Zhu X G, Greeley G H, Lewis B G, Lilja P, Thompson J C
J Neurosci Res. 1986;15(3):393-403. doi: 10.1002/jnr.490150310.
The purpose of this study, in part, was to determine the ability of cholecystokinin (CCK-33/39 and CCK-8) to penetrate the blood cerebrospinal fluid (CSF) barrier in dogs by measuring these forms of CCK in plasma and in CSF. In addition, the effectiveness of centrally administered bombesin in releasing brain CCK-33/39 and CCK-8 was evaluated. Six groups of five dogs each were studied. Each group received one of the following: (1) intravenous infusion of CCK-33/39 (1.3 micrograms/kg/hr); (2) intravenous infusion of CCK-8 (0.4 micrograms/kg/hr); (3) intrathecal infusion of CCK-33/39 (1.3 micrograms/kg/hr); (4) intrathecal infusion of CCK-8 (0.5 micrograms/kg/hr); (5) intravenous infusion of bombesin (1 micrograms/kg/hr); and (6) intrathecal infusion of bombesin (1 microgram/kg/hr). Plasma concentrations of CCK-33/39 significantly increased during intravenous infusion of CCK-33/39 (from basal of 84 +/- 8 to 142 +/- 2 pg/ml) or bombesin (from basal of 78 +/- 13 to 325 +/- 87 pg/ml); however, CSF perfusate concentrations of CCK-33/39 did not increase. CCK-33/39 levels of the CSF perfusate increased significantly (P less than .05) from 211 +/- 84 to 9,873 +/- 3,368 pg/ml during intrathecal infusion of CCK-33/39, but failed to rise simultaneously in the systemic circulation. Similarly, intravenous infusion of CCK-8 caused a fivefold elevation in plasma CCK-8 levels and no change in CSF perfusate levels of CCK-8; moreover, intrathecal infusion of CCK-8 failed to elevate peripheral CCK-8 levels, despite CSF perfusate CCK-8 levels of 92,300 +/- 18,598 pg/ml. Intrathecal concentrations of neither CCK-33 nor CCK-8 were affected by intravenous or intrathecal administration of bombesin. We conclude that CCK-33/39 and CCK-8 do not penetrate the blood-cerebrospinal fluid barrier in dogs, and centrally administered bombesin is ineffective in causing release of cholecystokinin from brain tissue into the CSF.
本研究的部分目的是通过测量犬血浆和脑脊液中这些形式的胆囊收缩素（CCK - 33/39和CCK - 8），来确定其穿透血脑脊髓液（CSF）屏障的能力。此外，还评估了脑室内注射蛙皮素释放脑CCK - 33/39和CCK - 8的效果。对六组犬进行了研究，每组五只。每组接受以下处理之一：（1）静脉输注CCK - 33/39（1.3微克/千克/小时）；（2）静脉输注CCK - 8（0.4微克/千克/小时）；（3）鞘内输注CCK - 33/39（1.3微克/千克/小时）；（4）鞘内输注CCK - 8（0.5微克/千克/小时）；（5）静脉输注蛙皮素（1微克/千克/小时）；（6）鞘内输注蛙皮素（1微克/千克/小时）。静脉输注CCK - 33/39（从基础值84±8升高至142±2皮克/毫升）或蛙皮素（从基础值78±13升高至325±87皮克/毫升）期间，血浆CCK - 33/39浓度显著升高；然而，脑脊液灌流液中CCK - 33/39浓度并未升高。鞘内输注CCK - 33/39期间，脑脊液灌流液中CCK - 33/39水平从211±84显著升高至9873±3368皮克/毫升（P＜0.05），但全身循环中未同时升高。同样，静脉输注CCK - 8使血浆CCK - 8水平升高五倍，而脑脊液灌流液中CCK - 8水平无变化；此外，鞘内输注CCK - 8未能升高外周CCK - 8水平，尽管脑脊液灌流液中CCK - 8水平为92300±18598皮克/毫升。静脉或鞘内注射蛙皮素均不影响鞘内CCK - 33和CCK - 8的浓度。我们得出结论，CCK - 33/39和CCK - 8不能穿透犬的血脑脊髓液屏障，且脑室内注射蛙皮素不能有效促使脑组织中的胆囊收缩素释放到脑脊液中。
