Rezvani A, Stokes K B, Rhoads D L, Way E L
Alcohol Drug Res. 1987;7(3):135-46.
Recently, it was reported that proglumide, a cholecystokinin (CCK) antagonist, potentiates the analgetic effects of morphine and endogenous opioid peptides and reverses morphine tolerance by antagonizing the CCK system in the central nervous system of the rat. In order to provide additional insight into the mode of action of this agent, we assessed the effect of proglumide in the isolated guinea pig ileum and the mouse, rat and rabbit vas deferens. Furthermore, we studied the in vitro binding affinity of this substance to mouse brain synaptosomes. Our results show that proglumide inhibits, dose dependently, the electrically stimulated twitches in the mouse vas deferens and guinea pig ileum, but not in the rat or rabbit vas deferens. The inhibitory action of proglumide on the mouse vas deferens, but not on the guinea pig ileum, is antagonized by naloxone and by the selective delta-antagonist, ICI 174,864, in a competitive fashion. Other CCK antagonists were found to be devoid of such activity on the mouse vas deferens. In vitro binding studies showed that proglumide displaces D-ala-D-[leucine]5-enkephalin (DADLE), a delta agonist, but not ethylketocyclazocine (EKC), a preferentially selective kappa agonist. The effect of proglumide appeared to be elicited presynaptically since it did not alter the norepinephrine-induced contractions of the mouse vas deferens. Our results suggest that proglumide might exert its opiate-like effects by activation of delta-opioid receptors.
最近有报道称，胆囊收缩素（CCK）拮抗剂丙谷胺可增强吗啡和内源性阿片肽的镇痛作用，并通过拮抗大鼠中枢神经系统中的CCK系统来逆转吗啡耐受性。为了更深入了解该药物的作用方式，我们评估了丙谷胺对离体豚鼠回肠以及小鼠、大鼠和兔输精管的作用。此外，我们研究了该物质与小鼠脑突触体的体外结合亲和力。我们的结果表明，丙谷胺剂量依赖性地抑制小鼠输精管和豚鼠回肠的电刺激抽搐，但对大鼠或兔输精管无此作用。丙谷胺对小鼠输精管而非豚鼠回肠的抑制作用可被纳洛酮和选择性δ拮抗剂ICI 174,864以竞争性方式拮抗。其他CCK拮抗剂对小鼠输精管无此类活性。体外结合研究表明，丙谷胺可置换δ激动剂D-丙氨酰-D-[亮氨酸]5-脑啡肽（DADLE），但不能置换优先选择性κ激动剂乙基酮环唑辛（EKC）。丙谷胺的作用似乎是在突触前引发的，因为它并未改变去甲肾上腺素诱导的小鼠输精管收缩。我们的结果表明，丙谷胺可能通过激活δ阿片受体发挥其类阿片样作用。
