| Co-Investigator(Kenkyū-buntansha) |
YAMAMURA Yoshitaka Otsuka Phramaceuti. Co. LTD,Researcher, 研究所, 研究員
YAMADA Katsushi Kogoshima Univ., Fac. Medicine, Prof., 医学部, 教授 (00037491)
HONDA Kenji Fukuoka Univ., Faculty of Pharmaceutical Sciences, Assist Prof., 薬学部, 助手 (60140761)
FUJIWARA Michihiro Fukuoka Univ., Faculty of Pharmaceutical Sciences, Prof., 薬学部, 教授 (10091331)
TAKANO Yukio Fukuoka Univ., Faculty of Pharmaceutical Sciences, Asso. Prof., 薬学部, 助教授 (50113246)
SHIMOHIGASHI Yasuyuki Kyushu Univ.Faculty of Sciences, Asso. Prof., 理学部, 助教授 (00211293)
SAITO Ryo Fukuoka Univ., Faculty of Pharmaceutical Sciences, Assist Prof., 薬学部, 助手 (80122696)
|
|---|
| Research Abstract |
1. Phamacological properties of AVP receptor subtype participating in brain function
(1) Specific _3H-AVP binding sites to the V1 receptor were observed in the septum, hippocampus and several areas of hind brain using a binding assay and a quantitative autoradiography.
(2) The subtypes of AVP receptor in some areas observed in this study were as follows : (1) The sensitivity of baroreceptor reflex in nomotensive rats was inhibited by the V1 receptor in the area postrema (AP), while an increase in the sensitivity of the baroreceptor reflex in the initial stage of a one-kidney one clip (1K 1C) hypertensive rats was reversed by microinjection of V1 or V2 antagonists into the AP.(2) RT-PCR assay was carried out for measurement of AVP receptor mRNA from 1K 1C rat brain. V2 receptor PCR products were detected in the initial stage of 1K 1C rats in the AP and nucleus tractus solitarius. These results suggest that AVP receptor subtypes in the AP play very important roles in development of some kind of hypertension. (3) V1 receptor was involved in the impairment of spatial cognition with an AVP metabolize, AVP 4-9.
2. Studies based on peptide chemistry and medicinal chemistry
In order to obtain high selective ligands for AVP receptor subtype related to cognitive enhancement, a series of AVP analogues was designed and synthesized. Many fundamental problems on peptide constitution-actiuity relationship still remain to he resolved.
|
