The basenji-greyhound dog: increased m2 muscarinic receptor
expression in trachealis muscle .
Emala, C. W., A. Aryana, M. A. Levine, R. P. Yasuda, S. A. Satkus, B.
B. Wolfe, and C. A. Hirshman.
Departments of Anesthesiology, Environmental Health Sciences, and
Medicine of the Johns Hopkins Medical Institutions, and the
Department of Pharmacology, Georgetown University School of
Medicine
APStracts 2:0012L, 1995.
Airway smooth muscle from asthmatic humans and from animal models of
asthma are hyporesponsive to [beta]-adrenergic agonist stimulation. Airway
smooth muscle from the Basenji-greyhound (BG) dog model of airway
hyperresponsiveness, shows reduced relaxation to isoproterenol when
the muscle is contracted with a muscarinic agonist and reduced
isoproterenol-stimulated adenylyl cyclase activity. Because adenylyl
cyclase is under dual regulation in airway smooth muscle, we now
compared muscarinic receptor coupled inhibition of adenylyl cyclase
in airway smooth muscle from BG and mongrel dogs. Inhibition of
forskolin-stimulated adenylyl cyclase activity by the muscarinic M2
agonist oxotremorine was greater in airway smooth muscle membranes
from BG as compared to mongrel controls. Saturation binding studies
with 3H-QNB showed that airway smooth muscle membranes from BG dogs
had significantly greater numbers of total muscarinic receptors than
membranes from mongrels (2911 +/- 630 and 921 +/- 143 fmol/mg membrane
protein, respectively, p= 0.002). Quantitative immunoprecipitation
studies using polyclonal antisera reactive to m2 and m3 muscarinic
receptors showed that the increased numbers of muscarinic receptors
in the BG airway smooth muscle were due to greater expression of m2
receptors (202 +/- 32 vs 113 +/- 36 fmol/mg cellular protein, BG vs
mongrel, respectively, p= 0.041) rather than m3 receptors (9.4 +/- 1.7
vs 8.7 +/- 2.0 fmol/mg cellular protein, BG vs mongrel, respectively).
The enhanced ability of muscarinic agonists to inhibit adenylyl
cyclase in BG airway smooth muscle may be in part due to the greater
numbers of muscarinic m2 receptors. Increased numbers of muscarinic
m2 receptors and inhibition of adenylyl cyclase may account in part
for impaired airway smooth muscle relaxation in the BG model of
airway hyperresponsiveness.
Received 24 August 1994; accepted in final form 26 January 1995.
APS Manuscript Number L251-4.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 24 February 1995.