Co-localization of alpha1-adrenoceptors and GPR55: a novel prostate cancer paradigm?

Patil, K. C., McPherson, L. and Daly, C. J. (2015) Co-localization of alpha1-adrenoceptors and GPR55: a novel prostate cancer paradigm? Pharmacology and Pharmacy, 6(4), pp. 212-220. (doi: 10.4236/pp.2015.64023)

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Publisher's URL: http://dx.doi.org/10.4236/pp.2015.64023

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 heterogeneous 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 fluorescent 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 incuba-tion. 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Daly, Professor Craig
Authors: Patil, K. C., McPherson, L., and Daly, C. J.
College/School:College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:Pharmacology and Pharmacy
Publisher:Scientific Publishing
ISSN:2157-9423
ISSN (Online):2157-9431
Copyright Holders:Copyright © 2015 The Authors and Scientific Research Publishing Inc.
First Published:First published in Pharmacology and Pharmacy 6(4):212-220
Publisher Policy:Reproduced under a Creative Commons License

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