Glucocorticoid treatment decreases muscarinic receptor expression
in canine airway smooth muscle.
Emala, C. W., J. Clancy, and C. A. Hirshman.
Depts of Anesthesiology and Environmental Health Sciences, Johns
Hopkins Medical Institutions, Baltimore, Maryland 21205
APStracts 3:0230L, 1996.
Corticosteroids upregulate the [beta]-adrenergic pathway, but little
is known about corticosteroid regulation of muscarinic pathways.
Basenji-greyhound dogs treated for three days with methylprednisolone
(MPS) but not deoxycorticosterone (DOC) had decreased numbers of
muscarinic receptors in airway smooth muscle homogenates as
determined by radioligand binding with [3H-QNB] (vehicle control 578
+/- 53 fmol/mg protein; MPS 290 +/- 22 fmol/mg protein; DOC 565 +/-
141 fmol/mg protein). Competition radioligand binding with the M2
-selective antagonist tripitramine, showed a decrease in both the M2
and M3 muscarinic receptors with no changes in receptor affinities
(M2: vehicle control 478 +/- 41 fmol/mg protein; MPS 265 +/- 20
fmol/mg protein, M3: vehicle control 89 +/- 13 fmol/mg protein; MPS
25 +/- 16 fmol/mg protein). In vitro treatment of airway smooth
muscle from control BG dogs with MPS had no effect on muscarinic
receptor number despite increased expression of [beta]-adrenergic
receptors. Thus, glucocorticoids indirectly decrease the expression
of M2 and M3 muscarinic receptors in airway smooth muscle which in
part may account for their beneficial effects in the treatment of
asthma.
Received 25 July 1996; accepted in final form 14 November 1996.
APS Manuscript Number L237-6.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996