The receptor antagonist picotamide inhibits adrenergic and thromboxane-induced contraction of hyperplastic human prostate smooth muscle

• Published in: American journal of physiology. Renal physiology 2013-11, Vol.305 (10), p.F1383-F1390
• Main Authors: Hennenberg, Martin, Miljak, Marijan, Herrmann, Daniel, Strittmatter, Frank, Walther, Sebastian, Rutz, Beata, Hocaoglu, Yasemin, Kunit, Thomas, Schreiber, Andrea, Andersson, Karl-Erik, Stief, Christian G, Gratzke, Christian
• Format: Article
• Language: English
• Subjects: Adrenergic Agonists - pharmacology; Adrenergic alpha-1 Receptor Antagonists - pharmacology; Dose-Response Relationship, Drug; Electric Stimulation; Gene expression; Humans; Male; Muscle Contraction - drug effects; Muscle, Smooth - drug effects; Muscle, Smooth - innervation; Muscle, Smooth - metabolism; Phthalic Acids - pharmacology; Prostaglandin Antagonists - pharmacology; Prostate; Prostate - drug effects; Prostate - innervation; Prostate - metabolism; Receptors, Adrenergic, alpha-1 - drug effects; Receptors, Adrenergic, alpha-1 - metabolism; Receptors, Thromboxane A2, Prostaglandin H2 - antagonists & inhibitors; Receptors, Thromboxane A2, Prostaglandin H2 - metabolism; Signal Transduction - drug effects; T cell receptors; Thromboxane-A Synthase - metabolism; Thromboxanes - pharmacology; Tissues
• ISSN: 1931-857X; 1522-1466
• DOI: 10.1152/ajprenal.00380.2013

Inhibition of prostate smooth muscle contraction is an important strategy for medical treatment of lower urinary tract symptoms (LUTS). Besides α1-adrenoceptors, prostate smooth muscle contraction is induced by activation of thromboxane (TXA2) receptors (TXA2-R). Here, we examined the effects of the TXA2-R antagonist picotamide on contraction of human prostate tissue. Prostate tissues were obtained from radical prostatectomy. The effects of picotamide (300 μM), L-665,240 (3 μM), and seratrodast (3 μM) on U46619-, electric field stimulation- (EFS-), phenylephrine-, and norepinephrine-induced contractions were studied in organ baths. Expression of TXA2-R and TXA2 synthase (TXS) was examined by fluorescence stainings. Picotamide, seratrodast, and L-655,240 inhibited concentration-dependent contractions induced by the TXA2 analog U46619. Picotamide, but not seratrodast or L-655,240, inhibited frequency-dependent contractions induced by EFS. Picotamide inhibited concentration-dependent contractions induced by norepinephrine or by the selective α1-adrenoceptor agonist phenylephrine. In prostate strips, where only submaximal contraction by a low dose of phenylephrine was induced, application of U46619 raised tone to maximum phenylephrine-induced tension. Immunoreactivity for TXA2-R and TXS was observed in the stroma and in epithelial cells of glands. Colocalization of both immunoreactivites was observed with the smooth muscle markers calponin and α-smooth muscle actin, with the epithelial marker pan-cytokeratin, and with prostate-specific antigen in the stroma and glands. The receptor antagonist picotamide inhibits α1-adrenergic, TXA2-mediated, and EFS-induced contractions in the human prostate. To the best of our knowledge, this is the first antagonist able to inhibit two different contraction systems in the prostate.