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Stimulatory and inhibitory properties of aminoglycoside antibiotics at N-methyl-D-aspartate receptors.
J Pharmacol Exp Ther. 1999 Sep; 290(3):1026-33.JP

Abstract

The effects of aminoglycoside antibiotics on N-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 > paromomycin > gentamicin C > geneticin > kanamycin A > 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.

Authors+Show Affiliations

Faculty of Pharmaceutical Sciences, Chiba University, Chiba, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10454474

Citation

Masuko, T, et al. "Stimulatory and Inhibitory Properties of Aminoglycoside Antibiotics at N-methyl-D-aspartate Receptors." The Journal of Pharmacology and Experimental Therapeutics, vol. 290, no. 3, 1999, pp. 1026-33.
Masuko T, Kuno T, Kashiwagi K, et al. Stimulatory and inhibitory properties of aminoglycoside antibiotics at N-methyl-D-aspartate receptors. J Pharmacol Exp Ther. 1999;290(3):1026-33.
Masuko, T., Kuno, T., Kashiwagi, K., Kusama, T., Williams, K., & Igarashi, K. (1999). Stimulatory and inhibitory properties of aminoglycoside antibiotics at N-methyl-D-aspartate receptors. The Journal of Pharmacology and Experimental Therapeutics, 290(3), 1026-33.
Masuko T, et al. Stimulatory and Inhibitory Properties of Aminoglycoside Antibiotics at N-methyl-D-aspartate Receptors. J Pharmacol Exp Ther. 1999;290(3):1026-33. PubMed PMID: 10454474.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Stimulatory and inhibitory properties of aminoglycoside antibiotics at N-methyl-D-aspartate receptors. AU - Masuko,T, AU - Kuno,T, AU - Kashiwagi,K, AU - Kusama,T, AU - Williams,K, AU - Igarashi,K, PY - 1999/8/24/pubmed PY - 1999/8/24/medline PY - 1999/8/24/entrez SP - 1026 EP - 33 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 290 IS - 3 N2 - The effects of aminoglycoside antibiotics on N-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 > paromomycin > gentamicin C > geneticin > kanamycin A > 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. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/10454474/Stimulatory_and_inhibitory_properties_of_aminoglycoside_antibiotics_at_N_methyl_D_aspartate_receptors_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=10454474 DB - PRIME DP - Unbound Medicine ER -