Orosco M, Gourch A, Rodriguez M, Martinez J, Jacquot C, Cohen Y
Laboratoire de Pharmacologie, URA-CNRS 594, Faculté de Pharmacie, Chatenay Malabry, France.
Peptides. 1990 Sep-Oct;11(5):873-7. doi: 10.1016/0196-9781(90)90001-l.
Two analogues of the C-terminal heptapeptide of cholecystokinin have been synthesized, in which the C-terminal phenylalanine residue has been replaced by a phenylethylester (JMV 180) or a phenylethylamide (JMV 170) group. They have been shown to present partial agonist CCK activity on pancreatic amylase release. In this study, the effects of the two peptides were investigated on food intake and brain monoamine metabolism after intraperitoneal (IP) and intracerebroventricular (ICV) administration. Neither peptide was active on feeding after IP administration but both decreased food intake after ICV injection, with a slightly higher potency for JMV 170. JMV 180 induced no change in monoamine metabolism whatever the route of administration. JMV 170 IP decreased cortical levels of dopamine and its metabolites. This effect was stronger after ICV injection and was accompanied by changes in serotonergic metabolism in the hypothalamus and cortex. Contrary to CCK8 S, which is more active on feeding after peripheral injection, the feeding effects of the analogues obtained by modification of the C-terminal phenylalanine residue appear to involve a central site of action. Furthermore, phenylethylamide substitution (JMV 170) gives rise to greater potency on monoaminergic variations than replacement with a phenylethylester (JMV 180) and the effect is enhanced following central administration.
已合成胆囊收缩素C末端七肽的两种类似物，其中C末端苯丙氨酸残基已被苯乙酯（JMV 180）或苯乙酰胺（JMV 170）基团取代。它们已被证明在胰腺淀粉酶释放方面具有部分激动剂CCK活性。在本研究中，研究了这两种肽经腹腔注射（IP）和脑室内注射（ICV）后对食物摄入和脑单胺代谢的影响。腹腔注射后两种肽对进食均无活性，但脑室内注射后两者均降低食物摄入量，JMV 170的效力略高。无论给药途径如何，JMV 180均未引起单胺代谢变化。腹腔注射JMV 170可降低皮质中多巴胺及其代谢物的水平。脑室内注射后这种作用更强，并伴有下丘脑和皮质中血清素能代谢的变化。与外周注射后对进食更具活性的CCK8 S相反，通过修饰C末端苯丙氨酸残基获得的类似物的进食作用似乎涉及一个中枢作用部位。此外，苯乙酰胺取代（JMV 170）比用苯乙酯取代（JMV 180）对单胺能变化具有更大的效力，并且在中枢给药后作用增强。
