Hernandez D E, Stanley D A, Melvin J A, Prange A J
Pharmacol Biochem Behav. 1985 Apr;22(4):509-13. doi: 10.1016/0091-3057(85)90266-7.
We have reported previously that intracisternal (IC) administration of neurotensin (NT) prevents stress-induced gastric ulcers in rats. This effect of NT appears to be mediated by the central nervous system because peripheral (IV) NT is totally ineffective. The present study sought to clarify the central mechanism of the cytoprotective effect of NT by utilizing pharmacological treatments which alter the function of brain neurotransmitter systems. Pretreatment with intracerebroventricular (ICV) administration of agonists and antagonists of acetylcholine (ACh), gamma-aminobutyric acid (GABA), and serotonin (5-HT) receptors or with an anti-opiate (naloxone) agent did not significantly alter NT-induced cytoprotection. However, pretreatment with ICV haloperidol, a dopamine (DA) receptor antagonist, totally blocked NT's cytoprotective effect. In addition, pretreatment with methylphenidate, a DA receptor agonist, produced cytoprotection similar to IC NT. These data indicate that NT-induced cytoprotection is not mediated by 5-HT, GABA, ACh (muscarinic) receptors, or endogenous opiate systems, but suggest interactions between brain DA systems and NT.
我们之前报道过，脑池内（IC）注射神经降压素（NT）可预防大鼠应激诱导的胃溃疡。NT的这种作用似乎是由中枢神经系统介导的，因为外周（静脉注射）NT完全无效。本研究试图通过利用改变脑神经递质系统功能的药理学治疗方法来阐明NT细胞保护作用的中枢机制。脑室内（ICV）注射乙酰胆碱（ACh）、γ-氨基丁酸（GABA）和5-羟色胺（5-HT）受体的激动剂和拮抗剂或抗阿片类（纳洛酮）药物进行预处理，并没有显著改变NT诱导的细胞保护作用。然而，用多巴胺（DA）受体拮抗剂氟哌啶醇进行ICV预处理，完全阻断了NT的细胞保护作用。此外，用DA受体激动剂哌甲酯进行预处理，产生了与IC NT相似的细胞保护作用。这些数据表明，NT诱导的细胞保护作用不是由5-HT、GABA、ACh（毒蕈碱）受体或内源性阿片系统介导的，但提示脑DA系统与NT之间存在相互作用。
