Glucocorticoid treatment decreases muscarinic receptor expression in canine airway smooth muscle.
Corticosteroids upregulate the beta-adrenergic pathway, but little is known about corticosteroid regulation of muscarinic pathways. Basenji-greyhound (BG) dogs treated for 3 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 1-[3H]quinuclidinyl benzilate (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.
Emala
C W
CW
Department of Anesthesiology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA.
Clancy
J
J
Hirshman
C A
CA
D000818:Animals; D001569:Benzodiazepines / Q000378:metabolism; D001667:Binding, Competitive; D003900:Desoxycorticosterone / Q000494:pharmacology; D003959:Diamines / Q000378:metabolism; D004285:Dogs; D005938:Glucocorticoids / Q000494:pharmacology*; D066298:In Vitro Techniques; D008775:Methylprednisolone / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009130:Muscle, Smooth / Q000378:metabolism*; D010276:Parasympatholytics / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism*; D014132:Trachea / Q000378:metabolism*
D003959:Diamines; D005938:Glucocorticoids; D018727:Muscarinic Antagonists; D010276:Parasympatholytics; D011976:Receptors, Muscarinic; D001569:Benzodiazepines; C084480:tripitramine; D003900:Desoxycorticosterone; C054938:methoctramine; D008775:Methylprednisolone