Journal of Applied Physiology, Vol 65, Issue 2 594-600, Copyright © 1988 by American Physiological Society
Characterization of muscarinic receptor subtypes on human peripheral lung
T. B. Casale and P. Ecklund
Department of Internal Medicine, Veterans Administration Medical Center, Iowa City, Iowa.
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.
