Noguchi N, Takasawa S, Nata K, Tohgo A, Kato I, Ikehata F, Yonekura H, Okamoto H
Department of Biochemistry, Tohoku University School of Medicine, Sendai 980-77, Miyagi, Japan.
J Biol Chem. 1997 Feb 7;272(6):3133-6. doi: 10.1074/jbc.272.6.3133.
Cyclic ADP-ribose (cADPR) is a second messenger for Ca2+ mobilization via the ryanodine receptor (RyR) from islet microsomes for insulin secretion (Takasawa, S., Nata, K., Yonekura, H., and Okamoto, H. (1993) Science 259, 370-373). In the present study, FK506, an immunosuppressant that prolongs allograft survival, as well as cADPR were found to induce the release of Ca2+ from islet microsomes. After islet microsomes were treated with FK506, the Ca2+ release by cADPR from microsomes was reduced. cADPR as well as FK506 bound to FK506-binding protein 12.6 (FKBP12.6), which we also found occurs naturally in islet microsomes. When islet microsomes were treated with cADPR, FKBP12.6 dissociated from the microsomes and moved to the supernatant, releasing Ca2+ from the intracellular stores. The microsomes that were then devoid of FKBP12.6 did not show Ca2+ release by cADPR. These results strongly suggest that cADPR may be the ligand for FKBP12.6 in islet RyR and that the binding of cADPR to FKBP12.6 frees the RyR from FKBP12.6, causing it to release Ca2+.
环磷酸腺苷核糖（cADPR）是一种第二信使，可通过胰岛微粒体中的兰尼碱受体（RyR）动员Ca2+以促进胰岛素分泌（高泽，S.，奈田，K.，米仓，H.，和冈本，H.（1993年）《科学》259，370 - 373）。在本研究中，发现延长同种异体移植存活时间的免疫抑制剂FK506以及cADPR均可诱导胰岛微粒体释放Ca2+。用FK506处理胰岛微粒体后，cADPR引起的微粒体Ca2+释放减少。cADPR以及FK506均与FK506结合蛋白12.6（FKBP12.6）结合，我们还发现其天然存在于胰岛微粒体中。用cADPR处理胰岛微粒体时，FKBP12.6从微粒体解离并转移至上清液，从而从细胞内储存库释放Ca2+。随后不含FKBP12.6的微粒体未显示出cADPR引起的Ca2+释放。这些结果有力地表明，cADPR可能是胰岛RyR中FKBP12.6的配体，并且cADPR与FKBP12.6的结合使RyR从FKBP12.6中释放出来，导致其释放Ca2+。
