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  • A previous study suggested that DARs and octopamine tyramine

    2019-08-21

    A previous study suggested that DARs and octopamine/tyramine receptors (OARs/TARs) have close pharmacological properties (Beggs et al., 2011). Their relationships were also supported by phylogenetic analyses (Balfanz et al., 2005, Hauser et al., 2008, Wu et al., 2014), indicating that some of DAR and OAR genes are paralogues. The most recent classification system for insect octopamine receptors into α-adrenergic-like octopamine receptors (α1 as OA1, α2 as OA3), β-adrenergic-like octopamine receptors (OA2), and octopamine/tyramine or tyramine receptors (TA1, TA2, and TA3), was based on their similarities in structural and signaling properties (Bayliss et al., 2013, Evans and Maqueira, 2005, Huang et al., 2007, Huang et al., 2009, Wu et al., 2014, Wu et al., 2015b). DOP1 is pharmacologically most similar to OA2, and activation of DOP1 increases intracellular cyclic adenosine monophosphate (cAMP) levels (Chen et al., 2010, Meyer et al., 2011, Mitsumasu et al., 2008, Mustard et al., 2003). DOP2 shares similar pharmacological properties with OA1, and activation of DOP2 has been shown to increase both intracellular cAMP and calcium levels (Beggs et al., 2011, Huang et al., 2010, Huang et al., 2012, Troppmann et al., 2014). DOP3 is functionally similar to TA1, and activation of DOP3 decreases intracellular cAMP levels and increases calcium levels (Gross et al., 2015, Verlinden et al., 2015, Wu et al., 2013a). The rice striped stem borer, Chilo suppressalis (Walker) (Lepidoptera: Crambidae) is one of the most economically important rice pests in Asia, northern Africa, and southern Europe (He et al., 2014). It causes serious crop loss every year, particularly in China because of rice cultivation and the popularization of hybrid varieties. To date, chemical control is still the major method to protect rice from damage by the rice stem borer. Unfortunately, C. suppressalis has developed resistance to many chemical insecticides and the estimated cost for controlling this pest is approximately 160,000,000 US dollars annually (Wu et al., 2013b). GPCRs are successful pharmaceutical targets with over one third of human drugs acting on these receptors or their downstream signaling processes (Rask-Andersen et al., 2011). Invertebrate GPCRs have long been suggested as targets for the development of new c di gmp to of insecticides (Audsley and Down, 2015). Several studies suggested that interference with DA signaling may cause insect death or result in a variety of phenotypes such as incapacitation and disrupted development that are highly attractive for insecticide development (Bai et al., 2011, Conley et al., 2015, Fuchs et al., 2014, Hill et al., 2013, Nuss et al., 2015). In this study, we comprehensively analyzed pharmacological properties of CsDOP1, CsDOP2 and CsDOP3 from C. suppressalis, in a heterologous expression system.
    Materials and methods
    Results and discussion
    Acknowledgements This work was supported by the National Natural Science Foundation of China (31572039), the National Program on Key Basic Research Projects (973 Program, 2013CB127600) and China Postdoctoral Science Foundation (2016M601946).
    Introduction Parkinson\'s disease (PD) is a neurological disorder afflicting 10 million people worldwide (Wirdefeldt et al., 2011). In an estimated 90% of PD patients the cause of the disease is unknown, having no clear genetic or environmental origin (de Lau and Breteler, 2006). The most pronounced neuropathological feature of PD is the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta and the consequent reduction in dopamine levels in the striatum, which manifest as impairments in motor function (e.g., rigidity, tremor, bradykinesia) (Samii et al., 2004). Notably, this degeneration appears to be preceded by the loss of the dopaminergic phenotype; that is, at least some dopaminergic neurons first stop producing and signaling with dopamine prior to degenerating (Janezic et al., 2013). Although the molecular basis for idiopathic PD remains incompletely understood, it has been proposed to include oxidative stress, mitochondrial dysfunction, and dysregulation of dopamine homeostasis (Blesa et al., 2015, Hauser and Hastings, 2013, Hwang, 2013). Currently there are no available treatments that stop or even slow the progression of PD. Existing therapeutics relieve PD symptoms by increasing dopaminergic signaling through one of three mechanisms: (1) increasing dopamine levels by augmenting the amount of its biosynthetic precursor, L-DOPA; (2) blocking the breakdown of dopamine by inhibiting its metabolic enzymes (MAO, COMT); and (3) mimicking the activity of dopamine by directly agonizing dopamine receptors. However, these drugs only partially alleviate symptoms and can have significant side effects, especially as the disease progresses. New types of therapeutics are desperately needed to combat both the symptoms and progression of PD.