| Co-Investigator(Kenkyū-buntansha) |
TINDARO Rend ローマ大学, 医学部(イタリア共和国), 教授
MAEDA Toshihiro Shiga University of Medical Science Department of Anatomy, Professor, 医学部, 教授 (50028388)
TOOYAMA Ikuo Shiga University of Medical Science, Molecular Neurobiology Research Center, Ass, 分子生物学研究センター, 助教授 (20207533)
RENDA Tindaro University of Rome Institute of Human Anatomy, Professor
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| Research Abstract |
[D-Ala2] Deltorphin I (Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2 : DADTI), an opioid peptide recently isolated from the skin of the south African frog Phyllomedusa bicolor, displays high affinity and selectivity for delta-opioid receptors. cDNAs encoding deltorphin precursors have been cloned from the skin of the same amphibian species. The precursors contain three DADTI sequences and only a single [D-Ala2] deltorphin II sequence. Because its L-isomer is pharmacologically inactive, D-alanine or at least D-amino acid in the second position appears essential to its opiate-like activity. In other words, the carboxy-terminal region of deltorphines seems crucial for addressing the molecules towards the delta-type receptor. More recently, Professor Tindaro Renda and Assistant Professor Ikuo Tooyama, both are the members of this joint project, have demonstrated that DADTI-binding sites by radioautography in brains of the rat and mouse. When injeced into the rat cerebral ventricle, DADTI induces sever
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al central effects including stimulation of locomotor activity, sniffing, rearing, grroming, as well as facillitation of social contacts and memory consolidation.
In addition to the findings described above, we have succeeded in the production of both polyclonal and monoclonal antibodies that specifically recognizes its carboxy-terminal tetrapeptide region. Immunohistochemical studies of mouse ad rat brains have detected DADTI-immunoreactive neuronal cell bodies and their processes in certain brain regions. These positive structures in the brain have been mapped in both adult and infant animals. We have also published a paper concerning DADTI-positive neurons in the substantia nigra, in relation with the coexistence of dopamine and calbindin-28K.The results were discussed with possible physiological function of DADTI in the brain. Finally, our study using molecular biology is progressing to identify the existence of mRNA encoding DADTI-like molecule in the mammalian brain, and the results will be published after the precise determination of the amino acid sequence. It is therefore concluded that the joint study supported by this grant has been sucessful, and a further study is promising on this novel peptide as an bioctive neuropeptide in mammals. Less
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