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Kreda, S.M., Sumner, M., Fillo, S., Ribeiro, C.M., Luo, G.X., Xie, W., Daniel, K.W., Shears, S., Collins, S. and Wetsel, W.C. (2001) α1-Adrenergic Receptors Mediate LH-Releasing Hormone Secretion through Phospholipases C and A2 in Immortalized Hypothalamic Neurons. Endocrinology, 142, 4839-4851.

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• TITLE: Co-Localization of Alpha1-Adrenoceptors and GPR55: A Novel Prostate Cancer Paradigm?

  AUTHORS: Kalyani Chimajirao Patil, Laura McPherson, Craig James Daly

  KEYWORDS: Prostate, α1-Adrenoceptor, GPR55, Doxazosin

  JOURNAL NAME: Pharmacology & Pharmacy, Vol.6 No.4, April 3, 2015

  ABSTRACT: α1-adrenoceptors (α1-ARs) and “cannabinoid-like” G Protein Coupled Receptor 55 (GPR55) belong to the G-protein coupled receptor (GPCR) family and play a crucial role in regulating prostate function. Although physical and functional interactions between the cannabinoid and adrenergic systems have been reported, analysis of functional interactions between α1-AR and GPR55 in normal and neoplastic prostate has not been reported. Since GPR55 levels are high in rodent adrenal gland, we propose a function link between the adrenergic system and GPR55 receptor. Confocal Laser Scanning Microscopy (CLSM) was employed to examine the endogenous α1-AR and GPR55 expression and their co-localization, expressed as fluorescence, in vitro in human andro-gen-insensitive PC-3 and androgen-sensitive LNCaP prostatic carcinoma cell lines, using the fluo-rescent ligands—Syto 62 (nuclear stain), BODIPY FL-Prazosin (QAPB; fluorescent quinazoline α1-AR ligand) and Tocriflour (T1117; a novel fluorescent diarylpyrazole cannabinoid/GPR55 ligand). Fluorescent ligand binding in untreated PC-3 cells and LNCaP cells and spheroids showed hetero-geneous expression of both α1-ARs and GPR55. A small proportion of cells had both α1-ARs and GPR55 in relatively equal numbers indicating a degree of co-localization. Co-localization of fluo-rescent ligand binding exhibited a stronger correlation in LNCaP (0.87) as compared to PC-3 (0.63) cells. Upregulation of α1-AR was observed in PC-3 cells following chronic doxazosin incubation. Robust T1117 binding, suggestive of GPR55 upregulation, was also observed in these cells. The presence of subtype-rich cells with a degree of co-localization between α1-ARs and GPR55 indicates a possibility for dimerisation or functional interaction and a new paradigm for functional synergism in which interactions may be either between cells or involve converging intracellular signaling processes.