Recent Advances in the Search for the μ-Opioidergic System : Isolation and Distribution of Endomorphins in the Central Nervous System

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概要

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• Endomorphin-1 (Tyr-Pro-Trp-Phe-NH2, EM-1) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH2, EM-2) have the highest affinity and selectivity for the μ-opioid receptor (MOP-R) of all known mammalian opioids. They were isolated from bovine and human brain, and are structurally distinct from the other endogenous opioids. Both EM-1 and EM-2 have potent antinociceptive activity in a variety of animal models of acute, neuropathic and allodynic pain. They regulate cellular signaling processes in a manner consistent with MOP-R-mediated effects. The EMs are implicated in the natural modulation of pain by extensive data localizing EM-like immunoreactivity (EM-LI) near MOP-Rs in several regions of the nervous system known to regulate pain. These include the primary afferents and their terminals in the spinal cord dorsal horn, where EM-2 is well-positioned to modulate pain in its earliest stages of perception. In a nerve-injury model of chronic pain, a loss of spinal EM2-LI occurs concomitant with the onset of chronic pain. The distribution of the EMs in other areas of the nervous system is consistent with a role in the modulation of diverse functions, including autonomic, neuroendocrine and reward functions as well as modulation of responses to pain and stress. Unlike several other μ opioids, the threshold dose of EM-1 for analgesia is well below that for respiratory depression. In addition, rewarding effects of EM-1 can be separated from analgesic effects. These results indicate a favorable therapeutic profile of EM-1 relative to other μ opioids. Thus, the pharmacology and distribution of EMs provide new avenues both for therapeutic development and for understanding the neurobiology of opioids.

• 社団法人 日本薬理学会の論文
• 2002-07-01

著者

• ZADINA James

  Department of Veterans Affairs Medical Center

• Zadina J

  Department Of Medicine And Neuroscience Program Tulane University School Of Medicine And Department

関連論文

• Recent Advances in the Search for the μ-Opioidergic System : Morphological Studies of the Endomorphinergic Neurons in the Central Nervous System
• Recent Advances in the Search for the μ-Opioidergic System : Isolation and Distribution of Endomorphins in the Central Nervous System

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