Tags

Type your tag names separated by a space and hit enter

Inhibition of agonist-induced smooth muscle contraction by picotamide in the male human lower urinary tract outflow region.
Eur J Pharmacol. 2017 May 15; 803:39-47.EJ

Abstract

Male lower urinary tract symptoms (LUTS) due to bladder outlet obstruction are characterized by abnormal smooth muscle contractions in the lower urinary tract. Alpha1-adrenoceptor antagonists may induce smooth muscle relaxation in the outflow region and represent the current gold standard of medical treatment. However, results may be unsatisfactory or inadequate. Apart from α1-adrenoceptor agonists, smooth muscle contraction in the outflow region may be induced by thromboxane A2 (TXA2), endothelins, or muscarinic receptor agonists. Here, we studied effects of the thromboxane A2 receptor (TP receptor) antagonist picotamide on contraction in the human male bladder trigone and prostate. Carbachol, the α1-adrenoceptor agonist phenylephrine, the thromboxane A2 analog U46619, and electric field stimulation (EFS) induced concentration- or frequency-dependent contractions of trigone tissues in an organ bath. Picotamide (300µM) inhibited carbachol-, phenylephrine-, U46619-, and EFS-induced contractions. Endothelins 1-3 induced concentration-dependent contractions of prostate tissues, which were inhibited by picotamide. Analyses using real time polymerase chain reaction and antibodies suggested expression of thromboxane A2 receptors and synthase in trigone smooth muscle cells. Thromboxane B2 (the stable metabolite of thromboxane A2) was detectable by enzyme immune assay in trigone samples, with most values ranging between 50 and 150pg/mg trigone protein. Picotamide inhibits contractions induced by different stimuli in the human lower urinary tract, including cholinergic, adrenergic, thromboxane A2- and endothelin-induced, and neurogenic contractions in different locations of the outflow region. This distinguishes picotamide from current medical treatments for LUTS, and suggests that picotamide may induce urodynamic effects in vivo.

Authors+Show Affiliations

Department of Urology, Ludwig-Maximilians University, Munich, Germany.Department of Urology, Ludwig-Maximilians University, Munich, Germany.Department of Urology, Ludwig-Maximilians University, Munich, Germany.Department of Urology, Ludwig-Maximilians University, Munich, Germany.Department of Urology, Ludwig-Maximilians University, Munich, Germany.Department of Urology, Ludwig-Maximilians University, Munich, Germany.Department of Urology, Ludwig-Maximilians University, Munich, Germany.Department of Urology, Ludwig-Maximilians University, Munich, Germany.Department of Urology, Ludwig-Maximilians University, Munich, Germany.Department of Urology, Ludwig-Maximilians University, Munich, Germany.Department of Urology, Ludwig-Maximilians University, Munich, Germany.Department of Urology, Ludwig-Maximilians University, Munich, Germany. Electronic address: christian.gratzke@med.uni-muenchen.de.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28315343

Citation

Hennenberg, Martin, et al. "Inhibition of Agonist-induced Smooth Muscle Contraction By Picotamide in the Male Human Lower Urinary Tract Outflow Region." European Journal of Pharmacology, vol. 803, 2017, pp. 39-47.
Hennenberg M, Tamalunas A, Wang Y, et al. Inhibition of agonist-induced smooth muscle contraction by picotamide in the male human lower urinary tract outflow region. Eur J Pharmacol. 2017;803:39-47.
Hennenberg, M., Tamalunas, A., Wang, Y., Keller, P., Schott, M., Strittmatter, F., Herlemann, A., Yu, Q., Rutz, B., Ciotkowska, A., Stief, C. G., & Gratzke, C. (2017). Inhibition of agonist-induced smooth muscle contraction by picotamide in the male human lower urinary tract outflow region. European Journal of Pharmacology, 803, 39-47. https://doi.org/10.1016/j.ejphar.2017.03.022
Hennenberg M, et al. Inhibition of Agonist-induced Smooth Muscle Contraction By Picotamide in the Male Human Lower Urinary Tract Outflow Region. Eur J Pharmacol. 2017 May 15;803:39-47. PubMed PMID: 28315343.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of agonist-induced smooth muscle contraction by picotamide in the male human lower urinary tract outflow region. AU - Hennenberg,Martin, AU - Tamalunas,Alexander, AU - Wang,Yiming, AU - Keller,Patrick, AU - Schott,Melanie, AU - Strittmatter,Frank, AU - Herlemann,Annika, AU - Yu,Qingfeng, AU - Rutz,Beata, AU - Ciotkowska,Anna, AU - Stief,Christian G, AU - Gratzke,Christian, Y1 - 2017/03/14/ PY - 2016/12/14/received PY - 2017/03/08/revised PY - 2017/03/13/accepted PY - 2017/3/21/pubmed PY - 2017/11/29/medline PY - 2017/3/19/entrez KW - Benign prostatic hyperplasia (BPH) KW - Carbachol (PubChem CID 2551) KW - Lower urinary tract symptoms (LUTS) KW - Phenylephrine (PubChem CID 5284443) KW - Picotamide KW - Picotamide (PubChem CID 4814) KW - Prostate smooth muscle contraction KW - Tetrodotoxin (PubChem CID 6324668) KW - Thromboxane A2 KW - Trigone KW - U46619 (PubChem CID 16760624) SP - 39 EP - 47 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 803 N2 - Male lower urinary tract symptoms (LUTS) due to bladder outlet obstruction are characterized by abnormal smooth muscle contractions in the lower urinary tract. Alpha1-adrenoceptor antagonists may induce smooth muscle relaxation in the outflow region and represent the current gold standard of medical treatment. However, results may be unsatisfactory or inadequate. Apart from α1-adrenoceptor agonists, smooth muscle contraction in the outflow region may be induced by thromboxane A2 (TXA2), endothelins, or muscarinic receptor agonists. Here, we studied effects of the thromboxane A2 receptor (TP receptor) antagonist picotamide on contraction in the human male bladder trigone and prostate. Carbachol, the α1-adrenoceptor agonist phenylephrine, the thromboxane A2 analog U46619, and electric field stimulation (EFS) induced concentration- or frequency-dependent contractions of trigone tissues in an organ bath. Picotamide (300µM) inhibited carbachol-, phenylephrine-, U46619-, and EFS-induced contractions. Endothelins 1-3 induced concentration-dependent contractions of prostate tissues, which were inhibited by picotamide. Analyses using real time polymerase chain reaction and antibodies suggested expression of thromboxane A2 receptors and synthase in trigone smooth muscle cells. Thromboxane B2 (the stable metabolite of thromboxane A2) was detectable by enzyme immune assay in trigone samples, with most values ranging between 50 and 150pg/mg trigone protein. Picotamide inhibits contractions induced by different stimuli in the human lower urinary tract, including cholinergic, adrenergic, thromboxane A2- and endothelin-induced, and neurogenic contractions in different locations of the outflow region. This distinguishes picotamide from current medical treatments for LUTS, and suggests that picotamide may induce urodynamic effects in vivo. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/28315343/Inhibition_of_agonist_induced_smooth_muscle_contraction_by_picotamide_in_the_male_human_lower_urinary_tract_outflow_region_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(17)30191-7 DB - PRIME DP - Unbound Medicine ER -