Effects of beta-adrenergic receptor activation on alveolar macrophage cytoplasmic motility.
We studied the effects of fenoterol, a beta-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 10(6) 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 (lambda 0; 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 lambda 0. Fenoterol and forskolin concentration-dependently increased intracellular 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 lambda 0 (P < 0.01). These results imply that beta-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.
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
T
T
Fukushima
K
K
Sekizawa
Y
Y
Jin
M
M
Yamaya
H
H
Sasaki
T
T
Takishima
D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002772:Cholera Toxin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism / Q000502:physiology*; D004285:Dogs; D005280:Fenoterol / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000378:metabolism / Q000502:physiology*; D047428:Protein Kinase Inhibitors; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
D047428:Protein Kinase Inhibitors; D011943:Receptors, Adrenergic, beta; D005280:Fenoterol; D002772:Cholera Toxin; D000242:Cyclic AMP