| Co-Investigator(Kenkyū-buntansha) |
STEINBUSCH Harry Maaslicht University School of Medicine, 医学部, 教授
TIMMERMAN Hendrik Free University Amsterdam School of Science, 理学部, 教授
HORIO Yoshiyuki Osaka University Faculty of Medicine, 医学部, 講師 (30181530)
YANAI Kazuhiko Tohoku University School of Medicine, 医学部, 講師 (50192787)
YAMATODANI Atsushi Osaka University Faculty of Medicine, 医学部, 教授 (30116123)
FUKUI Hiroyuki Osaka University Faculty of Medicine, 医学部, 助教授 (90112052)
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| Research Abstract |
1. The genes of histamine H1 receptors of rats, guinea-pigs and humnans were cloned : The numbers of amino acids of the respective H1 receptors were 486,488 and 487. The mechanism of the up-regulation of human H1 receptors by phorbol ester was studied. Site directed mutagenesis showed that Asp107, Asn198 and Tyr431 are important in the binding of histamine to H1 receptors. Quinine, a ligand for cytochrome P450-IID,was not bound to expressed H1 receptors, but central and peripheral tissues had quinine sensitive sites to which H1 antagonists were also bound.
2. The positron emission tomography (PET) of H1 receptors in human brains showed that the density is increased around the epileptic foci in brains of patients with partial complex seizure. H1 receptors decreased in brains of patients of Alzheimer's disease and multi-infarct dementia when compared with those of sex-and age-matched normal volunteers.
3. A trihydroxyhistidine analog, a possible histamiergic specific neurotoxin, did not destroy the histaminergic neurons in the hypothalamus of rats, but ibotenate, a specific NMDA-1 antagonist, destroyed the neurons.
4. The effects of immepip, a new H3 agonist and clobenpropit, a new H3 antagonist on the releases of histamine and GABA were studied by microdialysis technique in rat brains. Immepip inhibited histamine release, but did not affect GABA release. Clobenpropit enhanced histamine release, but did not affect GABA release. On the other hand, thioperamide, an original H3 antagonist, increased the releases of both histamine and GABA.Clobenpropit shortened the duration of electroconvulsion in mice in a greater degree than thioperamide.
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