Mak_1989_Eur.J.Pharmacol_164_223

Muscarinic receptor subtypes in human and guinea pig lung membranes were characterised using selective muscarinic antagonists. Competition experiments were carried out against [3H](-)-quinuclidinyl benzilate binding at 25 degrees C in Tris-HCl buffer; non-specific binding was determined in the presence of 1 microM atropine. Of all the antagonists examined, only the M1-selective antagonist pirenzepine exhibited a heterogeneous binding profile (nH less than 1.0), best described by two-binding sites of high and low affinity. Binding of [3H]pirenzepine confirmed the presence of a high proportion of high affinity (M1) receptors (60% of total) in human peripheral lung. The high potency of M3-selective antagonists 4-diphenylacetoxy-N-methyl-piperidine methiodide (4-DAMP) and hexahydrosiladifenidol suggested the presence of M3 receptors, but the low potency of AF-DX 116 and methoctramine indicated that there was no significant population of M2 receptors present. The existence of muscarinic receptor subtypes in lung may have important clinical implication but their cellular localisation remains to be determined.