Effects of β-adrenergic receptor activation on alveolar macrophage cytoplasmic motility

We studied the effects of fenoterol, a β-adrenoceptor agonist, on the 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 lavage. Remanent field strength (RFS) from the AM containing Fe₃O₄ particles (5 x 10⁶ cells) was measured immediately after magnetization. RFS 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 (λ₀; min^-1) in a concentration-dependent fashion with the maximum effect at 10^-6 M. Both forskolin (10^-6 M to 10^-4 M) and dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP) (10^-3 M) mimicked fenoterol- induced inhibitory effects on λ₀. Fenoterol and forskolin concentration- dependently increased intracellular levels of cAMP, which were parallel to decreases in λ₀ 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 λ₀ (P < 0.01). These results imply that β- adrenergic receptor activation inhibits cytoplasmic motility of AM via increases in intracellular levels of cAMP, which may be coupled with activation of a cAMP-dependent protein kinase.