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.