Verapamil: a novel probe of surfactant secretion from rat type II pneumocytes.
Verapamil: a novel probe of surfactant secretion from rat type II pneumocytes.
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维拉帕米：大鼠 II 型肺细胞分泌表面活性剂的新型探针。
DOI：
10.1152/jappl.1989.66.3.1304
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Cosico,L
中科院分区：
文献类型：
--
作者：
Warburton,D;Parton,L;Buckley,S;Cosico,L
来自II型肺细胞的表面活性剂可预防新生儿和成人呼吸窘迫综合征中发现的肺泡肺不张。我们已经发现，维拉帕米，一个苯基烯烃与钙通道和α 1-受体结合特性，有一个多相浓度效应表面活性剂分泌从[3 H]胆碱标记的大鼠II型肺细胞培养。维拉帕米（10（-8）M）引起表面活性物质分泌的24%刺激，而在10（-6）M时发现8%抑制，在10（-4）M时发现70%刺激。在5 × 10（-4）M维拉帕米时发生乳酸脱氢酶释放。与浓度小于或等于10（-6）M的维拉帕米相比，维拉帕米（10（-4）M）也使腺苷3′5′-环一磷酸（cAMP）增加100%，普萘洛尔（10（-4）M）不能阻断这种作用。维拉帕米（10（-6）M）使磷酸肌醇（IP）的总形成量比对照细胞中IP的形成量增加23%。10（-8）M维拉帕米和10（-4）M维拉帕米对钙内流的抑制率分别为15%和37%。10（-5）M维拉帕米刺激钙外流44%。与50%有效浓度（EC_（50））的特布他林、佛波酯和ATP联合使用时，维拉帕米（10（-4）M）对表面活性物质分泌的各自作用近似相加。我们得出结论，维拉帕米有一个新的多相浓度效应表面活性剂的分泌，这似乎涉及几个信号转导途径，包括cAMP的形成，IP的形成，抑制钙流入，和刺激钙外流。
Surfactant from type II pneumocytes prevents the alveolar atelectasis found in both the neonatal and adult forms of respiratory distress syndrome. We have found that verapamil, a phenylalkene with calcium channel and alpha 1-receptor binding properties, has a multiphasic concentration effect on surfactant secretion from [3H]choline-labeled rat type II pneumocytes in culture. Verapamil (10(-8) M) caused a 24% stimulation of surfactant secretion, whereas an 8% inhibition was found at 10(-6) M and a 70% stimulation was found at 10(-4) M. Lactate dehydrogenase release occurred at 5 x 10(-4) M verapamil. Verapamil (10(-4) M) also produced a 100% increase in adenosine 3′5′-cyclic monophosphate (cAMP) in comparison with concentrations of less than or equal to 10(-6) M, an effect that could not be blocked by propranolol (10(-4) M). Verapamil (10(-6) M) increased the total formation of inositol phosphates (IP) by 23% in comparison with IP formation in control cells. Calcium influx was inhibited 15% by 10(-8) M verapamil and 37% by 10(-4) M verapamil. Calcium efflux was stimulated 44% by 10(-5) M verapamil. In combination with 50% effective concentrations (EC50) of terbutaline, phorbol ester, and ATP, the respective effects of verapamil (10(-4) M) on surfactant secretion were approximately additive. We conclude that verapamil has a novel multiphasic concentration effect on surfactant secretion, which appears to involve several signal transduction pathways including cAMP formation, IP formation, inhibition of calcium influx, and stimulation of calcium efflux.