Azusa Sugimoto-Watanabe, Kazufumi Kubota, Kenji Fujibayashi and Koji
Neuroscience and Immunology Research Laboratories, Sankyo Co., Ltd., 2 - 58, Hiromachi 1-chome, Shinagawa-ku, Tokyo 140 - 8710, Japan
Abstract: Recently discovered endomorphin-1 and -2 are the first endogenous agonists selective for the É -opioid receptor. We examined the antinociceptive effect and enzymatic degradation of endomorphin-1 in the newborn rat spinal cord. Endomorphin-1 inhibited the binding of [3H][d-Ala2, N-Me-Phe4, Gly-ol5] enkephalin (DAMGO) to the membrane fraction of the newborn rat spinal cord as potently as DAMGO and morphine. Endomorphin-1 at 1 - 1,000 nM reduced the slow ventral root potential, which reflects noxious transmission in the isolated newborn rat spinal cord, concentration-dependently via the É -opioid receptor. A similar effect was observed with endomorphin-2. The newborn rat spinal cord homogenate degraded endomorphin-1 in a 120-min incubation procedure, while it degraded [Leu5]enkephalin even in a 30-min incubation procedure. The degradation of endomorphin-1 was inhibited by actinonin but not by thiorphan. These results showed that in the newborn rat spinal cord, endomorphins had high affinity for the É -opioid receptor and exerted É -opioid-receptor-mediated inhibitory effects on noxious responses. Endomorphin-1 was degraded by peptidases, but slowly compared with [Leu5]enkephalin degradation, and the degrading enzymes were actinonin-sensitive peptidases.
Keywords: Endomorphin-1 and -2, Enkephalin, Spinal cord, Slow ventral root potential, Enzymatic degradation