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 (DOG) had decreased numbers of muscarinic receptors in airway smooth muscle homogenates as determined by radioligand binding with 1-[H-3]quinuclidinyl benzilate (vehicle control, 578 +/- 53 fmol/mg protein; MPS, 290 +/- 22 fmol/mg protein; DOG, 565 +/- 141 fmol/mg protein). Competition radioligand binding with the M(2)-selective antagonist tripitramine showed a decrease in both the M(2) and M(3) muscarinic receptors with no changes in receptor affinities (M(2): vehicle control, 478 +/- 41 fmol/mg protein; MPS, 265 +/- 20 fmol/mg protein, M(3): 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 M(2) and M(3) muscarinic receptors in airway smooth muscle, which, in part, may account for their beneficial effects in the treatment of asthma.