Screening Of Chemical Compounds For Sleep Disorders By Three Types Of G-protein-coulpled Receptor Sensor

Insomnia(insomnia)is a common sleep disorders,the prevalence of the crowd is extremely high,not only affect people’s quality of life,but also with depression,anxiety and other diseases are closely related.Further triggering a variety of metabolic diseases,such as:type 2 diabetes.Human sleep is regulated by a series of receptors,which include:GABAA receptors,Melatonin receptors,Serotonin receptors,Orexin receptors,Histamine receptors,Adenosine receptors and dopa dopamine receptors.In addition to GABAA receptors,the rest of the receptors belong to the G protein-coupled receptor.Commercially available treatment of insomnia drugs mainly for the GABAA receptor to play a role,because the GABAA receptor in the nervous system diffuse distribution,so these drugs diffuse inhibition of the central nervous system and block the brain stem network structure of the activation system Conduction function,so that the cerebral cortex cells from excitement to inhibition.However,some of these drugs can cause withdrawal syndrome and have adverse effects such as daytime effects.A new drug for the treatment of insomnia such as melatonin(MT1/MT2)receptor agonists,serotonin(5HT2A)receptor modulators and orexin(OXR)receptor antagonists are specific for G protein coupling(GPCR),does not affect the GABAA receptor,in the regulation of sleep behavior side effects less.In this study,using the method of fluorescence resonance energy transfer to construct the molecular probe with GPCR spatial structure and the method of inducing receptor expression,it can identify whether the compound has specific effect on GPCR,so as to screen out the compounds which may have sedative and soothing effects Development.In this study,we used serotonin 5HT2A/1B receptor,dopamine D2/D3 receptor and orexin OX2 receptor to study the G protein-coupled receptor associated with sleep regulation.First,the dopamine D2/D3 receptor expression vector and the 5HT2A/1B receptor probe vector with fluorescent groups were constructed,which was the basis for the construction of stable cell lines.Then,a stable cell line expressing dopamine D2/D3 receptor and serotonin 5HT2A/1B receptor probe was established to construct a drug screening with dopamine D2/D3 receptor and serotonin 5HTZA/1B receptor as a preset target platform.Finally,we used a laboratory-based stable cell line that induced the expression of the orexin OX2 receptor to screen for a range of compounds.The results showed that the drug screening platform with dopamine D2/D3 receptor and serotonin 5HT2A/1B receptor as a preset target was successfully constructed,which provided theoretical support for the development of insomnia drug.In addition,the activity of the compounds was screened using a stable cell line that induced the expression of the orexin OX2 receptor,and a series of appetite peptide receptor antagonists(in collaboration with the Chinese Academy of Sciences Shanghai Pharmaceuticals)were screened for a variety of sedative and sedative effects The active ingredient provides data support for the treatment of insomnia drugs for targeted ovarian receptors.