The Roles of Lysophospholipids in Modulating the Intracellular Calcium Concentration in Bovine Chromaffin Cell

水解磷酸酯對牛腎上腺髓質細胞內鈣離子調控之研究

陳加林(Chia-Lin Chen) ； 潘建源(Chien-Yuan Pan)

《Acta Zoologica Taiwanica》 14卷2期 (2004/10) Pp. 147-148

https://doi.org/10.6576/AZT.2004.14.(2).29

摘要

Sphingosine-1-phosphate(S1P)和Lysophosphatidic acid (LPA)兩種水解磷酸酯在發炎反應時在血液中濃度會顯著上升，對血管新生與內皮細胞的分化、增生等皆扮演重要的角色。目前已知在神經細胞及神經膠細胞上，S1P和LPA都會造成細胞內鈣離子濃度上升，但其訊息傳導機制仍不清楚。在本實驗中發現，這兩種水解磷酸酯都可造成牛腎上腺髓質嗜鉻細胞[Ca(上標 2+)]i顯著上升，且劑量－反應關係有一飽和現象。此反應可被Thapsigargin抑制，顯示在S1P和LPA刺激下，細胞內鈣庫爲[Ca(上標 2+)]i上升的重要來源。爲進一步瞭解S1P和LPA的作用途徑，我們以各種藥物來處理細胞，以探討其作用機轉的差異。U73122和2-APB抑制兩者所造成的[Ca(上標 2+)]i上升，顯示Gq-PLC途徑的參與。而Pertussis toxin亦會抑制[Ca(上標 2+)]i上升，顯示Gi也參與反應。當以Ryanodine及DMS處理時，則只有S1P所引起的[Ca(上標 2+)]i上升受到明顯的抑制。這些結果顯示S1P和LPA主要都是經由活化Gq-PLC途徑，造成胞內鈣庫釋出鈣離子；而S1P還會間接活化ER上的Ryanodine受器，以釋出更多的鈣離子。

關鍵字

水解磷酸酯 ； 嗜鉻細胞 ； Sphingosine-1-phosphate S1P ； Lysophosphatidic acid LPA ； Ryanodine ； DMS

並列摘要

Sphingosine-1-phosphate (S1P) and lysophosphatidic acid (LPA) are two important Lysophospholipids in regulating multiple aspects of angiogenesis, endothelium differentiation and proliferation. During Inflammation, the concentration of S1P and LPA in plasma may increase to μM level. Some reports suggested that S1P and LPA could increase the [Ca(superscript 2+)]i in neurons and glia cells. However, the mechanism is not clear. Our results showed that both S1P and LPA could elevate [Ca(superscript 2+)]i in bovine chromaffin cells in a dose-dependent relationship. Thapsigargin pretreatment could eliminate the [Ca(superscript 2+)]i rising. Both U73122 and 2-APB inhibited S1P and LPA responses implied the involvement of Gq-PLC pathway; pertussis toxin inhibiting effect indicated the involvement of Gi pathway. Ryanodine and DMS had no significant inhibition effects in LPA response, but could inhibit the S1P elicited [Ca(superscript 2+)]i elevation. These suggest that S1P and LPA could increase [Ca(superscript 2+)]i by activating Gq-PLC and Gi pathways. Furthermore, S1P may somehow activate the Ryanodine receptor to release more calcium. Our result showed that S1P and LPA may work differently in modulating the stimulus-secretion coupling in bovine chromaffin cell.

並列關鍵字

Lysophospholipid ； chromaffin cell ； Sphingosine-1-phosphate S1P ； Lysophosphatidic acid LPA ； Ryanodine ； DMS