caa a22 4500 475742982 CHVBK 20180406123505.0 cr unu---uuuuu 170329e20000401xx s 000 0 eng 10.1007/s002400050147 doi (NATIONALLICENCE)springer-10.1007/s002400050147 Relaxation of human ureteral smooth muscle in vitro by modulation of cyclic nucleotide-dependent pathways [Elektronische Daten] [Rainer Kühn, Stefan Ückert, Christian G. Stief, Michael C. Truss, Burckhard Lietz, Erwin Bischoff, Matthias Schramm, Udo Jonas] Phosphodiesterases (PDE) are key enzymes regulating intracellular cyclic nucleotide turnover and, thus, smooth muscle tension. Recent reports have indicated the presence of PDE isoenzymes 1, 2, 4, and 5 in cytosolic supernatants prepared from human ureteral smooth muscle homogenates and the ability of second-generation inhibitors of PDE 3, 4, and 5 to relax KCl-induced tension of human ureteral muscle in vitro. The aim of the present study was to evaluate the functional effects of recently developed, third-generation isoenzyme-selective PDE inhibitors, the nitric oxide (NO)-donating agents sodium nitroprusside (SNP) and dihydropyridine (DHP), which is also described as an antagonist of L-type calcium channels, and the adenylyl cyclase-stimulating drug forskolin on tissue tension and cyclic nucleotide levels of human ureteral smooth muscle segments in vitro. Relaxant responses of human ureteral smooth muscle were investigated in vitro using the organ bath technique. Cyclic nucleotides cAMP and cGMP were determined by specific radioimmunoassay following time and dose-dependent incubation of the ureteral tissue with the drugs. The most pronounced relaxing effects on KCl-induced tension of ureteral smooth muscle were exerted by nitrovasodilator SNP, PDE4 inhibitor rolipram, and PDE5 inhibitors E 4021 and morpholinosulfonyl-pyrazolopyrimidine (MSPP). Relaxing potency of the drugs was paralleled by their ability to elevate intracellular levels of cGMP and cAMP, respectively. Our data suggest the possibility of using selective inhibitors of PDE isoenzymes 4 and 5 in the treatment of ureteral stones and ureteral colic. Springer-Verlag Berlin Heidelberg, 2000 Key words Human ureter nationallicence Phosphodiesterases nationallicence Phosphodiesterase inhibitors nationallicence Cyclic nucleotide monophosphates nationallicence Kühn Rainer Hannover Medical School, Department of Urology, Carl-Neuberg-Str. 1, 30625 Hannover, Germany e-mail: stief.christian@mh-hannover.de Tel.: +49-511-5323437; Fax: +49-511-5328437, DE aut Ückert Stefan Hannover Medical School, Department of Urology, Carl-Neuberg-Str. 1, 30625 Hannover, Germany e-mail: stief.christian@mh-hannover.de Tel.: +49-511-5323437; Fax: +49-511-5328437, DE aut Stief Christian G. Hannover Medical School, Department of Urology, Carl-Neuberg-Str. 1, 30625 Hannover, Germany e-mail: stief.christian@mh-hannover.de Tel.: +49-511-5323437; Fax: +49-511-5328437, DE aut Truss Michael C. Hannover Medical School, Department of Urology, Carl-Neuberg-Str. 1, 30625 Hannover, Germany e-mail: stief.christian@mh-hannover.de Tel.: +49-511-5323437; Fax: +49-511-5328437, DE aut Lietz Burckhard St. Vincent Hospital, Department of Urology, 30559 Hannover, Germany, DE aut Bischoff Erwin Bayer AG, Pharmaceutical Division, 42113 Wuppertal, Germany, DE aut Schramm Matthias Bayer AG, Pharmaceutical Division, 42113 Wuppertal, Germany, DE aut Jonas Udo Hannover Medical School, Department of Urology, Carl-Neuberg-Str. 1, 30625 Hannover, Germany e-mail: stief.christian@mh-hannover.de Tel.: +49-511-5323437; Fax: +49-511-5328437, DE aut https://doi.org/10.1007/s002400050147 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s002400050147 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kühn Rainer Hannover Medical School, Department of Urology, Carl-Neuberg-Str. 1, 30625 Hannover, Germany e-mail: stief.christian@mh-hannover.de Tel.: +49-511-5323437; Fax: +49-511-5328437, DE aut NATIONALLICENCE 700 1- Ückert Stefan Hannover Medical School, Department of Urology, Carl-Neuberg-Str. 1, 30625 Hannover, Germany e-mail: stief.christian@mh-hannover.de Tel.: +49-511-5323437; Fax: +49-511-5328437, DE aut NATIONALLICENCE 700 1- Stief Christian G. Hannover Medical School, Department of Urology, Carl-Neuberg-Str. 1, 30625 Hannover, Germany e-mail: stief.christian@mh-hannover.de Tel.: +49-511-5323437; Fax: +49-511-5328437, DE aut NATIONALLICENCE 700 1- Truss Michael C. Hannover Medical School, Department of Urology, Carl-Neuberg-Str. 1, 30625 Hannover, Germany e-mail: stief.christian@mh-hannover.de Tel.: +49-511-5323437; Fax: +49-511-5328437, DE aut NATIONALLICENCE 700 1- Lietz Burckhard St. Vincent Hospital, Department of Urology, 30559 Hannover, Germany, DE aut NATIONALLICENCE 700 1- Bischoff Erwin Bayer AG, Pharmaceutical Division, 42113 Wuppertal, Germany, DE aut NATIONALLICENCE 700 1- Schramm Matthias Bayer AG, Pharmaceutical Division, 42113 Wuppertal, Germany, DE aut NATIONALLICENCE 700 1- Jonas Udo Hannover Medical School, Department of Urology, Carl-Neuberg-Str. 1, 30625 Hannover, Germany e-mail: stief.christian@mh-hannover.de Tel.: +49-511-5323437; Fax: +49-511-5328437, DE aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer