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2000年 神経化学会英文抄録

Metabotropic neurosteroid/sigma receptors are sensitive to some endocrine disruptors

Hiroshi Ueda, Yoshida Akira

Neurosteroids which are steroid hormones generated in nervous system affect on neuronal functions. They are involved in neuronal development and psychopharmacological actions. In general, steroid hormones act on their intranuclear receptor and regulate transcriptional activities. However, the different types of receptors for neurosteroids have been suggested to exist on cell surface membrane, and to share some pharmacological properties with six receptors. Previously, a novel sigma-ligand receptor is a possible candidate for the neurosteroid receptor. Previously, we have reported the presence of metabotropic sigma receptor in experiments measuring agonist-stimulated G protein activity of synaptic membranes. Here we observed that dehydroepiandrosterone sulfate (DHEAS, a neurosteroid) also stimulated G protein activity derived from Gi1 in reconstitution experiments, and they were blocked by progesterone (PROG), another neurosteroid and NE-100, a sigma receptor antagonist. On the other hand, the pentazocine, a sigma receptor agonist stimulated G protein activity in a reversible manner with PROG and NE-100. In the peripheral flexor test in mice, on the other hand, intraplantar injection of sigma agonists and neurosteroids showed Gi1-mediated nociceptive responses through such common receptor mechanisms on nociceptor endings of polymodal C-fibers. The DHEAS-induced nociceptive responses were partially inhibited by endocrine disruptors, such as 1,3-diphenylpropane, methoxychlor, and 4,4ユ-DDE, a metabolite of DDT.