scholarly journals Role of the G-Protein-Coupled Receptor Signaling Pathway in Insecticide Resistance

2019 ◽  
Vol 20 (17) ◽  
pp. 4300 ◽  
Author(s):  
Ting Li ◽  
Nannan Liu

The G-protein-coupled receptor (GPCR) regulated intracellular signaling pathway is known to be involved in the development of insecticide resistance in the mosquito, Culex quinquefasciatus. To elucidate the specific role of each effector in the GPCR regulating pathway, we initially expressed a GPCR, G-protein alpha subunit (Gαs), adenylate cyclase (AC), and protein kinase A (PKA) in insect Spodoptera frugiperda (Sf9) cells and investigated their regulation function on cyclic AMP (cAMP) production and PKA activity. GPCR, Gαs, and AC individually expressed Sf9 cells showed higher cAMP production as the expression of each effector increased. All the effector-expressed cell lines showed increased PKA activity however. Moreover, Sf9 cytochrome P450 gene expression and cell tolerance to permethrin were examined. The relative expression of CYP9A32gene in Sf9 cells tested was significantly increased in all effector-expressed cell lines compared to a control cell line; these effector-expressed cell lines also showed significantly higher tolerance to permethrin. Inhibitor treatments on each effector-expressed cell line revealed that Bupivacaine HCl and H89 2HCl robustly inhibited cAMP production and PKA activity, respectively, resulting in decreased tolerance to permethrin in all cell lines. The synergistic functions of Bupivacaine HCl and H89 2HCl with permethrin were further examined in Culex mosquito larvae, providing a valuable new information for mosquito control strategies.

2007 ◽  
Vol 38 (6) ◽  
pp. 651-661 ◽  
Author(s):  
Y. Zhang ◽  
M. Xu ◽  
S. Zhang ◽  
L. Yan ◽  
C. Yang ◽  
...  

Background/ Aims: Lactate functions as a metabolic key player in cancer in various aspects. G-protein coupled receptor 81 (GPR81), a cell surface lactate receptor, is involved in the metabolism of lactate. However, only a few studies have been conducted on GPR81 expression in cancer, especially hepatocellular carcinoma (HCC). The present study aims to identify the clinical significance of GPR81 expression in HCC and its role as a prognostic factor. Methods: Tissues were obtained from 197 patients who had undergone surgery for HCC. GPR81 expression level was assessed by immunohistochemistry. And the function of GPR81 on HCC cell growth and mobility was explored through cell line studies. Results: GPR81 was overexpressed in the HepG2, Huh7, SNU182 and SK-Hep1 HCC cell lines and HCC tissues compared with that in the THLE-2 normal liver cell lines. Furthermore, high GPR81 expression levels were correlated significantly with disease recurrence. In addition, because of significant differences in cancer proliferation, migration, and invasion depending on the GPR81 expression level in various HCC cell line studies, GPR81 is believed to play a role in promoting aggressive cancer cell behavior. Conclusions: As such, GPR81 expression level was determined to be a useful prognostic factor for predicting HCC progression. The present study is the first to report on GPR81 expression in HCC and its significance. Henceforth, GPR81 is expected to become a highly valuable candidate for future target therapy.


2006 ◽  
Vol 20 (12) ◽  
pp. 3146-3164 ◽  
Author(s):  
Tom Krietsch ◽  
Maria Sofia Fernandes ◽  
Jukka Kero ◽  
Ralf Lösel ◽  
Maria Heyens ◽  
...  

Abstract The steroid hormone progesterone exerts pleiotrophic functions in many cell types. Although progesterone controls transcriptional activation through binding to its nuclear receptors, it also initiates rapid nongenomic signaling events. Recently, three putative membrane progestin receptors (mPRα, β, and γ) with structural similarity to G protein-coupled receptors have been identified. These mPR isoforms are expressed in a tissue-specific manner and belong to the larger, highly conserved family of progestin and adiponectin receptors found in plants, eubacteria, and eukaryotes. The fish mPRα has been reported to mediate progesterone-dependent MAPK activation and inhibition of cAMP production through coupling to an inhibitory G protein. To functionally characterize the human homologs, we established human embryonic kidney 293 and MDA-MB-231 cell lines that stably express human mPRα, β, or γ. For comparison, we also established cell lines expressing the mPRα cloned from the spotted seatrout (Cynoscion nebulosus) and Japanese pufferfish (Takifugu rubripes). Surprisingly, we found no evidence that human or fish mPRs regulate cAMP production or MAPK (ERK1/2 or p38) activation upon progesterone stimulation. Furthermore, the mPRs did not couple to a highly promiscuous G protein subunit, Gαq5i, in transfection studies or provoke Ca2+ mobilization in response to progesterone. Finally, we demonstrate that transfected mPRs, as well as endogenous human mPRα, localize to the endoplasmic reticulum, and that their expression does not lead to increased progestin binding either in membrane preparations or in intact cells. Our results therefore do not support the concept that mPRs are plasma membrane receptors involved in transducing nongenomic progesterone actions.


2012 ◽  
Vol 287 (43) ◽  
pp. 36305-36311 ◽  
Author(s):  
Ka Young Chung ◽  
Tae Hun Kim ◽  
Aashish Manglik ◽  
Rohan Alvares ◽  
Brian K. Kobilka ◽  
...  

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