Do β3-adrenoceptor agonists cause urinary bladder smooth muscle relaxation by inhibiting acetylcholine release?

Do β3-adrenoceptor agonists cause urinary bladder smooth muscle relaxation by inhibiting 1 acetylcholine release? 2 Focus on “Inhibition of cholinergic neurotransmission by β3-adrenoceptors depends on 3 adenosine release and A1 receptors activation in human and rat urinary bladder” 4 5 Katerina Okeke, Stavros Gravas, Martin C. Michel 6 7 8 Dept. of Pharmacology, Johannes Gutenberg University, Mainz, Germany 9 Dept. of Urology, University of Thessaly, Larissa, Greece 10 11 Address for correspondence: 12 Prof. Martin C. Michel 13 Dept. of Pharmacology 14 Johannes Gutenberg University 15 Obere Zahlbacher Str. 67 16 55131 Mainz, Germany 17 Phone +49-6131-179356 18 Fax +49-6131-179043 19 Mail: [email protected] 20 21 β3-Adrenoceptor (β3-AR) agonists such as mirabegron are a novel drug class to treat the 22 overactive bladder syndrome (OAB) (4). Classic concepts have assumed that β3-AR agonists 23 work by directly acting on a β3-AR located in the plasma membrane of smooth muscle cells in 24 the detrusor of the urinary bladder (15). Recently, this concept has been critiqued increasingly 25 (7) because mirabegron, the only β3-AR agonist currently in clinical use, has an EC50 for 26 Articles in PresS. Am J Physiol Renal Physiol (May 17, 2017). doi:10.1152/ajprenal.00215.2017