Tozawa Y, Ueki A, Shimosawa T, Fujita T
The Fourth Department of Internal Medicine, School of Medicine, University of Tokyo, Japan.
Biochem Pharmacol. 1999 Oct 15;58(8):1329-34. doi: 10.1016/s0006-2952(99)00195-1.
Isatin, a stress-related biological substance, increases in rat urine in association with elevated catecholamine biosynthesis during stress. The goal of this study was to unravel how the biosynthetic pathway of isatin is related to stress response. The importance of the serotonergic compounds in anxiety, which is the major emotional process of stress response, has emerged. m-Chlorophenylpiperazine (m-CPP), a 5-HT(1A/1B/2A/2C) receptor agonist, and (+/-)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane hydrochloride [(+/-)-DOI], a 5-HT(2A/2C) agonist, both of which have anxiogenic properties, induced a marked increase in 24-hr urinary isatin excretion, whereas neither 1-(m-chlorophenyl)-biguanide (m-CPBG), a 5-HT3 agonist, nor 2-methyl-5-HT, a 5-HT(3,4) agonist, affected urinary isatin excretion. 5-HT(2A/2C) receptor antagonists such as ketanserin and ritanserin prevented the increase in urinary isatin excretion induced by the 5-HT(2A/2C) receptor agonist m-CPP. These findings are the first to provide evidence that pharmacological substances cause increases in urinary isatin excretion via specific 5-HT receptors, probably 5-HT(2A/2C) receptors. In addition, both the synthetic glucocorticoid dexamethasone and diazepam prevented the m-CPP-induced increase in urinary isatin excretion. These observations suggest that the mechanism by which m-CPP elicits enhancing effects on urinary isatin excretion has something in common with stress response involving activation of hypothalamic CRF cells and the sympathetic nervous system.
异吲哚酮是一种与应激相关的生物物质，在应激过程中，随着儿茶酚胺生物合成的增加，大鼠尿液中的异吲哚酮含量也会升高。本研究的目的是揭示异吲哚酮的生物合成途径与应激反应之间的关系。血清素能化合物在焦虑（应激反应的主要情绪过程）中的重要性已逐渐显现。间氯苯哌嗪（m-CPP）是一种5-HT(1A/1B/2A/2C)受体激动剂，（±）-1-（4-碘-2,5-二甲氧基苯基）-2-氨基丙烷盐酸盐[（±）-DOI]是一种5-HT(2A/2C)激动剂，二者均具有致焦虑特性，它们均可使24小时尿异吲哚酮排泄量显著增加，而5-HT3激动剂1-（间氯苯基）-双胍（m-CPBG）和5-HT(3,4)激动剂2-甲基-5-HT均不影响尿异吲哚酮排泄。5-HT(2A/2C)受体拮抗剂如酮色林和利坦色林可阻止5-HT(2A/2C)受体激动剂m-CPP诱导的尿异吲哚酮排泄增加。这些发现首次提供证据表明，药理物质可通过特定的5-HT受体（可能是5-HT(2A/2C)受体）导致尿异吲哚酮排泄增加。此外，合成糖皮质激素地塞米松和地西泮均可阻止m-CPP诱导的尿异吲哚酮排泄增加。这些观察结果表明，m-CPP引起尿异吲哚酮排泄增强效应的机制与涉及下丘脑CRF细胞和交感神经系统激活的应激反应有共同之处。
