Modulation of Ca2+ influx by corticotropin-releasing factor (CRF) family of peptides via CRF receptors in rat pancreatic β-cells
Modulation of Ca2+ influx by corticotropin-releasing factor (CRF) family of peptides via CRF receptors in rat pancreatic β-cells
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DOI：
10.1016/j.peptides.2006.01.011
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发表时间：
2006-07-01
期刊：
影响因子：
3
通讯作者：
Wakui, M
中科院分区：
文献类型：
--
作者：
Kageyama, K;Kimura, R;Wakui, M
促肾上腺皮质激素释放因子（CRF）家族肽的作用是由7个跨膜结构域g蛋白偶联受体介导的，即CRF受体1型（CRF2受体）和2型（CRF2受体）。在之前的一项研究中，我们报道了CRF，一种CRF1受体的内源性配体，调节大鼠胰腺β细胞中的Ca2+内流。除了CRF，在哺乳动物中还发现了该家族的其他成员——尿皮质素。Urocortin 1 （UCN 1）是CRF家族的一种肽，可结合CRF1受体和CRF2受体，具有相同的亲和力。尿皮质素3 （ucn3）是一种高选择性的CRF2受体配体，与CRF1受体亲和力低，已在大鼠胰腺β细胞中被发现。本研究的重点是CRF家族肽通过CRF受体对大鼠胰腺β细胞内Ca2+ ([Ca2+](i))浓度的影响。微荧光实验表明，CRF （0.2 nM）和ucn1 （0.2 nM）使[Ca2+]水平升高。应激素（一种非选择性的CRF受体拮抗剂）减弱了CRF和UCN 1的作用。Antisauvagine-30是一种选择性CRF2受体拮抗剂，似乎可以增强UCN 1对[Ca2+]升高的影响(i)。CRF对[Ca2+](i)升高的影响被ucn3的加入所抑制。综上所述，CRF2受体的激活可拮抗CRF1受体刺激的Ca2+内流。(c) 2006爱思唯尔公司版权所有。
The actions of the corticotropin-releasing factor (CRF) family of peptides are mediated by the seven transmembrane-domain G-protein-coupled receptors, the CRF receptors type 1 (CRF2 receptor) and type 2 (CRF2 receptor). In a previous study, we reported that CRF, an endogenous ligand for CRF1 receptor, modulated Ca2+ influx in rat pancreatic beta-cells. In addition to CRF, other additional members of the family, urocortins, have been identified in mammals. Urocortin 1 (UCN 1), a peptide of the CRF family, binds both CRF1 receptor and CRF2 receptor with equal affinities. Urocortin 3 (UCN 3), a highly selective ligand for CRF2 receptor with little affinity for CRF1 receptor, has been shown in rat pancreatic beta-cells. The present study focused on the effects of the CRF family peptides on intracellular Ca2+ ([Ca2+](i)) concentration via CRF receptors in rat pancreatic beta-cells. Microfluorimetric experiments showed that CRF (0.2 nM) and UCN 1 (0.2 nM) elevated [Ca2+], levels. Both CRF and UCN 1 effects were attenuated by astressin, a non-selective CRF receptor antagonist. Antisauvagine-30, a selective CRF2 receptor antagonist, appeared to enhance the UCN 1 effect on the elevation of [Ca2+](i). The CRF effect on the elevation of [Ca2+](i) was inhibited by the addition of UCN 3. Taken together, the activation of CRF2 receptor antagonizes the CRF1 receptor-stimulated Ca2+ influx. (c) 2006 Elsevier Inc. All rights reserved.