The M2 selective antagonist AF-DX 116 shows high affinity for muscarine receptors in bovine tracheal membranes.
We have characterized the muscarine receptors in bovine tracheal and left ventricular membranes using 3H-dexetimide/pirenzepine and 3H-dexetimide/AF-DX 116 competition studies. Pirenzepine exhibited low (M2) affinity binding to both preparations; Kd was 590 nM in left ventricle and 463 nM in trachea. AF-DX 116 exhibited high (M2) affinity binding to left ventricle (Kd = 95.6 nM); in tracheal membranes it bound with high (M2) affinity (Kd = 40.7 nM) to 74% of the receptors and with low (M3) affinity (Kd = 2.26 microM) to 26% of the receptors. It is concluded that bovine tracheal muscle membranes contain a heterogeneous population of muscarine binding sites, the majority having M2 (heart) subtype characteristics and being located on the smooth muscle membranes; a minority having M3 (exocrine gland) subtype characteristics and presumed to be located in submucosal glands. This is the first report of high affinity binding of AF-DX 116 to non-cardiac peripheral muscarine receptors.
D000818:Animals; D001667:Binding, Competitive; D002417:Cattle; D003909:Dexetimide / Q000378:metabolism; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000378:metabolism; D009130:Muscle, Smooth / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism*; D014132:Trachea / Q000378:metabolism
D008565:Membrane Proteins; D011976:Receptors, Muscarinic; D010890:Pirenzepine; D003909:Dexetimide; C048593:otenzepad