Zheng X L, Hollenberg M D
Department of Pharmacology and Therapeutics, University of Calgary, Faculty of Medicine, Canada.
Proc Assoc Am Physicians. 1997 Jan;109(1):78-83.
We have evaluated the signal transduction pathways whereby, in comparison with epidermal growth factor-urogastrone, ethanol causes a rapid contractile response in guinea pig gastric longitudinal muscle. As for epidermal growth factor (EGF), the ethanol-induced contraction required extracellular calcium, was sensitive to the tyrosine kinase inhibitors genistein and tyrphostin 47 (AG213), and was blocked by both the cyclo-oxygenase inhibitor, indomethacin, and the diacylglycerol lipase inhibitor, U57908. The 50% effective concentration (EC50) for the contractile action of ethanol (approximately 140 mM) was lower than that for propanol and methanol and was not affected by the aldehyde dehydrogenase inhibitor, 4-methyl pyrazole. The actions of ethanol were distinct from those of EGF in that EGF-induced contractions were sensitive to the kinase C inhibitor GF109203X, and the EGF receptor kinase inhibitor PD153035, whereas ethanol-induced contractions were refractory to these inhibitors. Further, EGF-induced contractions were attenuated by the voltage-sensitive calcium channel antagonist, nifedipine, whereas the ethanol-induced contractile response was resistant to nifedipine but blocked by the "receptor-operated" calcium channel antagonist SKF96365. We conclude that ethanol without metabolism via alcohol dehydrogenase causes a contractile response in gastric longitudinal muscle tissue via a tyrosine kinase inhibitor-sensitive signal pathway that is parallel in many respects but yet is distinct from that activated by EGF.
我们已经评估了信号转导途径，通过该途径，与表皮生长因子-尿抑胃素相比，乙醇可在豚鼠胃纵肌中引起快速收缩反应。至于表皮生长因子（EGF），乙醇诱导的收缩需要细胞外钙，对酪氨酸激酶抑制剂染料木黄酮和 tyrphostin 47（AG213）敏感，并且被环氧化酶抑制剂吲哚美辛和二酰基甘油脂肪酶抑制剂U57908阻断。乙醇收缩作用的50%有效浓度（EC50）（约140 mM）低于丙醇和甲醇，且不受醛脱氢酶抑制剂4-甲基吡唑的影响。乙醇的作用与EGF不同，因为EGF诱导的收缩对蛋白激酶C抑制剂GF109203X和EGF受体激酶抑制剂PD153035敏感，而乙醇诱导的收缩对这些抑制剂不敏感。此外，EGF诱导的收缩被电压敏感性钙通道拮抗剂硝苯地平减弱，而乙醇诱导的收缩反应对硝苯地平有抗性，但被“受体操纵型”钙通道拮抗剂SKF96365阻断。我们得出结论，未经乙醇脱氢酶代谢的乙醇通过酪氨酸激酶抑制剂敏感的信号通路在胃纵肌组织中引起收缩反应，该信号通路在许多方面与EGF激活 的信号通路平行，但又有所不同。
