PT  - JOURNAL ARTICLE
AU  - Daniel Giglio
AU  - Lucie Podmolíková
AU  - Gunnar Tobin
TI  - Changes in the Neuronal Control of the Urinary Bladder in a Model of Radiation Cystitis
AID  - 10.1124/jpet.117.246371
DP  - 2018 May 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 327--335
VI  - 365
IP  - 2
4099  - http://jpet.aspetjournals.org/content/365/2/327.short
4100  - http://jpet.aspetjournals.org/content/365/2/327.full
SO  - J Pharmacol Exp Ther2018 May 01; 365
AB  - Currently, we have assessed the neuronal control of the urinary bladder in radiation cystitis and whether interstitial cells contribute to the condition. Fourteen days after bladder irradiation (20 Gy), rats were sedated and the urinary bladder was cut into two sagittal halves where electrical field stimulation (EFS; 5–20 Hz) was applied on the pelvic nerve afferents or stretch (80 mN) on one-half of the bladder, while contractions were registered on the contralateral half of the bladder in the absence and presence of increasing doses of imatinib (1–10 mg/kg; inhibitor of c-kit–positive interstitial cells), atropine (1 mg/kg; to block muscarinic M3 receptors), or pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid (2 mg/kg; P2X1 purinoceptor antagonist). Urinary bladders were also excised for organ bath experiments, Western blot, quantitative polymerase chain reaction, and immunohistochemistry. In vivo, EFS contractions were enhanced after irradiation, and imatinib (1–10 mg/mg) inhibited contractions by EFS and stretched dose-dependently in controls but not in irradiated bladders. In the irradiated bladder in vitro, atropine resistance was increased and imatinib (100 µM) inhibited contractions by EFS and agonists (ATP, methacholine) in irradiated bladders and controls. The urinary bladder expressions of P2X1 purinoceptors, muscarinic M3 receptor, choline acetyltransferase, c-kit, and the agonist of c-kit, stem cell factor, were not changed by irradiation. In conclusion, bladder irradiation affects several levels of neuronal control of the urinary bladder. Interstitial cells may contribute to some of the symptoms associated with radiation cystitis.