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Changes in the Neuronal Control of the Urinary Bladder in a Model of Radiation Cystitis.

Journal article
Authors Daniel Giglio
Lucie Podmolíková
Gunnar Tobin
Published in The Journal of pharmacology and experimental therapeutics
Volume 365
Issue 2
Pages 327-335
ISSN 1521-0103
Publication year 2018
Published at Institute of Clinical Sciences, Department of Oncology
Institute of Neuroscience and Physiology, Department of Pharmacology
Pages 327-335
Language en
Links dx.doi.org/10.1124/jpet.117.246371
www.ncbi.nlm.nih.gov/entrez/query.f...
Subject categories Pharmacology

Abstract

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 M3receptors), or pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (2 mg/kg; P2X1purinoceptor 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 (100µM) inhibited contractions by EFS and agonists (ATP, methacholine) in irradiated bladders and controls. The urinary bladder expressions of P2X1purinoceptors, muscarinic M3receptor, 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.

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Utskriftsdatum: 2019-12-14