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Administration of imatinib mesylate in rats impairs the neonatal development of intramuscular interstitial cells in bladder and results in altered contractile properties
Author(s) -
Gevaert Thomas,
Hutchings Graham,
Everaerts Wouter,
Prenen Hans,
Roskams Tania,
Nilius Bernd,
De Ridder Dirk
Publication year - 2014
Publication title -
neurourology and urodynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 90
eISSN - 1520-6777
pISSN - 0733-2467
DOI - 10.1002/nau.22415
Subject(s) - medicine , contractility , immunohistochemistry , imatinib mesylate , urinary bladder , muscarinic acetylcholine receptor , endocrinology , receptor , imatinib , myeloid leukemia
Aims The KIT receptor is considered as a reliable marker for a subpopulation of interstitial cells (IC), and by persistent neonatal inhibition of KIT we have investigated the role of this receptor in the development of IC‐networks in bladder and we have observed the functional consequences of this inhibition. Methods Newborn rat pups were treated daily with the KIT inhibitor imatinib mesylate (IM). After 7 days animals were sacrificed and bladder samples were dissected for morphological and functional studies. Morphological research consisted of immunohistochemistry with IC specific antigens (KIT and vimentin) and electron microscopy. The functional studies were based on isolated bladder strips in organ baths, in which spontaneous bladder contractility and the response to a non‐subtype selective muscarinic agonist was evaluated. Results Suburothelial and intramuscular IC were found and characterized in neonatal rat bladder. IM‐treatment induced a significant decrease in numbers of IC based on specific immunohistochemical markers, and electron microscopy revealed evidence of IC cell injury. These morphological alterations were observed on intramuscular IC only and not on IC in the suburothelium. Isolated muscle strips from IM‐treated animals had a lower contractile frequency and an altered response to muscarinic agonists. Conclusions The present study shows the presence of regional subpopulations of IC in neonatal rat bladder, provides evidence for a dependence on KIT of the development of intramuscular IC and supports the hypothesis that a poor development of networks of intramuscular IC might have repercussions on spontaneous and muscarinic‐induced bladder contractility. Neurourol. Urodynam. 33:461–468, 2014 . © 2013 Wiley Periodicals, Inc.