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Am J Physiol Lung Cell Mol Physiol 265: L67-L72, 1993;
1040-0605/93 $5.00
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AJP - Lung Cellular and Molecular Physiology, Vol 265, Issue 1 67-L72, Copyright © 1993 by American Physiological Society


ARTICLES

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

T. Fukushima, K. Sekizawa, Y. Jin, M. Yamaya, H. Sasaki and T. Takishima
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.

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.


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