Neurourology and Urodynamics 30:1388–1391 (2011) Exogenously Administered Bombesin and Gastrin Releasing Peptide Contract the Female Rat Urethra In Vivo and In Vitro P. Radziszewski, 1 * R. Crayton, 1,2 K. Persson, 3 K.-E. Andersson, 3 and A. Mattiasson 4 1 Department and Clinic of Urology, Faculty of Medical Sciences, Medical University of Warsaw, Warsaw, Poland 2 Department of Clinical and Experimental Physiology, Medical University of Warsaw, Warsaw, Poland 3 Clinical Pharmacology, Lund University Hospital, Lund, Sweden 4 Department of Urology, Lund University Hospital, Lund, Sweden Background: Bombesin (BOM) and gastrin releasing peptide (GRP) have been located to the lower urinary tract (LUT). However, there is a paucity of data demonstrating the impact of these endogenous peptides. Objectives: The aim of the present study was to investigate the contractile actions of BOM and GRP on the female rat urethra in vitro and in vivo. Female Sprague–Dawley rats (n ¼ 37) weighing approximately 225 g were used. Intraurethral pressure was recorded by a catheter placed at the maximum pressure zone corresponding to the intrinsic urethral sphincter. Measurements: In vitro, changes in intraurethral pressure was conducted on perfused intact urethral/bladder preparations and are expressed as percentages of sphincteric intraurethral pressure achieved with noradrenaline. In vivo, changes in intraurethral pressure was conducted in anesthetized subjects and compared with the baseline intraurethral pressure and sham controls. Results: In vitro, the increase in intraurethral pressure induced by BOM was 23.6 Æ 3.2 cmH 2 O, exceeding the pressure evoked with NA by 9.6 cmH 2 O or 174.4% whereas GRP induced a maximum pressure of 10.7 Æ 1.6 cmH 2 O, an increase of 2.2 Æ 0.5 cmH 2 O or 82.9% (P < 0.05) of the NA evoked pressure. In vivo, the mean baseline pressure was 22.9 Æ 1.4 cmH 2 O. The intraurethral pressure evoked by BOM was 50.6 Æ 6.3 cmH 2 O(P < 0.05), and for GRP, the evoked intraurethral pressure was 56.2 Æ 13.4 cmH 2 O(P < 0.05). Conclusions: The present data suggest that both BOM and GRP may contribute to the control of continence by their contractile action on the sphincters of the LUT outflow region. Neurourol. Urodynam. 30:1388–1391, 2011. ß 2011 Wiley-Liss, Inc. Key words: bombesin; gastrin releasing peptide; NANC; neuropeptides INTRODUCTION The biological effects of bombesin (BOM) and gastrin releasing peptide (GRP) include a broad range of important physiological and pathophysiological functions. 1,2 BOM and GRP exerted their effects via the neuromedin B receptor (BB1), the gastrin releasing peptide receptor (BB2), and the orphan bombesin receptor sub- type 3 (BB3). Several studies have reported the presence of the BOM neuropeptide and their respective receptors 3,4 in different parts of the lower urinary tract (LUT), such as the detrusor muscle, 5 the sphincteric region of rat urethra, 6 and the major pelvic ganglia of male rats. 7,8 It is well established that BOM can induce concentration-dependent contractions of human, rat, and guinea-pig urinary bladder smooth muscle without tachy- phylaxis. 9–15 However, it seems unlikely that this action con- tributes to the voiding contraction. 16 Whether or not the peptide may contribute to detrusor tone or serves some other purpose such as the maintenance of continence can only be speculated on. The presence and actions of various endogenous peptides in the urethra/urethral sphincter has been described in several in vitro and in vivo studies. 6,16–21 However, the effects of GRP and BOM on the urethra seems to be lacking. In the present study, the contractile actions of BOM and GRP on the female rat urethra in vitro and in vivo, using previously established methodology. 6 MATERIALS AND METHODS The experimental protocol was approved by the local Animal Ethics Committee for the University of Lund. Adult female Sprague–Dawley rats (n ¼ 37) weighing approximately 225 g were used in the study. The rats were kept two per standard laboratory cage and food and water was available ad libitum. The cage room was maintained with 12 hr dark/light phases with the dawn light phase from 7:00 am. Rats were randomly divided into their respective treatment groups. Drugs Noradrenaline (NA), phentolamine, indomethacin, BOM, and GRP were purchased from Sigma (St. Louis, MO), scopolamine (PerkinElmer, Waltham, MA), and pancuronuim (Pavulon, Organon, Holland). The drugs were diluted on the day of the experiment in bi-distilled water to their final concentrations. In Vitro Experiments The rats were euthanized using CO 2 asphyxia, and the bladder together with the urethra were dissected out en bloc and trans- ferred to ice-cold Krebs solution. Under an operating microscope, an incision was made in the bladder dome and an intraurethral catheter (Clay-Adams, PE-50 Parsippany, NJ) was introduced into Conflict of interest: none. Lori Birder led the review process. *Correspondence to: P. Radziszewski, Department of Urology, Medical University of Warsaw, Warszawa, Poland. E-mail: pradziszewski@wum.edu.pl Received 10 May 2010; Accepted 1 December 2010 Published online 29 June 2011 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/nau.21056 ß 2011 Wiley-Liss, Inc.