Conantokin-T selectively antagonizes N-methyl-D-aspartate-evoked responses in rat hippocampal slice.
This study investigated the mode of action of conantokin-T, a 21 amino acid peptide toxin isolated from the venom of the fish-hunting cone snail Conus tulipa, on excitatory synaptic transmission in rat hippocampal slices using intracellular recording techniques. Superfusion of conantokin-T (1-500 nM) specifically and irreversibly decreased the pharmacologically isolated N-methyl-D-aspartate receptor (NMDA)-mediated excitatory postsynaptic potential (EPSPNMDA) in a concentration-dependent manner but had no effect on normal excitatory synaptic transmission (EPSP). The sensitivity of postsynaptic neurons to NMDA but not to alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid was also antagonized by conantokin-T pretreatment. In addition, the conantokin-T-induced depression of EPSPNMDA could be antagonized by prior treatment of hippocampal slices with either DL-2-amino-5-phosphonovaleate (10 microM) or ifenprodil (20 microM). However, 7-chlorokynurenic acid (1 microM) had no effect on the action of conantokin-T. These findings indicated that conantokin-T modulates the NMDA receptor by an interaction with its glutamate binding site and polyamine recognition site.
Huang
C C
CC
Department of Pharmacology, College of Medicine, National Cheng-Kung University, Tainan, Taiwan, R.O.C.
Lyu
P C
PC
Lin
C H
CH
Hsu
K S
KS
D000818:Animals; D020916:Conotoxins; D004347:Drug Interactions; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000138:chemical synthesis / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D008978:Mollusk Venoms / Q000138:chemical synthesis / Q000494:pharmacology*; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000187:drug effects; D017470:Receptors, Glutamate / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism
D020916:Conotoxins; D018691:Excitatory Amino Acid Antagonists; D036341:Intercellular Signaling Peptides and Proteins; D008978:Mollusk Venoms; D010455:Peptides; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C063571:conantokin-T