Calcium response after stimulation by Substance P of U373 MG cells: inhibition of store-operated calcium entry by protein kinase C

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• 作者：Maria Galiano ; Giuseppe Gasparre ; Claudio Lippe ; Giuseppe Cassano
• 关键词：Substance P ; Protein kinase C ; U373 MG cell
• 刊名：Cell Calcium
• 出版年：2004
• 出版时间：February 2004
• 年：2004
• 卷：35
• 期：2
• 页码：123-130
• 全文大小：172 K

文摘

In this paper we investigate the Ca²⁺ response after Substance P (SP) stimulation of U373 MG cells. SP is a tachykinin and physiologically acts as a neurotransmitter and neuromodulator in the nervous system, but pathologically triggers malignant glial cells, such as U373 MG, to release cytokines and increase proliferation rate.

In this paper we show that SP increases the proliferation rate of U373 MG cells and the intracellular Ca²⁺ concentration by mobilizing Ca²⁺ only from thapsigargin-sensitive stores. In fact, Ca²⁺ entry through store-operated calcium entry (SOCE) channels, which was observed after thapsigargin treatment, was not detected after stimulation by SP. The inhibition of SOCE after SP stimulation must be mediated by protein kinase C (PKC), because it was not observed in the presence of calphostin C (an inhibitor of PKC). Moreover, stimulation by SP-induced membrane potential hyperpolarization.

Our results are consistent with the following sequence of events: (i) SP interacts with NK₁ receptors; (ii) fast homologous receptor desensitization occurs; (iii) reuptake by endoplasmic reticulum Ca²⁺-ATPase quantitatively overwhelms the extrusion by plasma membrane Ca²⁺-ATPase. These results have two important consequences. In U373 MG cells the SOCE does not contribute to the Ca²⁺ response after SP, and is not necessarily involved in promoting cell proliferation.