TGF-beta 1 modulates beta-adrenergic receptor number and function in cultured human tracheal smooth muscle cells.
TGF-beta 1 modulates beta-adrenergic receptor number and function in cultured human tracheal smooth muscle cells.
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TGF-β1 调节培养的人气管平滑肌细胞中 β-肾上腺素能受体的数量和功能。
DOI：
10.1152/ajplung.1994.266.2.l187
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
M. Toews
中科院分区：
文献类型：
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作者：
M. Nogami;D. Romberger;S. Rennard;M. Toews
用转化生长因子-β 1（TGF-β 1）预处理培养的人气管平滑肌细胞，可减少β-肾上腺素能激动剂异丙肾上腺素刺激的完整细胞中腺苷3 '，5'-环磷酸（cAMP）的积累。TGF-β 1对异丙肾上腺素刺激的cAMP蓄积的最大抑制为31 +/-3%，TGF-β 1的平均有效浓度（EC 50）约为1.5 pM。TGF-β 1降低对异丙肾上腺素的最大反应，但不改变异丙肾上腺素的EC 50值。TGF-β 1不改变毛喉素刺激的cAMP积累。TGF-β 1预处理降低了破碎细胞制备物中测得的异丙肾上腺素刺激的腺苷酸环化酶活性，但没有改变氟化物刺激的腺苷酸环化酶活性。总之，这些结果表明，TGF-β 1的作用不是通过直接抑制腺苷酸环化酶或通过降低刺激性GTP结合蛋白的活性。β-肾上腺素能受体放射性配体[125 I]碘吲哚饱和结合实验表明，TGF-β 1预处理减少β-肾上腺素能受体的数量。蛋白质合成抑制剂放线菌酮消除了TGF-β 1对cAMP积累和β-肾上腺素能受体数量的影响，表明蛋白质合成参与其中。这些结果表明，肺中的TGF-β 1可能在改变气道平滑肌细胞对内源性儿茶酚胺和治疗中使用的β-肾上腺素能激动剂的反应性方面发挥作用。
Pretreatment of cultured human tracheal smooth muscle cells with transforming growth factor-beta 1 (TGF-beta 1) decreased adenosine 3',5'-cyclic monophosphate (cAMP) accumulation by intact cells stimulated with the beta-adrenergic agonist isoproterenol. The maximal inhibition of isoproterenol-stimulated cAMP accumulation by TGF-beta 1 was 31 +/- 3%, and the mean effective concentration (EC50) of TGF-beta 1 was approximately 1.5 pM. TGF-beta 1 decreased the maximal response to isoproterenol but did not change the EC50 value of isoproterenol. TGF-beta 1 did not change cAMP accumulation stimulated by forskolin. TGF-beta 1 pretreatment decreased isoproterenol-stimulated adenylyl cyclase activity measured in broken cell preparations, but did not change the fluoride-stimulated adenylyl cyclase activity. Together these results suggest that the TGF-beta 1 effect is not by direct inhibition of adenylyl cyclase or by decreased activity of the stimulatory GTP-binding protein. Saturation binding experiments with the beta-adrenergic receptor radioligand [125I]iodopindolol showed that TGF-beta 1 pretreatment decreased the beta-adrenergic receptor number. The protein synthesis inhibitor cycloheximide abolished the effect of TGF-beta 1 on both cAMP accumulation and on beta-adrenergic receptor number, indicating that protein synthesis is involved. These results suggest that TGF-beta 1 in the lung could play a role in changing the responsiveness of airway smooth muscle cells to endogenous catecholamines and to beta-adrenergic agonists used in therapy.