Higashida H, Yokoyama S, Hoshi N, Hashii M, Egorova A, Zhong Z G, Noda M, Shahidullah M, Taketo M, Knijnik R, Kimura Y, Takahashi H, Chen X L, Shin Y, Zhang J S
Department of Biophysical Genetics, Molecular Medicine and Bioinformatics, Kanazawa University Graduate School of Medicine, Japan.
Biol Chem. 2001 Jan;382(1):23-30. doi: 10.1515/BC.2001.004.
Muscarinic acetylcholine receptors in NG108-15 neuroblastoma x glioma cells, and beta-adrenergic or angiotensin II receptors in cortical astrocytes and/or ventricular myocytes, utilize the direct signaling pathway to ADP-ribosyl cyclase within cell membranes to produce cyclic ADP-ribose (cADPR) from beta-NAD+. This signal cascade is analogous to the previously established transduction pathways from bradykinin receptors to phospholipase Cbeta and beta-adrenoceptors to adenylyl cyclase via G proteins. Upon receptor stimulation, the newly-formed cADPR may coordinately function to upregulate the release of Ca2+ from the type II ryanodine receptors as well as to facilitate Ca2+ influx through voltage-dependent Ca2+ channels. cADPR interacts with FK506, an immunosuppressant, at FKBP12.6, FK506-binding-protein, and calcineurin, or ryanodine receptors. cADPR also functions through activating calcineurin released from A-kinase anchoring protein (AKAP79). Thus, some G(q/11)-coupled receptors can control cADPR-dependent modulation in Ca2+ signaling.
NG108 - 15神经母细胞瘤x胶质瘤细胞中的毒蕈碱型乙酰胆碱受体，以及皮质星形胶质细胞和/或心室肌细胞中的β - 肾上腺素能受体或血管紧张素II受体，利用细胞膜内通向ADP - 核糖基环化酶的直接信号通路，从β - NAD +产生环ADP - 核糖（cADPR）。该信号级联类似于先前建立的从缓激肽受体到磷脂酶Cβ以及从β - 肾上腺素能受体到腺苷酸环化酶经G蛋白的转导途径。受体受刺激后，新形成的cADPR可能协同发挥作用，上调II型兰尼碱受体释放Ca2 +，并促进Ca2 +通过电压依赖性Ca2 +通道内流。cADPR在FKBP12.6（FK506结合蛋白）、钙调神经磷酸酶或兰尼碱受体处与免疫抑制剂FK506相互作用。cADPR还通过激活从A激酶锚定蛋白（AKAP79）释放的钙调神经磷酸酶发挥作用。因此，一些G（q/11）偶联受体可以控制Ca2 +信号传导中依赖cADPR的调节。
