EFFECTS OF BETA-ADRENERGIC-RECEPTOR ACTIVATION ON ALVEOLAR MACROPHAGECYTOPLASMIC MOTILITY

We studied the effects of fenoterol, a beta-adrenoceptor agonist, on t he cytoplasmic motility of alveolar macrophages (AM) from dog lungs in vitro. Four days after the instillation of Fe3O4 particles (3 mg/kg) into the lower lobe bronchus, AM were harvested by bronchoalveolar lav age. Remanent field strength (RFS) from the AM containing Fe3O4 partic les (5 X 10(6) cells) was measured immediately after magnetization. RF S decreased with time due to particle rotation (relaxation), which is related to cytoplasmic motility of AM. Fenoterol (10(-9) M to 10(-5) M ) decreased the relaxation rate (lambda0; min-1) in a concentration-de pendent fashion with the maximum effect at 10(-6) M. Both forskolin (1 0(-6) M to 10(-4) M) and dibutyryl adenosine 3',5'-cyclic monophosphat e (cAMP) (10(-3) M) mimicked fenoterol-induced inhibitory effects on l ambda0. Fenoterol and forskolin concentration-dependently increased in tracellular levels of cAMP, which were parallel to decreases in lambda 0 induced by these drugs. KT 5720 (10(-5) M), a specific inhibitor of protein kinase A, significantly inhibited fenoterol (10(-6) M)-induced inhibitory effects on lambda0 (P < 0.01). These results imply that be ta-adrenergic receptor activation inhibits cytoplasmic motility of AM via increases in intracellular levels of cAMP, which may be coupled wi th activation of a cAMP-dependent protein kinase.