Rat lung cholinergic receptor: characterization and regulation by corticosteroids.

Muscarinic cholinergic receptors have been implicated in the regulation of bronchomotor tone, bronchial mucus secretion, and lung mast-cell mediator release. Rat lung membranes prepared by homogenization, sonication, and sedimentation of 37,000 g in sucrose have been demonstrated to possess muscarinic cholinergic receptors as assessed by radioligand binding employing l-quinuclidinyl[phenyl-4-3H]benzilate ([3H]QNB). QNB binding was saturable, stereoselective, and reversible in the presence of 1 microM atropine. The rat lung muscarinic receptor demonstrated a Kd of 0.268 +/- 0.126 (+/- SD) nM and a density of 35.4 +/- 4.6 fmol/mg protein by Scatchard analysis. The Hill coefficient was 1.015 +/- 0.085, indicating noncooperative binding. Muscarinic cholinergic receptors in the rat lung were equal in number to alpha 1-adrenergic receptors, but beta-adrenergic receptors are 14 times more prevalent as defined by [3H]prazosin and l-[propyl-2, 3-3H]dihydroalprenolol ([3H]DNA) binding. Dexamethasone (140 micrograms) administration in vivo caused an increase in all three receptor types by 24-48 h, suggesting steroids regulate not only the number of beta-receptors but also that of alpha- and cholinergic receptors. These data suggest new avenues by which steroids may regulate lung function.