α1-adrenergic receptors activate Ca2+-permeable cationic channels in prostate cancer epithelial cells
Stephanie Thebault, Morad Roudbaraki, Vadim Sydorenko, Yaroslav Shuba, Loic Lemonnier, Christian Slomianny, Etienne Dewailly, Jean-Louis Bonnal, Brigitte Mauroy, Roman Skryma, Natalia Prevarskaya
Stephanie Thebault, Morad Roudbaraki, Vadim Sydorenko, Yaroslav Shuba, Loic Lemonnier, Christian Slomianny, Etienne Dewailly, Jean-Louis Bonnal, Brigitte Mauroy, Roman Skryma, Natalia Prevarskaya
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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

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Phe and OAG activate cationic membrane current in LNCaP cells. (a and b)...
Phe and OAG activate cationic membrane current in LNCaP cells. (a and b) Superimposed recordings of the baseline current and current in the presence of Phe (50 μM) in representative LNCaP cells (a; pulse protocol is shown above the records) and I-V relationship of Phe-induced current derived from ramp portions of the recordings (b). (c) Phe-induced current (measured at –100 mV). Each trace shows mean ± SEM current density in response to Phe application (horizontal bar) (n = 9). The right-hand panel presents original baseline (top) and Phe-induced (bottom) currents recorded at the times marked by asterisks (pulse protocol is shown above the baseline currents). Superimposed recordings of the baseline current and current in the presence of Phe (50 μM) in representative LNCaP cell exposed to OAG (100 μM) (d) and corresponding I-V relationship (e).