Azusa Sugimoto-Watanabe, Kazufumi Kubota, Kenji Fujibayashi and Koji
Saito
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 μ-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 μ-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 μ-opioid
receptor and exerted μ-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