The effects of alanine-substituted conantokin-G and ifenprodil on the human spermine-activated N-methyl-D-aspartate receptor.
We evaluated the effects of Ala-7-conantokin-G (Con-G(A7)) and ifenprodil on the modulation by spermine of [(3)H]MK801 binding to human cortical membranes. Human cortical tissue was obtained at autopsy and stored at -80 degrees C until assay. Both Con-G(A7) and ifenprodil inhibited [(3)H]MK801 binding, but spermine affected these inhibitions differently. Con-G(A7) IC(50) changed little with spermine concentration, indicative of a non-competitive interaction, whereas the rightward shift in ifenprodil IC(50) with increasing spermine concentration suggested partial competition. When the two agents were tested against the biphasic activation of [(3)H]MK801 binding by spermine, they again differed in their effects. In the activation phase Con-G(A7) was a non-competitive inhibitor of spermine activation, and may even enhance the spermine EC(50), while the ifenprodil data indicated a partially competitive interaction. Both agents were non-competitive in the inhibitory phase. Overall, the data suggest that Con-G(A7) and ifenprodil interact differently with the polyamine modulation of the glutamate-N-methyl-D-aspartate receptor.
Tsai
V W-W
VW
School of Molecular and Microbial Sciences, University of Queensland, Brisbane 4072, Australia.
Dodd
P R
PR
Lewis
R J
RJ
D000409:Alanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects* / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D020916:Conotoxins / Q000737:chemistry / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000378:metabolism / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D011869:Radioligand Assay; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000378:metabolism; D013096:Spermine / Q000494:pharmacology*
D020916:Conotoxins; D018691:Excitatory Amino Acid Antagonists; D009498:Neurotoxins; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D013096:Spermine; D016291:Dizocilpine Maleate; C055407:conotoxin GV; D000409:Alanine; C010739:ifenprodil