AJP - Cell Physiology, Vol 258, Issue 6 C982-C987, Copyright © 1990 by American Physiological Society
Characterization of a muscarinic receptor controlling Cl- secretion in hen trachea
B. Winding and N. Bindslev
Department of General Physiology and Biophysics, Panum Institute, University of Copenhagen, Denmark.
We have attempted to characterize a muscarinic receptor subtype involved in
Cl- secretion in isolated epithelium of hen trachea, taking advantage of
drugs developed in the last 15 yr. Hen trachea can be stimulated to secrete
Cl- equal to approximately 80-90 microA/cm2 by application of acetylcholine
(ACh) to the serosal side. The process has an apparent dissociation
constant (Kd) for ACh of 740 nM. The Cl- secretion is completely inhibited
by 20 microM bumetanide at the serosal side. Of five selective antagonists
for muscarinic receptors, pirenzepine, hexahydrosiladifenidol, dicyclomine,
11-([2-[(diethylamino)-methyl]-1-piperidinyl]acetyl)-5,11-
dihydro-6H-pyrido(2,3-b)(1,4)benzodiazepine-6-one, and 4 diphenyl
acetoxy-N-methylpiperidine methobromide, only the latter had a high
affinity for the functional receptor with an apparent Kd of 3 nM. The
receptor may be classified as an M4-muscarinic receptor subtype and
probably belongs to a group of muscarinic receptors on exocrine glands and
mucosal cells involved in ion transport. All the functional responses
caused by muscarinic agonists and antagonists tested exhibited exponents
(apparent Hill coefficients) in the range from 1.3 to 2.4, indicating a
gain in the stimulus secretion coupling mechanism, an aspect of muscarinic
receptor function that is not revealed in radioligand binding studies.
