title: 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.
authors.affiliation: Laboratoire de Physiologie Cellulaire, Institut National de la Santé et de la Recherche Médicale (INSERM) EMI 0228, Villeneuve d'Ascq, France.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Thebault
authors.forename: Morad
authors.initials: M
authors.lastname: Roudbaraki
authors.forename: Vadim
authors.initials: V
authors.lastname: Sydorenko
authors.forename: Yaroslav
authors.initials: Y
authors.lastname: Shuba
authors.forename: Loic
authors.initials: L
authors.lastname: Lemonnier
authors.forename: Christian
authors.initials: C
authors.lastname: Slomianny
authors.forename: Etienne
authors.initials: E
authors.lastname: Dewailly
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Bonnal
authors.forename: Brigitte
authors.initials: B
authors.lastname: Mauroy
authors.forename: Roman
authors.initials: R
authors.lastname: Skryma
authors.forename: Natalia
authors.initials: N
authors.lastname: Prevarskaya
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D015153:Blotting, Western; D001896:Boron Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002412:Cations; D002455:Cell Division; D004075:Diglycerides / Q000378:metabolism; D004146:Dioxanes / Q000494:pharmacology; D004594:Electrophysiology; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D008856:Microscopy, Fluorescence; D011224:Prazosin / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000378:metabolism*; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D001896:Boron Compounds; D002121:Calcium Channel Blockers; D002412:Cations; D004075:Diglycerides; D004146:Dioxanes; D007093:Imidazoles; D018340:Receptors, Adrenergic, alpha-1; C109986:2-aminoethoxydiphenyl borate; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D002118:Calcium; D011224:Prazosin