Arthropod D2 receptors positively couple with cAMP through the Gi/o protein family
Arthropod D2 receptors positively couple with cAMP through the Gi/o protein family
复制标题
DOI：
10.1016/j.cbpb.2006.08.018
复制
发表时间：
2007-01-01
影响因子：
2.2
通讯作者：
Baro, Deborah J.
中科院分区：
文献类型：
--
作者：
Clark, Merry C.;Baro, Deborah J.
幽门神经网络是理解节律性运动行为（如呼吸或行走）的神经调节的重要模型系统。多巴胺（DA）差异调节幽门网络内的神经元。然而，虽然DA的电生理作用已经得到很好的表征，但对介导其作用的信号事件一无所知。我们已经开始在这个无脊椎动物系统的DA受体（DARs）的分子特征。在这里，我们描述了龙虾D-2受体，D-2 α泛的克隆和表征。我们发现，当在HEK细胞中表达时，D-2 α Pan受体被DA激活，而不是龙虾神经系统内源性的其他单胺。该受体通过多种Gi/o蛋白经由两种离散途径与cAMP正性偶联：1）G α介导的腺苷酸环化酶（AC）抑制，导致cAMP减少，和2）G β γ介导的磷脂酶β（PLC β）活化，导致cAMP增加。选择性剪接改变受体的效力和功效，但不影响单胺特异性。最后，我们表明，节肢动物D-2受体与cAMP偶联随细胞环境而变化。(c)2006年爱思唯尔公司All rights reserved.
The pyloric network is an important model system for understanding neuromodulation of rhythmic motor behaviors like breathing or walking. Dopamine (DA) differentially modulates neurons within the pyloric network. However, while the electrophysiological actions of DA have been well characterized, nothing is known about the signaling events that mediate its effects. We have begun a molecular characterization of DA receptors (DARs) in this invertebrate system. Here, we describe the cloning and characterization of the lobster D-2 receptor, D-2 alpha Pan. We found that when expressed in HEK cells, the D-2 alpha Pan receptor is activated by DA, but not other monoamines endogenous to the lobster nervous system. This receptor positively couples with cAMP through multiple Gi/o proteins via two discrete pathways: 1) a G alpha mediated inhibition of adenylyl cyclase (AC), leading to a decrease in cAMP and 2) a G beta gamma-mediated activation of phospholipase beta (PLC beta), leading to an increase in cAMP. Alternate splicing alters the potency and efficacy of the receptor, but does not affect monoamine specificity. Finally, we show that arthropod D-2 receptor coupling with cAMP varies with the cellular milieu. (c) 2006 Elsevier Inc. All rights reserved.