Alpha1-adrenergic receptors activate Ca(2+)-permeable cationic channels in prostate cancer epithelial cells.
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.
Thebault
Stephanie
S
Laboratoire de Physiologie Cellulaire, Institut National de la Santé et de la Recherche Médicale (INSERM) EMI 0228, Villeneuve d'Ascq, France.
Roudbaraki
Morad
M
Sydorenko
Vadim
V
Shuba
Yaroslav
Y
Lemonnier
Loic
L
Slomianny
Christian
C
Dewailly
Etienne
E
Bonnal
Jean-Louis
JL
Mauroy
Brigitte
B
Skryma
Roman
R
Prevarskaya
Natalia
N
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
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