Impairment of cholinergic bladder contractility in rat model of type I diabetes complicated by cystitis: Contribution of neurotransmitter-degrading ectoenzymes.

08:00 EDT 9th July 2019 | BioPortfolio

Summary of "Impairment of cholinergic bladder contractility in rat model of type I diabetes complicated by cystitis: Contribution of neurotransmitter-degrading ectoenzymes."

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.


Journal Details

This article was published in the following journal.

Name: European journal of pharmacology
ISSN: 1879-0712
Pages: 172529


DeepDyve research library

PubMed Articles [21469 Associated PubMed Articles listed on BioPortfolio]

Detrusor contractility to parasympathetic mediators is differentially altered in the compensated and decompensated states of diabetic bladder dysfunction.

Diabetic bladder dysfunction (DBD) affects up to 50% of all diabetic patients, characterized by symptoms of both overactive and underactive bladder. While most diabetic bladder dysfunction studies wer...

Do functional changes occur in the bladder due to bladder outlet obstruction? - ICI-RS 2018.

Studies on bladder dysfunction (BD), more specifically functional-urodynamic changes in the bladder as a result of bladder outlet obstruction (BOO) have been summarized for this TT. Based on available...

A Feasibility Study of Paired Continuous Glucose Monitoring Intrapartum and in the Newborn in Pregnancies Complicated by Type 1 Diabetes.

To describe the continuous glucose monitoring (CGM) profiles of type 1 diabetes (T1D) offspring in the early neonatal period and its association with maternal intrapartum glucose control.

Smooth muscle-specific deletion of MnSOD exacerbates diabetes-induced bladder dysfunction in mice.

Bladder dysfunction in diabetes progresses gradually over time. However, the mechanisms of the development are not clear. We test the hypothesis that oxidative stress plays a key role in the developme...

Electroacupuncture in rats normalizes the diabetes-induced alterations in the septo-hippocampal cholinergic system.

Diabetes induces early sufferance in the cholinergic septo-hippocampal system, characterized by deficits in learning and memory, reduced hippocampal plasticity and abnormal pro-nerve growth factor (pr...

Clinical Trials [13233 Associated Clinical Trials listed on BioPortfolio]

The Long Term Effects of Alfuzosin(Xatral XL) in LUTS/BPH Patients: Evaluation of Voiding and Storage Function

Benign prostatic hyperplasia (BPH) is a common condition among older men. The efficacy of α1-blockers for treating BPH has been well documented and they are recommended for the treatment ...

Genomics and Epigenomics for New Insights in fEmale OAB (GENIE) Study

Millions of women suffer from overactive bladder, and the changes in bladder function affect their quality of life. The study team believes that it needs to be better understand why women ...

A Phase 3, Randomized, Double-blind, Parallel-group, Comparative Study and a Phase 3, Multicenter, Open-label, Long-term Study of SYR-472 (25 mg) in Patients With Type 2 Diabetes Mellitus Complicated by Severe Renal Impairment or End-stage Renal Failure

The purpose of this study is to evaluate the efficacy and safety of SYR-472 when administered at a dose of 25 mg once weekly using placebo as a control in patients with type 2 diabetes mel...

Lifestyle Intervention in Obesity, Effect on Diabetes

There are evidence from numerous studies on effect of lifestyle intervention in morbidly obese patients with type 2 diabetes. This study examines the effect of the "Evje-model" on type 2 d...

A Study of the Pharmacokinetics/Pharmacodynamics of GK Activator (2) in Type 2 Diabetes Patients With Hepatic Impairment.

This study will investigate the effect of hepatic impairment on the pharmacokinetics, pharmacodynamics, safety and tolerability of GK Activator (2) in type 2 diabetes patients with mild an...

Medical and Biotech [MESH] Definitions

The time period before the development of symptomatic diabetes. For example, certain risk factors can be observed in subjects who subsequently develop INSULIN RESISTANCE as in type 2 diabetes (DIABETES MELLITUS, TYPE 2).

A subclass of DIABETES MELLITUS that is not INSULIN-responsive or dependent (NIDDM). It is characterized initially by INSULIN RESISTANCE and HYPERINSULINEMIA; and eventually by GLUCOSE INTOLERANCE; HYPERGLYCEMIA; and overt diabetes. Type II diabetes mellitus is no longer considered a disease exclusively found in adults. Patients seldom develop KETOSIS but often exhibit OBESITY.

A strain of Rattus norvegicus which is a model for spontaneous insulin-dependent diabetes mellitus (DIABETES MELLITUS, INSULIN-DEPENDENT).

Drugs that bind to but do not activate CHOLINERGIC RECEPTORS, thereby blocking the actions of ACETYLCHOLINE or cholinergic agonists.

Drugs that inhibit cholinesterases. The neurotransmitter ACETYLCHOLINE is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system.

Quick Search


DeepDyve research library

Relevant Topics

Bladder Cancer
Non-invasive bladder cancer is a cancer that is only in the inner lining of the bladder. Invasive bladder cancer is cancer that has spread into the deeper walls of the bladder. When the cancer has spread outside the bladder to other parts of the body, th...

Nephrology - kidney function
Nephrology is a specialty of medicine and pediatrics that concerns itself with the study of normal kidney function, kidney problems, the treatment of kidney problems and renal replacement therapy (dialysis and kidney transplantation). Systemic conditions...

Searches Linking to this Article