Inhibition and facilitation by pimobendan, a calcium sensitizer, of catecholamine secretion from bovine adrenal chromaffin cells.
Inhibition and facilitation by pimobendan, a calcium sensitizer, of catecholamine secretion from bovine adrenal chromaffin cells.
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DOI：
10.1254/jphs.91.211
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发表时间：
2003
影响因子：
3.5
通讯作者：
H. Kuwashima;C. Matsumura;Tomohiko Kimura
中科院分区：
文献类型：
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作者：
H. Kuwashima;C. Matsumura;Tomohiko Kimura
在牛肾上腺嗜铬细胞中研究了匹莫苯丹（一种 Ca(2+) 敏化剂，对环 GMP 抑制的磷酸二酯酶 (PDE-III) 具有抑制作用）对儿茶酚胺 (CA) 分泌的影响。在完整细胞中，匹莫苯丹 (10 - 100 µM) 抑制乙酰胆碱（10 和 30 µM）和 1,1-二甲基-4-苯基哌嗪鎓 (DMPP)（3 和 10 µM）刺激的 CA 分泌，但促进高 K(+) (30 mM)、组胺 (3 µM) 和血管紧张素-II (3 µM) 刺激的 CA 分泌。组胺和血管紧张素II对无Ca(2+)培养基中的CA分泌没有影响。匹莫苯对刺激诱发的 CA 分泌的抑制或促进作用不受环 AMP 依赖性蛋白激酶抑制剂 H-89 (1 µM) 和 H-8 (30 µM) 的影响。 PDE-III 抑制剂米力农（10 和 30 µM）和氨力农（100 和 300 µM）不影响刺激诱发的 CA 分泌。在β-七叶皂苷透化细胞中，在存在和不存在 MgATP (2 mM) 的情况下，匹莫苯丹 (10 - 100 microM) 不会影响 Ca(2+) (0.1 - 10 microM) 刺激的 CA 分泌。这些结果表明，匹莫苯丹对 CA 分泌具有抑制和促进双重作用。抑制可能是由于对烟碱受体的抑制作用，而促进作用可能是由于对刺激诱导的Ca(2+)流入的促进作用。 Ca(2+) 致敏作用和 PDE-III 抑制作用似乎均与这些作用无关。
The effects of pimobendan, a Ca(2+) sensitizer with inhibitory action against cyclic-GMP-inhibited phosphodiesterase (PDE-III), on catecholamine (CA) secretion were studied in bovine adrenal chromaffin cells. In intact cells, pimobendan (10 - 100 microM) inhibited CA secretion stimulated by acetylcholine (10 and 30 microM) and 1,1-dimethyl-4-phenyl-piperazinium (DMPP) (3 and 10 microM), but facilitated CA secretion stimulated by high K(+) (30 mM), histamine (3 microM), and angiotensin-II (3 microM). Histamine and angiotensin-II had no effect on CA secretion in Ca(2+)-free medium. The inhibition or facilitation by pimobendan of the stimulation-evoked CA secretion was not affected by H-89 (1 microM) and H-8 (30 microM), inhibitors of cyclic-AMP-dependent protein kinase. Milrinone (10 and 30 microM) and amrinone (100 and 300 microM), inhibitors of PDE-III, did not affect the stimulation-evoked CA secretion. In beta-escin-permeabilized cells, pimobendan (10 - 100 microM) did not affect CA secretion stimulated by Ca(2+) (0.1 - 10 microM) in the presence and absence of MgATP (2 mM). These results indicate that pimobendan has dual effects, inhibition and facilitation, on CA secretion. The inhibition may be due to an inhibitory action on nicotinic receptors and the facilitation may be due to a facilitatory action on stimulation-induced Ca(2+) influx. Neither Ca(2+) sensitizing nor PDE-III inhibiting actions seem to be related to these effects.