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Patil, Kalyani Chimajirao; McPherson, Laura; Daly, Craig James (2015)
Publisher: Scientific Publishing
Languages: English
Types: Article
Subjects:
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.
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    • Russell, P.J. and Kingsley, E.A. (2003) Human Prostate Cancer Cell Lines. Methods in Molecular Medicine Prostate Cancer Methods and Protocols, 81, 21-39. http://dx.doi.org/10.1385/1-59259-372-0:21 Isaacs, J.T. (1994) The Role of Androgens in Prostatic Cancer. Vitamins & Hormones, 49, 433-502. http://dx.doi.org/10.1016/S0083-6729(08)61152-8
    • Crawford, E.D., Eisenberger, M.A., McLeod, D.C., Spaulding, J., Benson, R., Dorr, F.A., Blumenstein, B.A., Davis, M.A. and Goodman, P.J. (1989) A Controlled Randomized Trial of Leuprolide with and without Flutamide in Prostatic Cancer. New England Journal of Medicine, 321, 419-424. http://dx.doi.org/10.1056/NEJM198908173210702 Daaka, Y.G. (2004) Proteins in Cancer: The Prostate Cancer Paradigm. Sci STKE, 216, 1-10. Hennenberg, M., Stief, C.G. and Gratzke, C. (2014) Prostatic a1-adrenoceptors: New Concepts of Function, Regulation, and Intracellular Signaling. Neurology & Urodynamics, 33, 1074-1085. http://dx.doi.org/10.1002/nau.22467 Kyprianou, N., Chon, J. and Benning, C.M. (2000) Effects of Alpha1-Adrenoceptor (α1-AR) Antagonists on Cell Proliferation and Apoptosis in the Prostate: Therapeutic Implications in Prostatic Disease. The Prostate Supplement, 9, 42-46. http://dx.doi.org/10.1002/1097-0045(2000)45:9+<42::AID-PROS9>3.0.CO;2-U
    • Desiniotis, A. and Kyprianou, N. (2011) Advances in the Design and Synthesis of Prazosin Derivatives over the Last Ten Years. Expert Opinion on Therapeutic Targets, 15, 1405-1418. http://dx.doi.org/10.1517/14728222.2011.641534 Gray, K., Short, J. and Ventura, S. (2008) The α1A-Adrenoceptor Gene Is Required for the α1L-Adrenoceptor-Mediated Response in Isolated Preparations of the Mouse Prostate. British Journal of Pharmacology, 155, 103-109. http://dx.doi.org/10.1038/bjp.2008.245
    • Kyprianou, N., Litvak, J., Alexander, R.B., Borkowski, A. and Jacobs, S.C. (1998) Induction of Prostate Apoptosis by Doxazosin. Journal of Urology, 159, 1810-1815. http://dx.doi.org/10.1016/S0022-5347(01)63162-8
    • [10] Chon, J., Isaacs, J.T., Borkowski, A., Partin, A.W., Jacobs, S.C. and Kyprianou, N. (1999) α-1 Adrenoceptor Antagonists Terazosin and Doxazosin Induce Prostate Apoptosis without Affecting Cell Proliferation in Patients with Benign Prostatic Hyperplasia. Journal of Urology, 161, 2002-2008. http://dx.doi.org/10.1016/S0022-5347(05)68873-8
    • [11] Harris, A.M., Warner, B.W., Wilson, J.M., Becker, A., Rowland, R.G., Conner, W., Lane, M., Kimbler, K., Durbin, E.B., Baron, A.T. and Kyprianou, N. (2007) Effect of α1-Adrenoceptor Antagonist Exposure on Prostate Cancer Incidence: An Observational Cohort Study. The Journal of Urology, 178, 2176-2180. http://dx.doi.org/10.1016/j.juro.2007.06.043
    • [12] Kyprianou, N. (2003) Doxazosin and Terazosin Suppress Prostate Growth by Inducing Apoptosis: Clinical Significance. The Journal of Urology, 169, 1520-1525. http://dx.doi.org/10.1097/01.ju.0000033280.29453.72
    • [13] Walden, P.D., Globina, Y. and Nieder, A. (2004) Induction of Anoikis by Doxazosin in Prostate Cancer Cells Is Associated with Activation of Caspase-3 and a Reduction of Focal Adhesion Kinase. Urological Research, 32, 261-265. http://dx.doi.org/10.1007/s00240-003-0365-7
    • [14] Garrison, J. and Kyprianou, N. (2006) Doxazosin Induces Apoptosis of Benign and Malignant Prostate Cells via a Death Receptor-Mediated Pathway. Cancer Research, 66, 464-472. http://dx.doi.org/10.1158/0008-5472.CAN-05-2039
    • [15] Henstridge, C.M. (2012) Off-Target Cannabinoid Effects Mediated by GPR55. Pharmacology, 89, 179-187. http://dx.doi.org/10.1159/000336872
    • [16] Chung, S.C., Hammarsten, P., Josefsson, A., Stattin, P., Granfors, T. and Egevad, L. (2009) A High Cannabinoid CB1 Receptor Immune-Reactivity Is Associated with Disease Severity and Outcome in Prostate Cancer. European Journal of Cancer, 45, 174-182. http://dx.doi.org/10.1016/j.ejca.2008.10.010
    • [17] Melck, D., Rueda, D., Galve-Roperh, I., De Petrocellis, L., Guzmán, M. and Di Marzo, V. (1999) Involvement of the cAMP/Protein Kinase A Pathway and of Mitogen-Activated Protein Kinase in the Anti-Proliferative Effects of Anandamide in Human Breast Cancer Cells. FEBS Letters, 463, 235-240. http://dx.doi.org/10.1016/S0014-5793(99)01639-7
    • [18] Sánchez, M.G., Ruiz-Llorente, L., Sánchez, A.M. and Díaz-Laviada, I. (2003) Activation of Phosphoinositide 3-Kinase/PKB Pathway by CB1 and CB2 Cannabinoid Receptors Expressed in Prostate PC-3 Cells: Involvement in Raf-1 Stimulation and NGF Induction. Cellular Signalling, 15, 851-859. http://dx.doi.org/10.1016/S0898-6568(03)00036-6
    • [19] Nithipatikom, K., Endsley, M.P., Isbell, M.A., Falck, J.R., Iwamoto, Y., Hillard, C.J. and Campbell, W. (2004) 2-Arachidonoylglycerol: A Novel Inhibitor of Androgen-Independent Prostate Cancer Cell Invasion. Cancer Research, 64, 8826-8830. http://dx.doi.org/10.1158/0008-5472.CAN-04-3136
    • [20] Sarfaraz, S., Afaq, F., Adhami, V.M. and Mukhtar, H. (2005) Cannabinoid Receptor as a Novel Target for the Treatment of Prostate Cancer. Cancer Research, 65, 1635-1641. http://dx.doi.org/10.1158/0008-5472.CAN-04-3410
    • [21] Brown, I., Cascio, M.G., Wahle, K.W., Smoum, R., Mechoulam, R. and Ross, R.A. (2010) Cannabinoid Receptor-Dependent and -Independent Anti-Proliferative Effects of Omega-3 Ethanolamides in Androgen Receptor-Positive and -Negative Prostate Cancer Cell Lines. Carcinogenesis, 31, 1584-1591. http://dx.doi.org/10.1093/carcin/bgq151
    • [22] Andradas, C., Caffarel, M.M., Perez-Gomez, E., Salazar, M., Lorente, M., Velasco, G., Guzman, M. and Sanchez, M. (2011) The Orphan G Protein-Coupled Receptor GPR55 Promotes Cancer Cell Proliferation via ERK. Oncogene, 30, 245-252. http://dx.doi.org/10.1038/onc.2010.402
    • [23] Bondarenko, A., Waldeck-Weiermair, M., Naghdi, S., Poteser, M., Malli, R. and Graier, W. (2010) GPR55-Dependent and -Independent Ion Signaling in Response to Lysophosphatidylinositol in Endothelial Cells. British Journal of Pharmacology, 161, 308-320. http://dx.doi.org/10.1111/j.1476-5381.2010.00744.x
    • [24] Daly, C.J., Ross, R.A., Whyte, J., Henstridge, C.M., Irving, A.J. and McGrath, J.C. (2010) Fluorescent Ligand Binding Reveals Heterogeneous Distribution of Adrenoceptors and “Cannabinoid-Like” Receptors in Small Arteries. British Journal of Pharmacology, 159, 787-796. http://dx.doi.org/10.1111/j.1476-5381.2009.00608.x
    • [25] Daly, C.J., Milligan, C.M., Milligan, G., Mackenzie, J.F. and Mcgrath, J.C. (1998) Cellular Localization and Pharmacological Characterization of Functioning Alpha-1 Adrenoceptors by Fluorescent Ligand Binding and Image Analysis Reveals Identical Binding Properties of Clustered and Diffuse Populations of Receptors. The Journal of Pharmacology and Experimental Therapeutics, 286, 984-990.
    • [26] Hudson, B.D., Hébert, T.E. and Kelly, M. (2010) Physical and Functional Interactions between CB1 Cannabinoid Receptors and β2-Adrenocepors. British Journal of Pharmacology, 160, 627-642. http://dx.doi.org/10.1111/j.1476-5381.2010.00681.x
    • [27] Daly, C.J. and McGrath, J.C. (2011) Previously Unsuspected Widespread Cellular and Tissue Distribution of Beta-Adrenoceptors and Its Relevance to Drug Action. Trends in Pharmacological Sciences, 32, 219-226. http://dx.doi.org/10.1016/j.tips.2011.02.008
    • [28] Angers, S., Salapour, A. and Bouvier, M. (2002) Dimerization: An Emerging Concept for G Protein-Coupled Receptor Ontogeny and Function. Annual Review of Pharmacology and Toxicology, 42, 409-435. http://dx.doi.org/10.1146/annurev.pharmtox.42.091701.082314
    • [29] Milligan, G., Pediani, J., Fidock, M. and López-Giménez, J.F. (2004) Dimerization of Alpha1-Adrenoceptors. Biochemical Society Transactions, 32, 847-850.
    • [30] Uberti, M., Hague, C., Oller, H., Minneman, K. and Hall, R. (2005) Heterodimerisation with β2-Adrenergic Receptors Promotes Surface Expression and Functional Activity of α1D-Adrenergic Receptors. Journal of Pharmacology and Experimental Therapeutics, 313, 16-23. http://dx.doi.org/10.1124/jpet.104.079541
    • [31] Copik, A.J., Ma, C., Kosaka, A., Sahdeo, S., Trane, A., Ho, H., Dietrich, P.S., Yu, H., Ford, A.P., Button, D. and Milla, M.E. (2009) Facilitatory Interplay in α1a and β2 Adrenoceptor Function Reveals a Non-Gq Signaling Mode: Implications for Diversification of Intracellular Signal Transduction. Molecular Pharmacology, 75, 713-728. http://dx.doi.org/10.1124/mol.108.050765
    • [32] Pennefather, J.N., Lau, W.A., Mitchelson, F. and Ventura, S. (2000) The Autonomic and Sensory Innervation of the Smooth Muscle of the Prostate Gland: A Review of Pharmacological and Histological Studies. Journal of Autonomic Pharmacology, 20, 193-206. http://dx.doi.org/10.1046/j.1365-2680.2000.00195.x
    • [33] Aarons, R.D., Nies, A.S., Gal, J., Hegstrand, L.R. and Molinoff, P.B. (1980) Elevation of Beta-Adrenergic Receptor Density in Human Lymphocytes after Propranolol Administration. Journal of Clinical Investigation, 65, 949-957. http://dx.doi.org/10.1172/JCI109781
    • [34] Foster Jr., H.E., Yono, M., Shin, D., Takahashi, W., Pouresmail, M., Afiatpour, P. and Latifpour, J. (2004) Effects of Chronic Administration of Doxazosin on α1-Adrenoceptors in the Rat Prostate. The Journal of Urology, 172, 2465- 2470. http://dx.doi.org/10.1097/01.ju.0000138475.89790.88
    • [35] Yono, M., Poster Jr., H.E., Shin, D., Takahashi, W., Pouresmail, M. and Latifpour, J. (2004) Doxazosin Treatment Causes Differential Alterations of α1-Adrenoceptor Subtypes in the Rat Kidney, Heart and Aorta. Life Sciences, 75, 2605-2614. http://dx.doi.org/10.1016/j.lfs.2004.08.001
    • [36] 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.
    • [37] Schlicker, E., Timm, J., Zentner, J. and Gothert, M. (1997) Cannabinoid CB1 Receptor-Mediated Inhibition of Noradrenaline Release in the Human and Guinea-Pig Hippocampus. Naunyn-Schmiedeberg's Archives of Pharmacology, 356, 583-589. http://dx.doi.org/10.1007/PL00005093
    • [38] Schultheiss, T., Flau, K., Kathmann, M., Gothert, M. and Schlicker, E. (2005) Cannabinoid CB1 Receptor-Mediated Inhibition of Noradrenaline Release in Guinea-Pig Vessels, but Not in Rat and Mouse Aorta. Naunyn-Schmiedeberg's Archives of Pharmacology, 372, 139-146. http://dx.doi.org/10.1007/s00210-005-0007-4
    • [39] Pakdeechote, P., Dunn, W.R. and Ralevic, V. (2007) Cannabinoids Inhibit Noradrenergic and Purinergic Sympathetic Cotransmission in the Rat Isolated Mesenteric Arterial Bed. British Journal of Pharmacology, 152, 725-733. http://dx.doi.org/10.1038/sj.bjp.0707397
    • [40] Tam, J., Trembovler, V., Di Marzo, V., Petrosino, S., Leo, G., Alexandrovich, A., Regev, E., Casap, N., Shteyer, A., Ledent, C., Karsak, M., Zimmer, A., Mechoulam, R., Yirmiya, R., Shohami, E. and Bab, I. (2008) The Cannabinoid CB1 Receptor Regulates Bone Formation by Modulating Adrenergic Signaling. The FASEB Journal, 22, 285-294. http://dx.doi.org/10.1096/fj.06-7957com
    • [41] Pineiro, R., Maffucci, T. and Falasca, M. (2011) The Putative Cannabinoid Receptor GPR55 Defines a Novel Autocrine Loop in Cancer Cell Proliferation. Oncogene, 30, 142-152. http://dx.doi.org/10.1038/onc.2010.417
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