Ambrose F G, Barbaz B S, Autry W L, Browne R G, Liebman J M
Research Department, CIBA-GEIGY Corporation, Summit, NJ 07901.
Peptides. 1989 Jan-Feb;10(1):31-4. doi: 10.1016/0196-9781(89)90071-5.
Previous studies have shown that unsulfated cholecystokinin octapeptide (CCK-8-U) shares with the sulfated octapeptide (CCK-8-S) and the carboxyl-terminal tetrapeptide (CCK-4) the ability to block abdominal irritant-induced stretching when administered intracerebroventricularly. The effects of CCK-8-U, however, are not naloxone-reversible and do not appear upon systemic administration. To assess the hypothesis that the antistretching effects of CCK-8-U are mediated by central-type (CCK-B), rather than peripheral-type (CCK-A) receptors, the present experiments examined the reversal of these effects by CR 1409, a CCK receptor antagonist with in vitro selectivity for CCK-A receptors, and by proglumide. Both antagonists, when administered ICV, blocked the antistretching effects of CCK-8-S and CCK-4 (ICV), but not those of CCK-8-U. CR 1409 was approximately 40 times more potent against CCK-8-S by the ICV route than subcutaneously, indicating a likely action on CCK-A receptors in the brain. The effects of morphine, bombesin and neurotensin (ICV) were not blocked by CR 1409, indicating specificity for CCK receptor-mediated effects. The antistretching effects of CCK-8-U do not appear to be mediated by CCK-A receptors, and the possibility of a CCK-B receptor site of action must be considered.
先前的研究表明，未硫酸化的胆囊收缩素八肽（CCK-8-U）与硫酸化八肽（CCK-8-S）以及羧基末端四肽（CCK-4）一样，在脑室内给药时具有阻断腹部刺激诱导的伸展的能力。然而，CCK-8-U的作用不能被纳洛酮逆转，且全身给药时不出现该作用。为了评估CCK-8-U的抗伸展作用是由中枢型（CCK-B）而非外周型（CCK-A）受体介导的这一假说，本实验研究了CCK受体拮抗剂CR 1409（一种对CCK-A受体具有体外选择性的拮抗剂）和丙谷胺对这些作用的逆转情况。两种拮抗剂脑室内给药时，均可阻断CCK-8-S和CCK-4（脑室内给药）的抗伸展作用，但不能阻断CCK-8-U的抗伸展作用。CR 1409经脑室内给药途径对CCK-8-S的效力比对皮下给药强约40倍，表明其可能作用于脑内的CCK-A受体。CR 1409不能阻断吗啡、蛙皮素和神经降压素（脑室内给药）的作用，表明其对CCK受体介导的作用具有特异性。CCK-8-U的抗伸展作用似乎不是由CCK-A受体介导的，因此必须考虑其作用于CCK-B受体位点的可能性。
