α1-adrenergic receptors activate Ca2+-permeable cationic channels in prostate cancer epithelial cells
Stephanie Thebault, … , Roman Skryma, Natalia Prevarskaya
Stephanie Thebault, … , Roman Skryma, Natalia Prevarskaya
Published June 1, 2003
Citation Information: J Clin Invest. 2003;111(11):1691-1701. https://doi.org/10.1172/JCI16293.
View: Text | PDF
Article Aging

α1-adrenergic receptors activate Ca2+-permeable cationic channels in prostate cancer epithelial cells

Abstract

The prostate gland is a rich source of α1-adrenergic receptors (α1-ARs). α1-AR antagonists are commonly used in the treatment of benign prostatic hyperplasia symptoms, due to their action on smooth muscle cells. However, virtually nothing is known about the role of α1-ARs in epithelial cells. Here, by using two human prostate cancer epithelial (hPCE) cell models — primary cells from resection specimens (primary hPCE cells) and an LNCaP (lymph node carcinoma of the prostate) cell line — we identify an α1A subtype of adrenergic receptor (α1A-AR) and show its functional coupling to plasmalemmal cationic channels via direct diacylglycerol (DAG) gating. In both cell types, agonist-mediated stimulation of α1A-ARs and DAG analogues activated similar cationic membrane currents and Ca2+ influx. These currents were sensitive to the α1A-AR antagonists, prazosin and WB4101, and to transient receptor potential (TRP) channel blockers, 2–aminophenyl borate and SK&F 96365. Chronic activation of α1A-ARs enhanced LNCaP cell proliferation, which could be antagonized by α1A-AR and TRP inhibitors. Collectively, our results suggest that α1-ARs play a role in promoting hPCE cell proliferation via TRP channels.

Authors

Stephanie Thebault, Morad Roudbaraki, Vadim Sydorenko, Yaroslav Shuba, Loic Lemonnier, Christian Slomianny, Etienne Dewailly, Jean-Louis Bonnal, Brigitte Mauroy, Roman Skryma, Natalia Prevarskaya

×

Figure 2

Options: View larger image (or click on image) Download as PowerPoint
α1A-AR agonist–evoked Ca2+ signaling in human prostate epithelial cells....
α1A-AR agonist–evoked Ca2+ signaling in human prostate epithelial cells. (a and b) Changes in [Ca2+]i in representative primary human prostate epithelial cells in response to Phe (10 μM, n = 17) (a) alone and (b) in combination with SK&F 96365 (10 μM, n = 9). (c) Phe-evoked changes in [Ca2+]i in representative LNCaP cells under control conditions (n = 37) and in the presence of the α1-AR antagonists prazosin (n = 31) or WB4101 (n = 33) (both at 1 μM). (d) Phe-evoked [Ca2+]i increase in LNCaP cells at 2 mM extracellular Ca2+ (2/Ca2+) and the decrease on removal of extracellular Ca2+ (0/Ca2+) (n = 29). (e) Blockade of Phe-evoked [Ca2+]i increase in two representative LNCaP cells by SK&F 96365 (10 μM, n = 10) and 2-APB (100 μM, n = 10). [Ca2+]i signals were measured on Fura-2–loaded cells; all interventions in each panel are marked by horizontal bars.