The M2 selective antagonist AF-DX 116 shows high affinity for mnscarine receptors in bovine tracheal membranes

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Abstract
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. Pirenzepinc exhibited low (M2) affinity binding to both preparations; K d was 590 nM in left ventricle and 463 nM in trachea. AF-DX 116 exhibited high (M2) affinity binding to left ventricle (K d = 95.6 nM); in tracheal membranes it bound with high (M2) affinity (K d = 40.7 nM) to 74% of the receptors and with low (M3) affinity (K d = 2.26 μM) 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.