamycin A &gt; streptomycin. Potentiation was not seen with kasugamycin and spectinomycin. The degree of stimulation paralleled the number of the amino groups in the aminoglycosides. The stimulatory effects of aminoglycosides were more pronounced at subsaturating concentrations of glycine and at acidic pH, similar to the stimulatory effects of spermine. We measured the effects of aminoglycosides at mutant NMDA receptors to determine which amino acid residues in NMDA receptor subunits are involved in stimulation. Mutations that reduced or abolished spermine stimulation also reduced stimulation by aminoglycosides. Several aminoglycosides produced a weak voltage-dependent block of NMDA receptors, but the degree of inhibition did not appear to correlate with the number of amino groups in the molecule. The results suggest that aminoglycosides having more than three amino groups have stimulatory effects that are mediated through the spermine-binding site on NMDA receptors. The American Society for Pharmacology and Experimental Therapeutics ER -