Impairment of cholinergic bladder contractility in rat model of type I diabetes complicated by cystitis: Contribution of neurotransmitter-degrading ectoenzymes
| Autor: | Yaroslav M. Shuba, I. A. Vladimirova, Eugenia M. Kulieva, Natalia Prevarskaya, Ganna V. Sotkis, Yelyzaveta Y. Shuba, Igor B. Philyppov, Roman Skryma, Kseniya L. Gulak |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Urinary Bladder Neuromuscular transmission Gene Expression Regulation Enzymologic Contractility 03 medical and health sciences chemistry.chemical_compound Adenosine Triphosphate 0302 clinical medicine Internal medicine Cystitis Muscarinic acetylcholine receptor medicine Animals Rats Wistar Pharmacology Neurotransmitter Agents business.industry Purinergic receptor medicine.disease Acetylcholinesterase Acetylcholine Rats Disease Models Animal Diabetes Mellitus Type 1 030104 developmental biology Endocrinology chemistry Cholinergic Extracellular Space business 030217 neurology & neurosurgery Muscle Contraction Hemorrhagic cystitis medicine.drug |
| Zdroj: | European Journal of Pharmacology. 860:172529 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/j.ejphar.2019.172529 |
| Popis: | Parasympathetic regulation of urinary bladder contractions primarily involves acetylcholine release and activation of detrusor smooth muscle (DSM) muscarinic acetylcholine (mACh) receptors. Co-release of ATP and activation of DSM purinergic P2X1-receptors may participate as well in some species. Both types of neuromuscular transmission (NMT) are impaired in diabetes, however, which factors may contribute to such impairment remains poorly understood. Here by using rats with streptozotocin(STZ)-induced type I diabetes (8th week after induction) we show that contribution of atropine-sensitive m-cholinergic component to the contractions of urothelium-denuded DSM strips evoked by electric field stimulation (EFS) greatly increased when diabetic bladders presented overt signs of accompanying cystitis. Modeling of hemorrhagic cystitis alone in control rats by cyclophosphamide injection only modestly increased m-cholinergic component of EFS-contractions. However, exposure of DSM strips from control animals to acetylcholinesterase (AChE) inhibitor, neostigmine (1–10 μM) largely reproduced alterations in EFS contractions observed in diabetic DSM complicated by cystitis. Ellman's assay revealed statistically significant 31% decrease of AChE activities in diabetic vs. control DSM. Changes in purinergic contractility of diabetic DSM were consistent with altered P2X1-receptor desensitization and re-sensitization. They could be mimicked by pharmacological inhibition of ATP-degrading ecto-ATPases with ARL 67156 (50 μM), pointing to compromised extracellular ATP clearance as underlying reason. We conclude that decreased AChE activities associated with diabetes and likely cystitis provide complementary factor to the described in literature altered expression of mACh receptor subtypes linked to diabetes as well as to cystitis to produce dramatic modification of cholinergic NMT. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect