[Stimulation of ciliary motility by beta 3-adrenoceptor agonist rabbit tracheal epithelium].
To determine whether atypical beta-adrenoceptor (beta 3-adrenoceptor) agonist, BRL 37344, stimulates airway ciliary motility and, if so, what its mechanism of action is, we studied rabbit tracheal epithelium in vitro. Epithelial cells cultured for 7 days were mounted in the Rose chamber and ciliary beat frequency (CBF) was measured by a photoelectric method. Addition of BRL 37344 rapidly increased CBF from 15.5 +/- 0.6 to 20.3 +/- 1.4 Hz (mean +/- SE, p < 0.01), which remained elevated for at least 20 min. This effect was concentration-dependent, the maximal increase from the baseline value and the EC50 being 27.2 +/- 0.4% (mean +/- SE, p < 0.01) and 1.75 x 10(-7) M, respectively. Other beta-adrenoceptor agonists likewise increased CBF, where the rank order of potency was salbutamol (1) > BRL 37344 (0.57) >> norepinephrine (1.3 x 10(-3)). Preincubation of cells with propranolol inhibited the increase in CBF produced by salbutamol, and BRL 37344 significantly raised intracellular cyclic AMP contents. These results suggest that beta 3-adrenoceptor probably exists in rabbit tracheal epithelium and that stimulation of this type of receptor increases ciliary motility through a cyclic AMP-dependent mechanism, an effect that might be of value in enhancing mucociliary transport function in the airway.
Takeyama
K
K
First Department of Medicine, Tokyo Women's Medical College.
Tamaoki
J
J
Chiyotani
A
A
Sakai
N
N
Kanemura
T
T
Konno
K
K
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000187:drug effects; D004983:Ethanolamines / Q000494:pharmacology*; D008297:Male; D009079:Mucociliary Clearance / Q000187:drug effects*; D011817:Rabbits; D014132:Trachea / Q000187:drug effects*
D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; C057368:BRL 37344; D000242:Cyclic AMP