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447 Micturition is controlled by neuronal cannabinoid receptor type 1 – a urodynamic evaluation of a CB1 knockout mouse model
447
Micturition is controlled by neuronal cannabinoid receptor type 1 – a urodynamic evaluation of a CB1 knockout mouse model Eur Urol Suppl 2013;12;e447
Fullhase C.1, Campeau L.2, Sibaev A.3, Storr M.3, Gratzke C.1, Stief C.1, Hedlund P.4, Andersson K.E.5 1Ludwig Maximilians University, Dept. of Urology, Munich, Germany, 2Wake Forest University, Dept. of Urology Institute
For Regenerative Medicine, Winston-Salem, United States of America, 3Ludwig Maximilians University, Dept. of Internal Medicine, Munich, Germany, 4San Raffaele University, Urological Research Institute, Milan, Italy, 5Wake Forest University, Institute For Regenerative MedicineDept. of Urology, Winston-Salem, United States of America INTRODUCTION & OBJECTIVES: Currently the role of the cannabinoid system in micturition is being evaluated. CB1 as well as CB2 receptor agonists, and fatty acid amide hydrolase (FAAH) inhibitors, which inhibit the degradation of endocannabinoids, are developed as potential new drugs in the treatment of various voiding disorders, such as OAB and LUTS. However, the contribution and importance of different CB receptors for micturition has not yet been established. The present work aimed to characterize a CB1 knockout mouse to examine the role of the CB1 receptor in micturition. MATERIAL & METHODS: Twenty CB1 knockout (KO) mice and 20 wildtype (WT) mice (strain C57BL/6) were used for organ bath and urodynamic experiments. In organ bath experiments bladder strips were exposed to KCl, carbachol (response curve 0.1 – 100 μmol), and to electrical field stimulation (2 – 32 Hz) to assess muscular (pharmacological) and neurogenic (electrical) contractions. For urodynamic experiments bladder catheters were implanted via an abdominal incision and tunneled subcutaneous to the neck. Cystometry, without anesthesia, was performed three days following operation. The following parameters were assessed: intermicturition interval (IMI), bladder capacity (BCap), micturition volume (MV), residual volume (RV), basal (BP), threshold (TP), and maximum (MP) bladder pressure, spontaneous bladder activity (SA), and bladder compliance (BCom). RESULTS: Bladder strips from CB1 KO mice did not react differently than WT upon pharmacological stimulation in the organ bath, but hey showed significant weaker responses upon electrical stimulation. WT mice showed IMI 7.32 ±0.50 min, BCap 0.18 ±0.01 mL, MV 0.14 ±0.01 mL, RV 0.05 ±0.01 mL, BP 7.4 ±0.5 cmH2O, TP 17.1 ±0.7 cmH2O, MP 39.5 ±2.4 cmH2O, SA 2.6 ±0.6 cmH2O, and BCom 0.020 ±0.002 mL/cmH2O. CB1 KO mice had IMI 3.24 ±0.29 min, BCap 0.09 ±0.01 mL, MV 0.07 ±0.01 mL, RV 0.02 ±0.01 mL, BP 5.8 ±0.6 cmH2O, TP 19.7 ±1.8 cmH2O, MP 44.1 ±5.6 cmH2O, SA 5.1 ±0.5 cmH2O, and BCom 0.007 ±0.001 mL/cmH2O. Those different urodynamic parameters were significant (p < 0.001; ttest) for IMI, BCap, MV, SA, and BCom. CONCLUSIONS: CB1 KO mice show an increased micturition frequency and spontaneous bladder activity compared to WT mice. In organ bath experiments CB1 KO mice bladders respond less to electrical, but not different to pharmacological, stimulation. These differences suggest that CB1 receptors are involved in the micturition process, and affect micturition rather via a neuronal site than through direct effects on the detrusor.
Micturition is controlled by neuronal cannabinoid receptor type 1 – a urodynamic evaluation of a CB1 knockout mouse model Eur Urol Suppl 2013;12;e447
Fullhase C.1, Campeau L.2, Sibaev A.3, Storr M.3, Gratzke C.1, Stief C.1, Hedlund P.4, Andersson K.E.5 1Ludwig Maximilians University, Dept. of Urology, Munich, Germany, 2Wake Forest University, Dept. of Urology Institute
For Regenerative Medicine, Winston-Salem, United States of America, 3Ludwig Maximilians University, Dept. of Internal Medicine, Munich, Germany, 4San Raffaele University, Urological Research Institute, Milan, Italy, 5Wake Forest University, Institute For Regenerative MedicineDept. of Urology, Winston-Salem, United States of America INTRODUCTION & OBJECTIVES: Currently the role of the cannabinoid system in micturition is being evaluated. CB1 as well as CB2 receptor agonists, and fatty acid amide hydrolase (FAAH) inhibitors, which inhibit the degradation of endocannabinoids, are developed as potential new drugs in the treatment of various voiding disorders, such as OAB and LUTS. However, the contribution and importance of different CB receptors for micturition has not yet been established. The present work aimed to characterize a CB1 knockout mouse to examine the role of the CB1 receptor in micturition. MATERIAL & METHODS: Twenty CB1 knockout (KO) mice and 20 wildtype (WT) mice (strain C57BL/6) were used for organ bath and urodynamic experiments. In organ bath experiments bladder strips were exposed to KCl, carbachol (response curve 0.1 – 100 μmol), and to electrical field stimulation (2 – 32 Hz) to assess muscular (pharmacological) and neurogenic (electrical) contractions. For urodynamic experiments bladder catheters were implanted via an abdominal incision and tunneled subcutaneous to the neck. Cystometry, without anesthesia, was performed three days following operation. The following parameters were assessed: intermicturition interval (IMI), bladder capacity (BCap), micturition volume (MV), residual volume (RV), basal (BP), threshold (TP), and maximum (MP) bladder pressure, spontaneous bladder activity (SA), and bladder compliance (BCom). RESULTS: Bladder strips from CB1 KO mice did not react differently than WT upon pharmacological stimulation in the organ bath, but hey showed significant weaker responses upon electrical stimulation. WT mice showed IMI 7.32 ±0.50 min, BCap 0.18 ±0.01 mL, MV 0.14 ±0.01 mL, RV 0.05 ±0.01 mL, BP 7.4 ±0.5 cmH2O, TP 17.1 ±0.7 cmH2O, MP 39.5 ±2.4 cmH2O, SA 2.6 ±0.6 cmH2O, and BCom 0.020 ±0.002 mL/cmH2O. CB1 KO mice had IMI 3.24 ±0.29 min, BCap 0.09 ±0.01 mL, MV 0.07 ±0.01 mL, RV 0.02 ±0.01 mL, BP 5.8 ±0.6 cmH2O, TP 19.7 ±1.8 cmH2O, MP 44.1 ±5.6 cmH2O, SA 5.1 ±0.5 cmH2O, and BCom 0.007 ±0.001 mL/cmH2O. Those different urodynamic parameters were significant (p < 0.001; ttest) for IMI, BCap, MV, SA, and BCom. CONCLUSIONS: CB1 KO mice show an increased micturition frequency and spontaneous bladder activity compared to WT mice. In organ bath experiments CB1 KO mice bladders respond less to electrical, but not different to pharmacological, stimulation. These differences suggest that CB1 receptors are involved in the micturition process, and affect micturition rather via a neuronal site than through direct effects on the detrusor.