Fukushima T, Sekizawa K, Jin Y, Yamaya M, Sasaki H, Takishima T
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Am J Physiol. 1993 Jul;265(1 Pt 1):L67-72. doi: 10.1152/ajplung.1993.265.1.L67.
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.
我们在体外研究了β-肾上腺素能受体激动剂非诺特罗对犬肺肺泡巨噬细胞（AM）胞质运动的影响。向下叶支气管内滴注Fe3O4颗粒（3mg/kg）4天后，通过支气管肺泡灌洗收集AM。对含有Fe3O4颗粒（5×10⁶个细胞）的AM进行磁化后立即测量剩余场强（RFS）。由于颗粒旋转（弛豫），RFS随时间下降，这与AM的胞质运动有关。非诺特罗（10⁻⁹M至10⁻⁵M）以浓度依赖的方式降低弛豫率（λ₀；min⁻¹），在10⁻⁶M时效果最佳。福斯可林（10⁻⁶M至10⁻⁴M）和二丁酰腺苷3'，5'-环磷酸腺苷（cAMP）（10⁻³M）均模拟了非诺特罗对λ₀的抑制作用。非诺特罗和福斯可林浓度依赖性地增加细胞内cAMP水平，这与这些药物诱导的λ₀降低平行。蛋白激酶A的特异性抑制剂KT 5720（10⁻⁵M）显著抑制非诺特罗（10⁻⁶M）对λ₀的抑制作用（P<0.01）。这些结果表明，β-肾上腺素能受体激活通过增加细胞内cAMP水平来抑制AM的胞质运动，这可能与cAMP依赖性蛋白激酶的激活有关。
