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4‐Oxystilbene compounds are selective ligands for neuronal nicotinic α Bungarotoxin receptors
Author(s) -
Gotti C.,
Balestra B.,
Moretti M.,
Rovati G. E.,
Maggi L.,
Rossoni G.,
Berti F.,
Villa L.,
Pallavicini M.,
Clementi F.
Publication year - 1998
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0701957
Subject(s) - acetylcholine receptor , receptor , homomeric , nicotinic agonist , bungarotoxin , epibatidine , acetylcholine , stimulation , chemistry , alpha 4 beta 2 nicotinic receptor , biochemistry , microbiology and biotechnology , medicine , endocrinology , biology , nicotinic acetylcholine receptor , protein subunit , gene
1 Starting from the structure of an old 4‐oxystilbene derivate with ganglioplegic activity (MG624), we synthesized two further derivates (F2 and F3) and two stereoisomers of F3 (F3A and F3B), and studied their selective effect on neuronal nicotinic acetylcholine receptor (AChR) subtypes. 2 MG 624, F3, F3A and F3B inhibited of 125 I‐αBungarotoxin (αBgtx) binding to neuronal chick optic lobe (COL) membranes, with nM affinity, but inhibited 125 I‐αBgtx binding to TE671 cell‐expressed muscle‐type AChR only at much higher concentrations. 3 We immobilized the α7, β2 and β4 containing chick neuronal nicotinic AChR subtypes using anti‐subunit specific antibodies. MG 624, F3, F3A and F3B inhibited 125 I‐αBgtx binding to the α7‐containing receptors with n m affinity, but inhibited 3 H‐Epi binding to β2‐containing receptors only at very high concentrations (more than 35 μ m ); their affinity for the β4‐containing receptors was ten times more than for the β2‐containing subtype. 4 Both MG624 and F3 compounds inhibited the ACh evoked currents in homomeric oocyte‐expressed chick α7 receptors with an IC 50 of respectively 94 and 119 n m . 5 High doses of both MG 624 and F3 depressed the contractile response to vagus nerve stimulation in guinea pig nerve‐stomach preparations although at different IC 50 s (49.4 vs 166.2 μ m ) The effect of MG624 on rat nerve‐hemidiaphragm preparations was 33 times less potent than that of F3 (IC 50 486 vs 14.5 μ m ). 6 In conclusion, MG624 and F3 have a high degree of antagonist selectivity for neuronal nicotinic αBgtx receptors containing the α7 subunit.British Journal of Pharmacology (1998) 124 , 1197–1206; doi: 10.1038/sj.bjp.0701957