Melatonin stimulates inositol-1,4,5-trisphosphate and Ca2+ release from INS1 insulinoma cells

被引:49
作者
Bach, AG
Wolgast, S
Mühlbauer, E
Peschke, E
机构
[1] Univ Halle Wittenberg, Inst Anat & Cell Biol, D-06097 Halle An Der Saale, Germany
[2] Saxon Acad Sci, Leipzig, Germany
关键词
beta-cell; Ca2+; INS1; insulin; IP3; receptor; melatonin;
D O I
10.1111/j.1600-079X.2005.00253.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The effects of melatonin in mammalian cells are exerted via specific receptors or are related to its free radical scavenging activity. It has previously been reported that melatonin inhibits insulin secretion in the pancreatic islets of the rat and in rat insulinoma INS1 cells via G(i)-protein-coupled MT1 receptors and the cyclic adenosine 3',5'-monophosphate pathway. However, the inositol-1,4,5-trisphosphate (IP3) pathway is involved in the insulin secretory response as well, and the melatonin signal may play a part in its regulation. This paper addresses the involvement of the second messengers IP3 and intracellular Ca2+ ([Ca2+](i)) in the signalling cascade of melatonin in the rat insulinoma INS1 cell, a model for the pancreatic beta-cell. For this purpose melatonin at concentrations ranging from 1 to 100 nmol/L, carbachol and the nonselective melatonin receptor antagonist luzindole were used to stimulate INS1 cell batches, followed by an IP3-mass assay and Ca2+ imaging. Molecular biological studies relating to the mRNA of IP3 receptor (IP3R) subtypes and their relative abundance in INS1 cells showed expression of IP3R-1, IP3R-2 and IP3R-3 mRNA. In conclusion, we found that in rat insulinoma INS1 cells there is a dose-dependent stimulation of IP3 release by melatonin, which is accompanied by a likewise transient increase in [Ca2+](i) concentrations. The melatonin effect observed mimics carbachol action. It can be abolished by 30 mu mol/L luzindole and is sustained in Ca2+-free medium, suggesting a mechanism that includes the depletion of Ca2+ from intracellular stores.
引用
收藏
页码:316 / 323
页数:8
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