薬理学の新世紀を拓く　　“Ｔｈｅ　ＣＤ３８‐ｃｙｃｌｉｃ　ＡＤＰ‐ｒｉｂｏｓｅ　ｓｉｇｎａｌ　ｓｙｓｔｅｍ”　その分子機構と医学・生物学上の意義

• 岡本 宏

  東北大学大学院医学系研究科生物化学分野

書誌事項

タイトル別名

• A New Century of Pharmacology Is Coming. "The CD38-cyclic ADP-ribose signal system": Molecular mechanism and biological significance.
• CD38 cyclic ADP-ribose signal system ソノ ブンシ キコウ ト イガク セイブツガク ジョウ ノ イギ
• 薬理学の新世紀を拓く

抄録

Glucose induces an increase in the intracellular Ca²⁺ concentration in pancreatic β-cells to secrete insulin. CD38 exists in β-cells and has both ADP-ribosyl cyclase, which catalyzes the formation of cyclic ADP-ribose (cADPR) from NAD⁺, and cADPR hydrolase, which converts cADPR to ADP-ribose. ATP, produced by glucose metabolism, competes with cADPR for the binding site, Lys-129, of CD38, resulting in the inhibition of the hydrolysis of cADPR and thereby causing cADPR accumulation in β-cells. cADPR then binds to FK506-binding protein 12.6 (FKBP12.6) in the islet type of the ryanodine receptor (RyR), dissociating the binding protein from RyR to induce the release of Ca²⁺ from the endoplasmic reticulum. Ca²⁺/calmodulin-dependent protein kinase II (CaM kinase II) phosphorylates RyR to sensitize and activate the Ca²⁺ channel. Ca²⁺, released from the RyR, further activates CaM kinase II and amplifies this process. Thus, cADPR acts as a second messenger for Ca²⁺ mobilization to secrete insulin. The novel mechanism of insulin secretion described above is different from the conventional hypothesis in which Ca²⁺ influx from extracellular sources plays a role in insulin secretion by glucose. Furthermore, many physiological and pathological phenomena in various tissues and cells such as cardiac muscles, cerebellum, neuronal cells, pancreatic acinar cells, alveolar macrophages and immune B-cells become understandable in terms of “the CD38-cADPR signaling system” that sometimes acts in cooperation with other signal systems.

収録刊行物

• 日本薬理学雑誌

  日本薬理学雑誌 114 (3), 131-139, 1999

  公益社団法人 日本薬理学会

キーワード

• サイクリックADPリボース
• CD38
• インスリン分泌
• 細胞内Ca<SUP>2+</SUP>動員
• リアノジン受容体

詳細情報

• CRID: 1390282679249656704
• NII論文ID: 10005088167
• NII書誌ID: AN00198335
• DOI: 10.1254/fpj.114.131
• COI: 1:CAS:528:DyaK1MXls1Kns74%3D
• ISSN: 13478397
• ISSN: 00155691
• NDL書誌ID: 4819456
• PubMed: 10553576
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I4819456
• Web Site: https://search.jamas.or.jp/link/ui/2000023944
• 本文言語コード: ja
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可