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

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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