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阿片肽:一种内源性的人类肽,在多种病理情况下具有有趣的应用。

Opiorphin: an endogenous human peptide with intriguing application in diverse range of pathologies.

机构信息

Chikara College of Pharmacy, Chitkara University, Rajpura, Punjab, 140401, India.

Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, NSW, 2007, Australia.

出版信息

Inflammopharmacology. 2024 Oct;32(5):3037-3056. doi: 10.1007/s10787-024-01526-8. Epub 2024 Aug 20.

Abstract

Mammalian zinc ectopeptidases have significant functions in deactivating neurological and hormonal peptide signals on the cell surface. The identification of Opiorphin, a physiological inhibitor of zinc ectopeptidases that inactivate enkephalin, has revealed its strong analgesic effects in both chemical and mechanical pain models. Opiorphin achieves this by increasing the transmission of endogenous opioids, which are dependent on the body's own opioid system. The function of opiorphin is closely linked to the rat sialorphin peptide, which inhibits pain perception by enhancing the activity of naturally occurring enkephalinergic pathways that depend on μ- and δ-opioid receptors. Opiorphin is highly intriguing in terms of its physiological implications within the endogenous opioidergic pathways, particularly in its ability to regulate mood-related states and pain perception. Opiorphin can induce antidepressant-like effects by influencing the levels of naturally occurring enkephalin, which are released in response to specific physical and/or psychological stimuli. This effect is achieved through the modulation of delta-opioid receptor-dependent pathways. Furthermore, research has demonstrated that opiorphin's impact on the cardiovascular system is facilitated by the renin-angiotensin system (RAS), sympathetic ganglia, and adrenal medulla, rather than the opioid system. Hence, opiorphin shows great potential as a solitary candidate for the treatment of several illnesses such as neurodegeneration, pain, and mood disorders.

摘要

哺乳动物锌外肽酶在细胞表面失活神经和激素肽信号方面具有重要功能。发现阿片啡肽(opiorphin)是锌外肽酶的一种生理性抑制剂,能使内啡肽失活,这揭示了它在化学和机械性疼痛模型中具有很强的镇痛作用。阿片啡肽通过增加内源性阿片类物质的传递来实现这一点,内源性阿片类物质依赖于身体自身的阿片系统。阿片啡肽的功能与大鼠涎液素肽密切相关,涎液素肽通过增强依赖 μ 和 δ 阿片受体的天然内啡肽能通路的活性来抑制疼痛感知。阿片啡肽在内源性阿片能途径中的生理意义非常有趣,特别是在调节与情绪相关的状态和疼痛感知方面。阿片啡肽可以通过影响内源性脑啡肽的水平来诱导抗抑郁样作用,内源性脑啡肽是对特定的身体和/或心理刺激释放的。这种作用是通过调节 δ-阿片受体依赖途径来实现的。此外,研究表明,阿片啡肽对心血管系统的影响是由肾素-血管紧张素系统(RAS)、交感神经节和肾上腺髓质介导的,而不是由阿片系统介导的。因此,阿片啡肽作为治疗神经退行性疾病、疼痛和情绪障碍等多种疾病的单一候选药物具有很大的潜力。

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