title: Binding of tritiated S21403 to an artificial phospholipid bilayer.
abstract: The binding of tritiated S21403, a novel insulin-releasing agent of the meglitinide family, to multilamellar liposomes formed of egg yolk phosphatidylcholine was compared to that of tritiated glibenclamide. The binding of [3H]S21403 reached equilibrium within 5 min of incubation at 37 degrees C, was virtually proportional to its concentration (2.8 to 56.0 nM) and failed to be inhibited by a much higher concentration (0.1 mM) of unlabelled S21403. It was much lower than that of [3H]glibenclamide tested at a comparable concentration (14.8 nM) and only slightly decreased by 0.1 mM unlabelled glibenclamide. The latter sulfonylurea inhibited more severely the binding of [3H]glibenclamide, which was unaffected, however, by 0.1 mM unlabelled S21403. These findings suggest a much higher affinity of glibenclamide than S21403 for the artificial phospholipid bilayer, this coinciding with a higher biological potency, as insulin secretagogue, of the hypoglycemic sulfonylurea as compared to meglitinide analog. It is proposed, therefore, that the insertion of these antidiabetic agents in the phospholipid domain of the B-cell membrane may condition their access to the ATP-responsive K+ channels known to represent the main target for their insulinotropic action.
authors.affiliation: Laboratory of Experimental Medicine, Brussels Free University, Belgium.
authors.forename: W J
authors.initials: WJ
authors.lastname: Malaisse
authors.forename: B
authors.initials: B
authors.lastname: Dard-Brunelle
mesh_terms: D001667:Binding, Competitive / Q000187:drug effects; D005905:Glyburide / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000378:metabolism*; D007211:Indoles / Q000378:metabolism*; D054833:Isoindoles; D008051:Lipid Bilayers / Q000378:metabolism*; D008081:Liposomes / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D013696:Temperature; D013997:Time Factors; D014316:Tritium
chemical_list: D007004:Hypoglycemic Agents; D007211:Indoles; D054833:Isoindoles; D008051:Lipid Bilayers; D008081:Liposomes; D010713:Phosphatidylcholines; D014316:Tritium; C087255:mitiglinide; D005905:Glyburide