GM1神经节苷脂对表皮生长因子诱导的胃黏膜钙通道激活的调节作用

GM1-ganglioside regulation of EGF-induced gastric mucosal calcium channel activation.

Slomiany B L, Liu J, Yao P, Slomiany A

Research Center, New Jersey Dental School, University of Medicine and Dentistry of New Jersey, Newark 07103-2400.

Gen Pharmacol. 1992 Sep;23(5):799-803. doi: 10.1016/0306-3623(92)90227-b.

Abstract

Calcium channels, isolated from gastric epithelial cell membranes when reconstituted into phosphatidylcholine vesicles exhibited active 45Ca2+ uptake as evidenced by a dose dependent response to calcium channel activator, BAY K8644, and antagonist, PN200-110. 2. The channels on epidermal growth factor (EGF) binding in the presence of ATP showed an increase in tyrosine phosphorylation of 55 and 170 kDa calcium channel proteins. Such phosphorylated channels following reconstitution into the vesicles displayed a 48% greater 45Ca2+ uptake than that of the controls. 3. The binding of EGF to calcium channel protein was inhibited by GM1-ganglioside reaching maximum inhibition of 65% at 40 nM GM1. In contrast, calcium channel antagonist, PN200-110, had no effect on EGF binding. 4. The EGF-stimulated calcium channel protein phosphorylation was inhibited by GM1. This inhibitory effect was mainly reflected in the decrease of tyrosine phosphorylation of 55 and 170 kDa proteins. 5. The results suggest the participation of GM1-ganglioside in the regulation of EGF-stimulated gastric mucosal calcium channel activation.

摘要

从胃上皮细胞膜分离出的钙通道，重构于磷脂酰胆碱囊泡中时，对钙通道激活剂BAY K8644和拮抗剂PN200 - 110呈剂量依赖性反应，证明其具有活跃的45Ca2+摄取能力。2. 在ATP存在的情况下，表皮生长因子（EGF）结合后，55 kDa和170 kDa钙通道蛋白的酪氨酸磷酸化增加。重构于囊泡中的这种磷酸化通道显示出比对照高48%的45Ca2+摄取。3. GM1 - 神经节苷脂抑制EGF与钙通道蛋白的结合，在40 nM GM1时达到65%的最大抑制。相反，钙通道拮抗剂PN200 - 110对EGF结合无影响。4. GM1抑制EGF刺激的钙通道蛋白磷酸化。这种抑制作用主要体现在55 kDa和170 kDa蛋白酪氨酸磷酸化的减少。5. 结果表明GM1 - 神经节苷脂参与了EGF刺激的胃黏膜钙通道激活的调节。