Antinociceptive effect and enzymatic degradation
of endomorphin-1 in newborn rat spinal cord

Sugimoto-Watanabe A, Kubota K, Fujibayashi K, Saito K
Neuroscience and Immunology Research Laboratories,
Sankyo Co., Ltd., Tokyo, Japan.
Jpn J Pharmacol 1999 Nov; 81(3):264-70


Recently discovered endomorphin-1 and -2 are the first endogenous agonists selective for the mu-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 mu-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 mu-opioid receptor and exerted mu-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.
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