Zhao Z Y, Touitou Y
Department of Biochemistry, Faculté de Médecine Pitié-Salpêtrière, Paris, France.
Mol Cell Endocrinol. 1994 May;101(1-2):189-96. doi: 10.1016/0303-7207(94)90234-8.
In a previous study we have shown that the response of perifused pineal glands to calcium was different according to the circadian stage at which the glands were removed. This difference may be explained by circadian changes in calcium channel function. Therefore in the present study we documented the effects of calcium channel blockers in perifused rat pineal glands removed in the middle of the light and dark spans (7 and 19 HALO (hours after light onset), in a L/D 12:12 regimen). Moreover, we have studied the effect of calcium channel blockers on adrenergically stimulated pineal glands removed 7 HALO. Inorganic (Co2+ and Cd2+) and organic (nifedipine and diltiazem) calcium channel blockers at 10(-4) mol/l all significantly reduced melatonin production and this inhibition was more effective with the glands removed 7 HALO. In a concentration of 10(-)5 mol/l, only Cd2+ and diltiazem reduced melatonin production significantly in pineal glands removed 7 HALO. Verapamil at 10(-4) and 10(-5) mol/l showed no significant effect on melatonin production in glands removed both during the light and dark spans. Mn2+ at 10(-4) mol/l (but not at 10[-5] mol/l) appeared to stimulate melatonin production in glands removed both during the light and the dark (significant increase only with glands removed during the dark). Cobalt showed an immediate short inhibitory effect on both isoproterenol and norepinephrine-stimulated melatonin release, whereas nifedipine showed a significant inhibition only on isoproterenol-stimulated melatonin release. These results strongly suggest a circadian stage dependence of the pineal gland response to some calcium channel blockers and the involvement of calcium in the release of melatonin from pinealocytes.
在先前的一项研究中，我们已经表明，根据松果体被摘除时的昼夜节律阶段不同，灌流的松果体对钙的反应也有所不同。这种差异可能是由钙通道功能的昼夜节律变化所解释的。因此，在本研究中，我们记录了钙通道阻滞剂对在明暗周期中间时段（在12:12的光照/黑暗模式下，光照开始后7小时和19小时）摘除的灌流大鼠松果体的影响。此外，我们还研究了钙通道阻滞剂对在光照开始后7小时摘除的、经肾上腺素刺激的松果体的影响。10⁻⁴mol/L的无机钙通道阻滞剂（Co²⁺和Cd²⁺）和有机钙通道阻滞剂（硝苯地平和地尔硫䓬）均显著降低了褪黑素的分泌，并且这种抑制作用在光照开始后7小时摘除的松果体中更为有效。在10⁻⁵mol/L的浓度下，只有Cd²⁺和地尔硫䓬显著降低了光照开始后7小时摘除的松果体中褪黑素的分泌。10⁻⁴mol/L和10⁻⁵mol/L的维拉帕米对在光照和黑暗时段摘除的松果体中褪黑素的分泌均无显著影响。10⁻⁴mol/L的Mn²⁺（但10⁻⁵mol/L时无此作用）似乎在光照和黑暗时段摘除的松果体中均刺激了褪黑素的分泌（仅在黑暗时段摘除的松果体中有显著增加）。钴对异丙肾上腺素和去甲肾上腺素刺激的褪黑素释放均有即时的短期抑制作用，而硝苯地平仅对异丙肾上腺素刺激的褪黑素释放有显著抑制作用。这些结果强烈表明，松果体对某些钙通道阻滞剂的反应存在昼夜节律阶段依赖性，并且钙参与了松果体细胞释放褪黑素的过程。
