CCK Octapeptide is a rapid-acting, synthetic analog of cholecystokinin which exist both in the central nervous system (CNS) and in the gastrointestinal tract. CCK Octapeptide accelerates the contraction of the gall bladder to release bile and promote food digestion, yet it reduces the entire digestive function by suppressing feeding behavior after its central administration. In relation to pain and analgesia, CCK Octapeptide antagonizes opioid analgesia at a lower dose[1][2].
In vitro, in isolated rat pancreatic acinar cells,CCK Octapeptide(0.01 to 5nM) or secretin (2.5 to 500nM) was added directly to the incubation medium and cultured for 30min. CCK Octapeptide was found to be more efficient compared to secretin in stimulating amylase release. A combination of secretin and CCK Octapeptide had a synergistic action in stimulating enzyme release by the acinar cells[3]. Human peripheral-blood neutrophils were incubated with CCK Octapeptide (10⁻14 to 10⁻6M) for 10min, 60min or 2h. CCK Octapeptide increased the adherence capacity and decreased the spontaneous mobility capacity of neutrophils. CCK Octapeptide also decreased the neutrophil ingestion capacity since it had an inhibitory effect on the latex bead phagocytosis by human neutrophils[4].
In vivo, delayed neurocognitive recovery (dNCR) mice model received a single intraperitoneal injection of CCK Octapeptide (1.6μg/kg) after laparotomy once daily from day 0 to day 7. CCK Octapeptide alleviated cognitive impairment and promoted glutamatergic synaptogenesis by inhibiting the induction of A1 reactive astrocytes and the activation of microglia[5]. Wistar male rats received morphine treatments for 5 consecutive days followed by saline injections to induce morphine withdrawal. On day 10 (5 days after the induction of morphine dependence), the rats received injections of three different doses of CCK Octapeptide (0.01, 0.1, and 1μg; i.c.v.). Administration of CCK Octapeptide before elevated plus-maze (EPM) testing decreased anxiety-like behavior in a dose-dependent fashion in morphine-withdrawal rats via CCK1 receptor activation and endogenous opioid peptides upregulation[6]. CCK Octapeptide was administered intraperitoneally (i.p.) at a single dose of 95 or 190ng per 100g body weight in a volume of 0.1ml/100g into adult male Wistar rats. Animals were sacrificed 30min post-injection. CCK Octapeptide produced no significant rise in plasma corticosterone levels[7].
References:
[1] Maher KA et al. Kinevac (sincalide for injection)/Squibb Diagnostics. Gastroenterol Nurs. 1991 Oct;14(2):98-100.
[2] Han J S, Ding X Z, Fan S G. Cholecystokinin octapeptide (CCK-8): antagonism to electroacupuncture analgesia and a possible role in electroacupuncture tolerance. Pain. 1986 Oct;27(1):101-115.
[3] Lee P C. Effect of CCK-octapeptide and secretin on amylase secretion in isolated rat pancreatic acinar cells. Digestion. 1979;19(1):6-14.
[4] Carrasco M, Del Rio M , Hernanz A, De la Fuente M. Inhibition of human neutrophil functions by sulfated and nonsulfated cholecystokinin octapeptides. Peptides. 1997;18(3):415-22
[5] Chen L, Yang N, Li Y, et al. Cholecystokinin octapeptide improves hippocampal glutamatergic synaptogenesis and postoperative cognition by inhibiting induction of A1 reactive astrocytes in aged mice. CNS Neurosci Ther. 2021 Nov;27(11):1374-1384.
[6] Wen D, Sun D, Zang G, et al. Cholecystokinin octapeptide induces endogenous opioid-dependent anxiolytic effects in morphine-withdrawal rats. Neuroscience. 2014 Sep 26:277:14-25.
[7]Itoh S, Hirota R, Katsuura G. Effect of cholecystokinin octapeptide and vasoactive intestinal polypeptide on adrenocortical secretion in the rat. Jpn J Physiol. 1982;32(4):553-60.
CCK Octapeptide是一种快速起效的胆囊收缩素合成类似物，存在于中枢神经系统和胃肠道。CCK Octapeptide加速胆囊收缩以释放胆汁并促进食物消化，然而经中枢给药后通过抑制摄食行为而降低整体消化功能。在疼痛与镇痛方面，CCK Octapeptide在低剂量下可拮抗阿片镇痛作用[1][2]。
体外实验中，在分离的大鼠胰腺腺泡细胞中，将CCK Octapeptide(0.01–5nM)或secretin(2.5–500nM)直接加入孵育液并培养30min。CCK Octapeptide在刺激淀粉酶释放方面比secretin更有效；secretin与CCK Octapeptide联合使用对腺泡细胞酶释放具有协同作用[3]。人类外周血中性粒细胞与CCK Octapeptide(10⁻¹⁴–10⁻⁶M)孵育10min、60min或2h，CCK Octapeptide增加其黏附能力并降低自发运动能力；CCK Octapeptide抑制乳胶珠吞噬，从而降低中性粒细胞的摄取能力[4]。
体内实验中，术后认知恢复延迟(dNCR)小鼠模型于剖腹术后立即单次腹腔注射CCK Octapeptide(1.6μg/kg)，从手术当天（day 0）至 day 7连续给药，每日一次。CCK Octapeptide缓解认知障碍并通过抑制A1反应性星形胶质细胞的诱导及小胶质细胞的激活促进谷氨酸能突触形成[5]。Wistar雄性大鼠连续5天接受吗啡处理后以生理盐水诱导吗啡戒断。于戒断第10天(吗啡依赖诱导后第5天)脑室内注射三种剂量CCK Octapeptide(0.01、0.1、1μg)。在进行十字迷宫(EPM)测试前给予CCK Octapeptide，通过CCK1受体激活及内源性阿片肽上调剂量依赖性地减轻吗啡戒断大鼠的焦虑样行为[6]。CCK Octapeptide以95或190ng/100g体重的单次剂量腹腔注射(i.p.)于成年雄性Wistar大鼠，体积为0.1ml/100g；注射后30min处死动物，结果显示CCK Octapeptide未显著升高血浆皮质酮水平[7]。