title: Antinociceptive effect and enzymatic degradation of endomorphin-1 in newborn rat spinal cord.
abstract: 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.
authors.affiliation: Neuroscience and Immunology Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Sugimoto-Watanabe
authors.forename: K
authors.initials: K
authors.lastname: Kubota
authors.forename: K
authors.initials: K
authors.lastname: Fujibayashi
authors.forename: K
authors.initials: K
authors.lastname: Saito
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001667:Binding, Competitive; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000378:metabolism; D004743:Enkephalin, Leucine / Q000378:metabolism; D005260:Female; D006868:Hydrolysis; D008564:Membrane Potentials / Q000187:drug effects; D009842:Oligopeptides / Q000378:metabolism / Q000494:pharmacology*; D011247:Pregnancy; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism
chemical_list: D009842:Oligopeptides; D011480:Protease Inhibitors; C105293:endomorphin 1; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004743:Enkephalin, Leucine