Cholecystokinin receptor-1 mediates the inhibitory effects of exogenous cholecystokinin octapeptide on cellular morphine dependence
<p>Abstract</p> <p>Background</p> <p>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 wi...
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| Format: | Article |
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BMC
2012-06-01
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| Series: | BMC Neuroscience |
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| Online Access: | http://www.biomedcentral.com/1471-2202/13/63 |
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| author | Wen Di Ma Chun-ling Zhang Ya-jing Meng Yan-xin Ni Zhi-yu Li Shu-jin Cong Bin |
| author_facet | Wen Di Ma Chun-ling Zhang Ya-jing Meng Yan-xin Ni Zhi-yu Li Shu-jin Cong Bin |
| author_sort | Wen Di |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>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.</p> |
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| spelling | doaj.art-0b5daf42742c46c4a26371d0b3812d1b2022-12-21T19:59:32ZengBMCBMC Neuroscience1471-22022012-06-011316310.1186/1471-2202-13-63Cholecystokinin receptor-1 mediates the inhibitory effects of exogenous cholecystokinin octapeptide on cellular morphine dependenceWen DiMa Chun-lingZhang Ya-jingMeng Yan-xinNi Zhi-yuLi Shu-jinCong Bin<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>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.</p>http://www.biomedcentral.com/1471-2202/13/63Cholecystokinin octapeptideCCK1 receptorCCK2 receptorMorphineCellular dependencecAMP overshoot |
| spellingShingle | Wen Di Ma Chun-ling Zhang Ya-jing Meng Yan-xin Ni Zhi-yu Li Shu-jin Cong Bin Cholecystokinin receptor-1 mediates the inhibitory effects of exogenous cholecystokinin octapeptide on cellular morphine dependence BMC Neuroscience Cholecystokinin octapeptide CCK1 receptor CCK2 receptor Morphine Cellular dependence cAMP overshoot |
| title | Cholecystokinin receptor-1 mediates the inhibitory effects of exogenous cholecystokinin octapeptide on cellular morphine dependence |
| title_full | Cholecystokinin receptor-1 mediates the inhibitory effects of exogenous cholecystokinin octapeptide on cellular morphine dependence |
| title_fullStr | Cholecystokinin receptor-1 mediates the inhibitory effects of exogenous cholecystokinin octapeptide on cellular morphine dependence |
| title_full_unstemmed | Cholecystokinin receptor-1 mediates the inhibitory effects of exogenous cholecystokinin octapeptide on cellular morphine dependence |
| title_short | Cholecystokinin receptor-1 mediates the inhibitory effects of exogenous cholecystokinin octapeptide on cellular morphine dependence |
| title_sort | cholecystokinin receptor 1 mediates the inhibitory effects of exogenous cholecystokinin octapeptide on cellular morphine dependence |
| topic | Cholecystokinin octapeptide CCK1 receptor CCK2 receptor Morphine Cellular dependence cAMP overshoot |
| url | http://www.biomedcentral.com/1471-2202/13/63 |
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