Experimental Oncology Laboratory, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA.
Future Oncol. 2010 Feb;6(2):221-8. doi: 10.2217/fon.09.171.
Pancreatic ductal adenocarcinoma (PDAC) has a near 100% mortality because it is generally detected at an advanced stage and responds poorly to existing therapeutics. This review summarizes current evidence suggesting important roles of neurotransmitter receptors in the regulation of this malignancy. Experimental evidence indicates that the alpha(7)-nicotinic acetylcholine receptor (alpha(7)nAChR) stimulates PDAC via stress neurotransmitter-mediated activation of beta-adrenergic signaling while the alpha(4)beta(2)nAChR inhibits PDAC via GABA-mediated inhibition of adenylyl cyclase activation. In analogy to molecular mechanisms that govern nicotine addiction, chronic exposure to nicotine or its nitrosated derivative nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone render the stimulatory alpha(7)nAChR hyperactive while desensitizing the inhibitory alpha(4)beta(2)nAChR. Accordingly, PDAC intervention strategies should include the diagnosis of unphysiological neurotransmitter levels and aim to restore any imbalance in stimulatory and inhibitory neurotransmitters.
胰腺导管腺癌 (PDAC) 的死亡率接近 100%，因为它通常在晚期被发现，并且对现有治疗方法反应不佳。这篇综述总结了目前的证据，表明神经递质受体在调节这种恶性肿瘤方面起着重要作用。实验证据表明，α(7)-烟碱型乙酰胆碱受体 (α(7)nAChR) 通过应激神经递质介导的β-肾上腺素能信号激活刺激 PDAC，而α(4)β(2)nAChR 通过 GABA 介导的抑制腺苷酸环化酶激活来抑制 PDAC。类似于控制尼古丁成瘾的分子机制，慢性暴露于尼古丁或其亚硝化为亚硝胺 4-(甲基亚硝氨基)-1-(3-吡啶基)-1-丁酮会使刺激性的α(7)nAChR 过度活跃，同时使抑制性的α(4)β(2)nAChR 脱敏。因此，PDAC 的干预策略应包括诊断非生理性神经递质水平，并旨在恢复刺激和抑制性神经递质之间的任何失衡。
