DAMGO is a highly selective peptide agonist for the μ-opioid receptor (MOR) with a Kd of 3.46nM[1-2]. DAMGO activates G protein-coupled receptors, inhibits adenylate cyclase to reduce intracellular cAMP levels, and modulates ion channel activity, thereby suppressing neuronal excitability and neurotransmitter release. DAMGO can be used for pain mechanism research, neural signaling pathway analysis, and opioid receptor function studies[3-4].
In vitro, rat dorsal root ganglion sensory neurons were pretreated with DAMGO (1μM) for 2-3min, followed by stimulation with prostaglandin E₂ (PGE₂; 1μM) for 120s. DAMGO significantly inhibited PGE₂-induced enhancement of tetrodotoxin-resistant sodium currents (TTX-R Iₙₐ)[5]. TF-1 human bone marrow progenitor cells were pretreated with DAMGO (1μM and 10μM) for 24 hours. DAMGO reduced the expression level of the CXCR4 receptor on the cell surface and significantly inhibited the replication of the X4-tropic HIV-1 strain IIIB in cells[6].
In vivo, DAMGO (10ng) was stereotactically injected into the anterior cingulate cortex of young male mice (administered on postnatal days 6, 8, and 10). DAMGO induced autism-like behaviors in mice, including social interaction deficits, anxiety-like behaviors, and stereotyped behaviors, while downregulating Grin2b expression and GluN2B protein levels in the anterior cingulate cortex[7]. DAMGO (5–15μg) was administered via local (surgical site) or lumbar (L3–L5) intrathecal injection to adult (3–6 months old) and aged (24 months old) mice (administered on day 1 or days 1–3 postoperatively). DAMGO dose-dependently attenuated heat- and mechanical-induced postoperative hyperalgesia in an incision model. The inhibitory effect on incision-induced spontaneous pain by intrathecal DAMGO (5μg) or systemic intraperitoneal injection (1mg/kg) was more pronounced in adult mice[8].
References:
[1] Onogi T, Minami M, Katao Y, et al. DAMGO, a mu-opioid receptor selective agonist, distinguishes between mu- and delta-opioid receptors around their first extracellular loops. FEBS Lett. 1995 Jan 2;357(1):93-7.
[2] Eisenberg RM. DAMGO stimulates the hypothalamo-pituitary-adrenal axis through a mu-2 opioid receptor. J Pharmacol Exp Ther. 1993 Aug;266(2):985-91.
[3] Minami M, Onogi T, Nakagawa T, et al. DAMGO, a mu-opioid receptor selective ligand, distinguishes between mu-and kappa-opioid receptors at a different region from that for the distinction between mu- and delta-opioid receptors. FEBS Lett. 1995 May 1;364(1):23-7.
[4] Koganezawa T, Okada Y, Terui N, et al. A μ-opioid receptor agonist DAMGO induces rapid breathing in the arterially perfused in situ preparation of rat. Respir Physiol Neurobiol. 2011 Jul 31;177(2):207-11.
[5] Gold MS, Levine JD. DAMGO inhibits prostaglandin E2-induced potentiation of a TTX-resistant Na+ current in rat sensory neurons in vitro. Neurosci Lett. 1996 Jul 12;212(2):83-6.
[6] Strazza M, Banerjee A, Alexaki A, et al. Effect of μ-opioid agonist DAMGO on surface CXCR4 and HIV-1 replication in TF-1 human bone marrow progenitor cells. BMC Res Notes. 2014 Oct 23;7:752.
[7] Sheng Z, Liu Q, Cheng C, et al. Fentanyl induces autism-like behaviours in mice by hypermethylation of the glutamate receptor gene Grin2b. Br J Anaesth. 2022 Oct;129(4):544-554.
[8] Mecklenburg J, Patil MJ, Koek W, et al. Effects of local and spinal administrations of mu-opioids on postoperative pain in aged versus adult mice. Pain Rep. 2017 Jan;2(1):e584.
DAMGO是一种μ-阿片受体（MOR）的高选择性多肽激动剂（Kd=3.46nM）[1-2]。DAMGO通过激活G蛋白偶联受体，抑制腺苷酸环化酶以降低细胞内cAMP水平，并调节离子通道活性，从而抑制神经元兴奋性和神经递质释放。DAMGO可用于疼痛机制研究、神经信号通路分析及阿片受体功能研究[3-4]。
在体外，DAMGO（1μM）预处理大鼠背根神经节感觉神经元2-3min，随后应用前列腺素E₂（PGE₂；1μM）刺激120秒，DAMGO显著抑制PGE₂诱导的河豚毒素不敏感钠电流（TTX-R Iₙₐ）增强[5]。DAMGO（1μM和10μM）预处理TF-1人骨髓祖细胞24小时，DAMGO可降低细胞表面CXCR4受体的表达水平，并显著抑制X4嗜性HIV-1病毒株IIIB在细胞中的的复制[6]。
在体内，DAMGO（10ng）通过立体定向注射至幼年雄性小鼠前扣带皮层（在出生后第6、8和10天给药），DAMGO能够诱导小鼠出现自闭样行为，包括社交互动缺陷、焦虑样行为和刻板行为，并下调前扣带皮层中Grin2b的表达和GluN2B蛋白水平[7]。DAMGO（5–15μg）通过局部（手术部位）或腰椎（L3–L5）鞘内注射至成年（3–6月龄）和老年（24月龄）小鼠（在术后第1天或第1–3天给药）。DAMGO能够剂量依赖性地减轻切口模型诱导的热和机械性术后痛觉过敏。鞘内注射DAMGO（5μg）或系统腹腔注射（1mg/kg）对切口诱导的自发性疼痛的抑制作用在成年小鼠中更为显著[8]。