To better define the role of muscarinic receptors in lung responses and airway diseases, we characterized the binding of the M1-specific antagonist, [3H]pirenzepine (PZ), and the nonspecific (M1- and M2-) antagonist, [3H]quinuclidinyl benzilate (QNB), to human peripheral lung tissue. Data obtained from 15 different lung specimens showed that the radioligands bound to single high-affinity sites with dissociation constant (Kd) values ranging from 1 to 9 nM for [3H]PZ and 0.03 to 0.46 nM for [3H]QNB. Comparison of total binding capacity values by equilibrium experiments with [3H]PZ, unlabeled PZ, and [3H]QNB indicates that approximately one-half of the total muscarinic binding sites in human peripheral lung binds PZ with high affinity (putative M1-subtypes). Kd values for muscarinic agents determined by competition experiments with [3H]PZ were consistent with the expected rank order of potency for interactions with muscarinic receptors. Characterization of the role of these muscarinic receptor subtypes in human lung responses may lead to the development of more selective therapeutic agents for the treatment of chronic obstructive airway diseases.
Role of membrane cholesterol in differential sensitivity of muscarinic receptor subtypes to persistently bound xanomeline
