Methyllycaconitine: a selective probe for neuronal alpha-bungarotoxin binding sites.
The ability of methyllycaconitine (MLA) to inhibit the binding of [125I]alpha-bungarotoxin to rat brain membranes, frog and human muscle extracts and the human muscle cell line TE671 has been measured. MLA showed a markedly higher affinity for the rat brain site (Ki 1.4 x 10(-9) M) than for the muscle receptors (Ki 10(-5)-10(-6) M). Structure modelling techniques were used to fit the structure of MLA to a nicotinic pharmacophore model. MLA is the first low molecular weight ligand to be shown to discriminate between muscle nicotinic receptors and their alpha-bungarotoxin-binding counterpart in the brain, and as such may be a useful structural probe for pursuing the structural and functional properties of the neuronal protein.
Ward
J M
JM
Department of Biochemistry, University of Bath, UK.
Cockcroft
V B
VB
Lunt
G G
GG
Smillie
F S
FS
Wonnacott
S
S
D000157:Aconitine / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D001001:Anura; D001667:Binding, Competitive; D002038:Bungarotoxins / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008958:Models, Molecular; D009132:Muscles / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D011950:Receptors, Cholinergic / Q000378:metabolism*; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor
D002038:Bungarotoxins; C579167:Chrna7 protein, human; C579165:Chrna7 protein, rat; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C054634:methyllycaconitine; D000157:Aconitine