Dihydropyridine Ca2+ antagonists: potent inhibitors of secretion from normal and transformed pituitary cells.
Dihydropyridine Ca2+ antagonists: potent inhibitors of secretion from normal and transformed pituitary cells.
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二氢吡啶 Ca2 拮抗剂：正常和转化垂体细胞分泌的有效抑制剂。
DOI：
10.1152/ajpcell.1985.248.5.c510
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
Hinkle,PM
中科院分区：
文献类型：
--
作者：
Enyeart,JJ;Aizawa,T;Hinkle,PM
三个二氢吡啶（DHP）的钙离子拮抗剂与其他几个有机钙离子拮抗剂的能力，抑制去极化依赖性激素分泌的GH4 C1垂体细胞系和正常大鼠垂体细胞进行了比较。这三种DHP，尼莫地平，尼索地平，硝苯地平，强效和特异性抑制KCl刺激的催乳素分泌从GH4 C1细胞（估计的IC 50值：1.8，1.8，和6.0 nM，分别）。基础和促甲状腺激素释放激素刺激的GH4 C1细胞分泌的DHP抑制的敏感性要低得多。由DHP的抑制是可逆的，其效力是独立的去极化浓度的KCl之间的18.8和53.8 mM. Other有机拮抗剂，包括维拉帕米，桂利嗪，和地尔硫卓，阻止GH4 C1细胞的分泌，但在更高的浓度。这三种药物的估计IC 50值分别为1，000、1，100和3，500 nM。去极化刺激的催乳素分泌从正常垂体抑制DHP和维拉帕米在相同的浓度发现有效的GH4 C1细胞。KCl刺激的GH4 C1细胞的~（45）Ca ~（2+）摄取也被DHP在抑制分泌的浓度下阻断。由于去极化刺激的分泌和~（45）Ca ~（2+）摄取可能是由Ca ~（2+）通过电压敏感性通道进入触发的，上述结果表明，DHP拮抗剂在正常和转化垂体细胞中都有效地阻断这些通道。这些Ca 2+通道在这方面似乎是相同的。这些发现进一步表明内分泌细胞的Ca 2+通道与平滑肌和其他可兴奋细胞的Ca 2+通道之间的相似性。
Three dihydropyridine (DHP) Ca2+ antagonists were compared with several other organic Ca2+ antagonists with respect to their ability to inhibit depolarization-dependent hormone secretion from the GH4C1 pituitary cell line and from normal rat pituitary cells. The three DHP, nimodipine, nisoldipine, and nifedipine, potently and specifically inhibited KCl-stimulated prolactin secretion from GH4C1 cells (estimated IC50 values: 1.8, 1.8, and 6.0 nM, respectively). Both basal and thyrotropin-releasing hormone-stimulated secretion from GH4C1 cells were much less sensitive to inhibition by the DHP. The inhibition by the DHP was reversible, and their potency was independent of depolarizing concentrations of KCl between 18.8 and 53.8 mM. Other organic antagonists, including verapamil, cinnarizine, and diltiazem, blocked secretion from GH4C1 cells but at much higher concentrations. The estimated IC50 values for these three were 1,000, 1,100, and 3,500 nM, respectively. Depolarization-stimulated prolactin secretion from normal pituitaries was inhibited by the DHP and verapamil at the same concentrations found effective in GH4C1 cells. KCl-stimulated 45Ca2+ uptake by GH4C1 cells was also blocked by DHP at concentrations that inhibited secretion. Since depolarization-stimulated secretion and 45Ca2+ uptake are probably triggered by Ca2+ entering through voltage-sensitive channels, the above results suggest that DHP antagonists potently block these channels in both normal and transformed pituitary cells. These Ca2+ channels appear to be identical in this respect. These findings further suggest a similarity between the Ca2+ channels of endocrine cells and those of smooth muscle and other excitable cells.