Title

Comparative studies of anthraquinone- and anthracene-tetraamines as blockers of N-methyl-D-aspartate receptors

Authors

Authors

L. H. Jin; H. Sugiyama; M. Takigawa; D. Katagiri; H. Tomitori; K. Nishimura; N. Kaur; O. Phanstiel; M. Kitajima; H. Takayama; T. Okawara; K. Williams; K. Kashiwagi;K. Igarashi

Comments

Authors: contact us about adding a copy of your work at STARS@ucf.edu

Abbreviated Journal Title

J. Pharmacol. Exp. Ther.

Keywords

NMDA RECEPTOR; CHANNEL BLOCKERS; SELECTIVITY FILTER; ION CHANNELS; POLYAMINES; ANTAGONISTS; TRANSMEMBRANE; PERMEATION; MECHANISMS; EXPRESSION; Pharmacology & Pharmacy

Abstract

Anthraquinone spermine [N-1-(anthraquinone-2-carbonyl)spermine; AQ343], anthraquinone homospermine [N-1-anthraquinone-2-carbonyl; AQ444], anthracene spermine [N-1-(9-anthracenylmethyl)spermine; Ant343], and anthracene homospermine [N-1-(9-anthracenylmethyl) homospermine; Ant444] were found to be potent antagonists of recombinant N-methyl-D-aspartate (NMDA) receptors (NRs). The effects of both anthraquinone (AQ)- and anthracene (Ant)-tetraamines were reversible and voltage-dependent. Results of experiments using mutant NR1 and NR2B subunits of NMDA receptor identified residues that influence block by AQ- and Ant-tetraamines. The results indicate that the polyamine tail is crucial for block by AQ- and Ant-tetraamines. Residues in the outer vestibule of the NR1 subunit were more strongly involved in block by AQ- and Ant-tetraamines than residues in the corresponding region of NR2B. Several amino acid residues in the inner vestibule, below the level of the selectivity filter of NR1 and NR2B, affected block by AQ444, Ant343, and Ant444, but they did not affect block by AQ343. AQ-tetraamines could permeate the channel at very negative membrane potentials when the narrowest constriction of the channel was expanded by replacing the Asn residue at Asn616 of NR1 and NR2B with Gly, whereas Ant-tetraamines did not easily pass through the channel, apparently because of differences in the relative position of the head groups on AQ- and Ant- polyamines.

Journal Title

Journal of Pharmacology and Experimental Therapeutics

Volume

320

Issue/Number

1

Publication Date

1-1-2007

Document Type

Article

DOI Link

http://dx.doi.org/10.1124/jpet.106.110528

Language

English

First Page

47

Last Page

55

WOS Identifier

WOS:000242995600006

ISSN

0022-3565

Recommended Citation

"Comparative studies of anthraquinone- and anthracene-tetraamines as blockers of N-methyl-D-aspartate receptors" (2007). Faculty Bibliography 2000s. 7271.
https://stars.library.ucf.edu/facultybib2000/7271