JMV 236, a new cholecystokinin-octapeptide-sulfate (CCK 8 S) derivative (Boc-Tyr (SO3)-Nle-Gly-Trp-Nle-Asp-Phe-NH2) has been synthesized in the Centre de Pharmacologie-Endocrinologie (Montpellier). This peptide has been shown to present the same activity as CCK 8 S on pancreatic amylase secretion and has the advantage of a better chemical stability. With a view to further characterization, the effect of JMV 236 on food intake and brain monoamine and metabolite variations was assayed in the rat after intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) administrations. JMV 236 decreased food intake 2 and 3 hours after i.p. administration of 12.5 and 50 micrograms/kg but was inactive after i.c.v. injection. Its global action was similar to that of CCK 8 S, but was less marked with delayed onset of response. As in our previous work with CCK 8 S, JMV 236 was more potent in inducing monoaminergic variations after i.p. than after i.c.v. administration. The main effects were decreases in striatal dopamine metabolite levels and increases in hypothalamic and striatal serotonin metabolite (5-HIAA) levels. These effects are classically observed with CCK 8 S and are described in our previous reports. The interesting peptide will require further characterization and may serve as a possible reference compound for studies on CCK derivatives.

译文

JMV 236,一种新的胆囊收缩素-八肽-硫酸盐 (CCK 8 S) 衍生物 (Boc-Tyr (SO3)-Nle-Gly-Trp-Nle-Asp-Phe-NH2) 已在药物内分泌中心 (蒙彼利埃) 合成。已显示该肽在胰腺淀粉酶分泌上具有与CCK 8 s相同的活性,并且具有更好的化学稳定性的优势。为了进一步表征,在腹膜内 (i.p.) 和脑室内 (i.c.v.) 给药后,在大鼠中测定了JMV 236对食物摄入以及脑单胺和代谢物变化的影响。静脉注射后2小时和3小时,JMV 236降低了食物摄入量。施用12.5和50微克/千克,但在静脉注射后无效。它的全局作用与CCK 8 s相似,但反应延迟发作的特征较小。与我们先前使用CCK 8 s的工作一样,JMV 236在i.p.之后更有效地诱导单胺能变化。比i.c.v.管理后还要多。主要影响是纹状体多巴胺代谢物水平降低,下丘脑和纹状体5-羟色胺代谢物 (5-HIAA) 水平升高。这些影响在CCK 8 s中经典观察到,并在我们之前的报告中进行了描述。该有趣的肽将需要进一步的表征,并且可以作为CCK衍生物研究的可能参考化合物。

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