Differential signaling signatures evoked by DOI versus lisuride stimulation of the 5-HT2A receptor
Differential signaling signatures evoked by DOI versus lisuride stimulation of the 5-HT2A receptor
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DOI：
10.1016/j.bbrc.2020.08.022
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发表时间：
2020-10-22
影响因子：
3.1
通讯作者：
Vaidya, Vidita A.
中科院分区：
文献类型：
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作者：
Banerjee, Antara A.;Vaidya, Vidita A.
5-HT2A受体是致幻和非致幻配体的靶标，可引起独特的行为、电生理和分子后果。在这里，我们探讨了不同的5-HT2A受体配体对5-HT2A受体下游信号通路的差异作用。致幻性5-HT2A受体激动剂DOI与非致幻性5-HT2A受体激动剂lisuride相比，在表达HEK293细胞系和皮质神经元培养物中表达5-HT2AR-EGFP受体的人/大鼠中引起了更强的信号反应。我们注意到，在DOI刺激5-HT2A受体后，磷酸化- plc、pPKC、pERK、pCaMKII、pCREB的水平更高，IP3和DAG的产生水平也更高。我们的研究揭示了不同的信号信号特征，不同的幅度和动力学在5-HT2A受体响应DOI与lisuride。(C) 2020爱思唯尔公司版权所有。
The 5-HT2A receptor is a target for hallucinogenic and non-hallucinogenic ligands that evoke unique behavioral, electrophysiological and molecular consequences. Here, we explored the differential effects of distinct 5-HT2A receptor ligands on signaling pathways downstream to the 5-HT2A receptor. The hallucinogenic 5-HT2A receptor agonist DOI evoked an enhanced signaling response compared to the non-hallucinogenic 5-HT2A receptor agonist lisuride in human/rat 5-HT2AR-EGFP receptor expressing HEK293 cell lines and cortical neuronal cultures. We noted higher levels of phospho-PLC, pPKC, pERK, pCaMKII, pCREB, as well as higher levels of IP3 and DAG production following 5-HT2A receptor stimulation with DOI. Our study reveals distinct signaling signatures, differing in magnitude and kinetics at the 5-HT2A receptor in response to DOI versus lisuride. (C) 2020 Elsevier Inc. All rights reserved.