Luo Jiangnan, Lushchak Oleh V, Goergen Philip, Williams Michael J, Nässel Dick R
Department of Zoology, Stockholm University, Stockholm, Sweden.
Department of Neuroscience, Uppsala University, Uppsala, Sweden.
PLoS One. 2014 Jun 12;9(6):e99732. doi: 10.1371/journal.pone.0099732. eCollection 2014.
A set of 14 insulin-producing cells (IPCs) in the Drosophila brain produces three insulin-like peptides (DILP2, 3 and 5). Activity in IPCs and release of DILPs is nutrient dependent and controlled by multiple factors such as fat body-derived proteins, neurotransmitters, and neuropeptides. Two monoamine receptors, the octopamine receptor OAMB and the serotonin receptor 5-HT1A, are expressed by the IPCs. These receptors may act antagonistically on adenylate cyclase. Here we investigate the action of the two receptors on activity in and output from the IPCs. Knockdown of OAMB by targeted RNAi led to elevated Dilp3 transcript levels in the brain, whereas 5-HT1A knockdown resulted in increases of Dilp2 and 5. OAMB-RNAi in IPCs leads to extended survival of starved flies and increased food intake, whereas 5-HT1A-RNAi produces the opposite phenotypes. However, knockdown of either OAMB or 5-HT1A in IPCs both lead to increased resistance to oxidative stress. In assays of carbohydrate levels we found that 5-HT1A knockdown in IPCs resulted in elevated hemolymph glucose, body glycogen and body trehalose levels, while no effects were seen after OAMB knockdown. We also found that manipulations of the two receptors in IPCs affected male aggressive behavior in different ways and 5-HT1A-RNAi reduced courtship latency. Our observations suggest that activation of 5-HT1A and OAMB signaling in IPCs generates differential effects on Dilp transcription, fly physiology, metabolism and social interactions. However the findings do not support an antagonistic action of the two monoamines and their receptors in this particular system.
果蝇大脑中的一组14个胰岛素生成细胞（IPC）可产生三种胰岛素样肽（DILP2、3和5）。IPC的活性以及DILP的释放取决于营养物质，并受多种因素控制，如脂肪体衍生蛋白、神经递质和神经肽。IPC表达两种单胺受体，即章鱼胺受体OAMB和5-羟色胺受体5-HT1A。这些受体可能对腺苷酸环化酶起拮抗作用。在此，我们研究这两种受体对IPC活性和输出的作用。通过靶向RNA干扰敲低OAMB会导致大脑中Dilp3转录水平升高，而敲低5-HT1A则会导致Dilp2和Dilp5增加。在IPC中进行OAMB-RNA干扰会使饥饿果蝇的存活时间延长且食物摄入量增加，而5-HT1A-RNA干扰则产生相反的表型。然而，在IPC中敲低OAMB或5-HT1A均会导致对氧化应激的抗性增加。在碳水化合物水平测定中，我们发现敲低IPC中的5-HT1A会导致血淋巴葡萄糖、身体糖原和海藻糖水平升高，而敲低OAMB后则未观察到影响。我们还发现，对IPC中这两种受体的操作对雄性攻击行为有不同影响，且5-HT1A-RNA干扰会缩短求偶潜伏期。我们的观察结果表明，IPC中5-HT1A和OAMB信号的激活对Dilp转录、果蝇生理、代谢和社会互动产生不同影响。然而，这些发现并不支持这两种单胺及其受体在该特定系统中的拮抗作用。
