| 特集名 | 消化管機能と受容体 -- 臨床とのかかわり | |
|---|---|---|
| 題名 | コレシストキニン(CCK)受容体 | |
| 発刊年月 | 2000年 04月 | |
| 著者 | 船越 顕博 | 国立病院九州がんセンター消化器部 |
| 【 要旨 】 | CCK受容体にはCCK-A,-B受容体の2種が存在し,それぞれ別個の遺伝子に由来し,膜7回貫通型のG蛋白共役型である.本稿ではCCK-A受容体の構造,機能,さらに最近明らかになった疾病との関わりについて概説した.また,自然発症CCKA受容体ノックアウトラットの発見から,従来の拮抗剤を用いる薬理学的実験に比べ,CCK-A受容体の生理機能解析が進歩した.CCK-A受容体は胆嚢収縮,膵外分泌刺激に関与するとされていたが,ヒト膵臓ではCCK-B受容体が主であり,膵外分泌機能とCCK-A受容体との関係は間接作用が示唆される.臨床的にはCCK-A受容体機能異常,および遺伝子異常と疾病の関係は胆石症,肥満で興味あるデータが集積されつつある. | |
| Theme | The Role of Receptors in Gastrointestinal Functions | |
|---|---|---|
| Title | Cholecystokinin(CCK) Receptors | |
| Author | Akihiro Funakoshi | Department of Gastroenterology, National Kyushu Cancer Center |
| [ Summary ] | Two types of cholecystokinin(CCK) receptors(type A and type B), which are seven transmembrane G-protein coupled receptors, have been identified on the basis of their affinities for a structurally and functionally related family of peptides, with identical COOH-terminal pentapeptide sequences. These receptors were cloned, and a CCK-B receptor(CCK-BR) gene was found to be identical to the gastrin receptor gene. We demonstrated the absence of the CCK-AR gene expression due to a genetic abnormality in OLETF rats, which show a tendency toward obesity and non-insulin dependent diabetes mellitus, although the expression of the CCK-BR gene was intact. This rat is a naturally occurring CCK-AR knockout rat, and a useful tool for evaluating CCK-AR functions. CCK stimulates pancreatic enzyme secretion and produces gall-bladder contraction, through CCK-AR. In the human pancreas CCK-BR mRNA was expressed, but not CCK-AR, indicating an indirect effect on exocrine pancreatic functioning. The polymorphism in the promoter region of the CCK-AR gene may be a genetic factor, affecting obesity and abnormalities in gallbladder contraction. | |