Gromada J, Rorsman P, Dissing S, Wulff B S
Novo Nordisk A/S, Copenhagen, Denmark.
FEBS Lett. 1995 Oct 9;373(2):182-6. doi: 10.1016/0014-5793(95)01070-u.
The actions of glucagon-like peptide-1(7-36)amide (GLP-1(7-36)amide) on cellular signalling were studied in human embryonal kidney 293 (HEK 293) cells stably transfected with the cloned human GLP-1 receptor. The cloned GLP-1 receptor showed a single high-affinity binding site (Kd = 0.76 nM). Binding of GLP-1(7-36)amide stimulated cAMP production in a dose-dependent manner (EC50 = 0.015 nM) and caused an increase in the intracellular free Ca2+ concentration ([Ca2+]i). The latter effect reflected Ca(2+)-induced Ca2+ release and was suppressed by ryanodine. We propose that the ability of GLP-1(7-36)amide to increase [Ca2+]i results from sensitization of the ryanodine receptors by a protein kinase A dependent mechanism.
在稳定转染了克隆的人胰高血糖素样肽-1受体的人胚肾293（HEK 293）细胞中，研究了胰高血糖素样肽-1(7 - 36)酰胺（GLP-1(7 - 36)酰胺）对细胞信号传导的作用。克隆的GLP-1受体显示出单一的高亲和力结合位点（解离常数Kd = 0.76 nM）。GLP-1(7 - 36)酰胺的结合以剂量依赖方式刺激环磷酸腺苷（cAMP）的产生（半数有效浓度EC50 = 0.015 nM），并导致细胞内游离钙离子浓度（[Ca2+]i）升高。后一种效应反映了钙诱导的钙释放，并且被ryanodine（一种药物）所抑制。我们提出，GLP-1(7 - 36)酰胺增加[Ca2+]i的能力是由蛋白激酶A依赖性机制使ryanodine受体致敏所致。
