Endogenous indoles as novel polyamine site ligands at the N-methyl-D-aspartate receptor complex.
High-throughput ligand displacement screens of a series of endogenous indoles revealed that tryptamine, serotonin and 5-methoxytryptamine readily displace [3H]spermidine and [3H]MK-801 from their respective binding sites in rat brain homogenate. These data, coupled with their potent inhibition of spermidine-potentiated [3H]MK-801 binding, suggest that certain endogenous indoles may act as ligands to one or more polyamine binding sites in the brain, including those on the N-methyl-D-aspartate receptor complex.
Worthen
D R
DR
Division of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0082, USA.
Gibson
D A
DA
Rogers
D T
DT
Bence
A K
AK
Fu
M
M
Littleton
J M
JM
Crooks
P A
PA
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology*; D015317:Biogenic Polyamines / Q000737:chemistry / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007211:Indoles / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D008024:Ligands; D018696:Neuroprotective Agents / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism*; D013095:Spermidine / Q000494:pharmacology; D013347:Subcellular Fractions / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D014316:Tritium
D015317:Biogenic Polyamines; D018691:Excitatory Amino Acid Antagonists; D007211:Indoles; D008024:Ligands; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D014316:Tritium; D016291:Dizocilpine Maleate; D013095:Spermidine