Journal Article

Cholecystokinin receptor-1 mediates the inhibitory effects of exogenous cholecystokinin octapeptide on cellular morphine dependence

Li, Shu-jin, Wen, Di, Zhang, Ya-jing, Ni, Zhi-yu, Cong, Bin, Ma, Chun-ling, Meng, Yan-xin

2012

Overview

Background Cholecystokinin octapeptide (CCK-8), the most potent endogenous anti-opioid peptide, has been shown to regulate the processes of morphine dependence. In our previous study, we found that exogenous CCK-8 attenuated naloxone induced withdrawal symptoms. To investigate the precise effect of exogenous CCK-8 and the role of cholecystokinin (CCK) 1 and/or 2 receptors in morphine dependence, a SH-SY5Y cell model was employed, in which the μ-opioid receptor, CCK1/2 receptors, and endogenous CCK are co-expressed. Results Forty-eight hours after treating SH-SY5Y cells with morphine (10 μM), naloxone (10 μM) induced a cAMP overshoot, indicating that cellular morphine dependence had been induced. The CCK receptor and endogenous CCK were up-regulated after chronic morphine exposure. The CCK2 receptor antagonist (LY-288,513) at 1–10 μM inhibited the naloxone-precipitated cAMP overshoot, but the CCK1 receptor antagonist (L-364,718) did not. Interestingly, CCK-8 (0.1-1 μM), a strong CCK receptor agonist, dose-dependently inhibited the naloxone-precipitated cAMP overshoot in SH-SY5Y cells when co-pretreated with morphine. The L-364,718 significantly blocked the inhibitory effect of exogenous CCK-8 on the cAMP overshoot at 1–10 μM, while the LY-288,513 did not. Therefore, the CCK2 receptor appears to be necessary for low concentrations of endogenous CCK to potentiate morphine dependence in SH-SY5Y cells. An additional inhibitory effect of CCK-8 at higher concentrations appears to involve the CCK1 receptor. Conclusions This study reveals the difference between exogenous CCK-8 and endogenous CCK effects on the development of morphine dependence, and provides the first evidence for the participation of the CCK1 receptor in the inhibitory effects of exogenous CCK-8 on morphine dependence.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Analysis / Analysis of Variance / Animal Models / Biomedical and Life Sciences / Biomedicine / cAMP overshoot / CCK1 receptor / CCK2 receptor / Cell Line, Tumor / Cellular dependence / Cholecystokinin / Cholecystokinin octapeptide / Cholecystokinin receptors / Colforsin - pharmacology / Cyclic adenylic acid / Cyclic AMP / Cyclic AMP - metabolism / Cytokine receptors / Dependence / Dose-Response Relationship, Drug / Drug abuse / Drug dosages / Drug withdrawal / Experiments / Forensic medicine / Hormone Antagonists - pharmacology / Humans / Morphine / Morphine - pharmacology / Morphine habit / Naloxone / Naloxone - pharmacology / Narcotic Antagonists - pharmacology / Narcotics / Narcotics - pharmacology / Neural networks / Neurobiology / Neuroblastoma / Neurosciences / Opioid receptors / Peptides / Physiological aspects / Receptor, Cholecystokinin A - genetics / Receptor, Cholecystokinin A - metabolism / Receptor, Cholecystokinin B - genetics / Receptor, Cholecystokinin B - metabolism / Receptors, Cholecystokinin - genetics / Receptors, Cholecystokinin - metabolism / Receptors, Opioid, mu - genetics / Receptors, Opioid, mu - metabolism / Research Article / RNA, Messenger / Sincalide - pharmacology / Up-Regulation - drug effects