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Alpha1-adrenergic receptors activate Ca(2+)-permeable cationic channels in prostate cancer epithelial cells.

Abstract : The prostate gland is a rich source of alpha1-adrenergic receptors (alpha1-ARs). alpha1-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 alpha1-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 alpha1A subtype of adrenergic receptor (alpha1A-AR) and show its functional coupling to plasmalemmal cationic channels via direct diacylglycerol (DAG) gating. In both cell types, agonist-mediated stimulation of alpha1A-ARs and DAG analogues activated similar cationic membrane currents and Ca(2+) influx. These currents were sensitive to the alpha1A-AR antagonists, prazosin and WB4101, and to transient receptor potential (TRP) channel blockers, 2-aminophenyl borate and SK&F 96365. Chronic activation of alpha1A-ARs enhanced LNCaP cell proliferation, which could be antagonized by alpha1A-AR and TRP inhibitors. Collectively, our results suggest that alpha1-ARs play a role in promoting hPCE cell proliferation via TRP channels.
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https://www.hal.inserm.fr/inserm-00139765
Contributor : Matthieu Flourakis <>
Submitted on : Tuesday, April 3, 2007 - 4:17:52 PM
Last modification on : Wednesday, May 27, 2020 - 8:18:02 PM
Long-term archiving on: : Tuesday, April 6, 2010 - 11:21:54 PM

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Stéphanie Thébault, Morad Roudbaraki, Vadim Sydorenko, Yaroslav Shuba, Loic Lemonnier, et al.. Alpha1-adrenergic receptors activate Ca(2+)-permeable cationic channels in prostate cancer epithelial cells.. Journal of Clinical Investigation, American Society for Clinical Investigation, 2003, 111 (11), pp.1691-701. ⟨10.1172/JCI200316293.⟩. ⟨inserm-00139765⟩

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