Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.7 (acetylcholinesterase)
 28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Phasic contractile responses of the intact rat urinary bladder to the muscarinic agonists carbachol and pilocarpine became nearly blocked as the concentrations were progressively increased to 200-500 microM. In contrast, tonic contractile responses remained elevated throughout progressive increases in agonist concentration. 2. Nerve-induced phasic contractions to 1 Hz stimuli were potentiated throughout progressive increases in the concentration of muscarinic agonists. However, these responses were more atropine sensitive than untreated controls and responses to 1 Hz stimuli were nearly abolished. 3. After inhibition of cholinesterase, the action of cholinergic transmitter released during prolonged nerve stimulation may extend to the tonic contractile state of the bladder and potentiate responses to 1H stimuli. Nerve-induced responses were more atropine sensitive than untreated controls. 4. Bladder tone was increased and nerve-induced contractions to 1-Hz stimuli were also potentiated in an elevated K+ environment. However, atropine sensitivity of nerve-induced responses w s reduced. 5. Nerve-induced bladder contractions were linked to the tonic contractile state of the bladder muscle, controlled physiologically by muscarinic receptors. Since phasic contractile responses to muscarinic agonists were abolished at high concentrations by receptor desensitization, nerve-induced responses must be elicited under these conditions by a non-cholinergic transmitter.
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PMID:Atropine-resistant transmission in partially depolarized rat urinary bladder. 216 51

Two groups of patients who developed denervation of the bladder after excision of the rectum for carcinoma have been studied by histological examination of bladder biopsies. The groups were compared with a group of control patients of a similar age. One group with denervation of the bladder was studied soon after (7 weeks) and the other group in the long term (10 months) after operation. Bladder biopsies were stained for acetylcholinesterase, catecholamines and connective tissue. Tissue was also processed for electron microscopy. In control patients, the ratio of cholinesterase positive nerves to the number of smooth muscle nuclei (24:100) was significantly greater than in patients with denervation of the bladder studied soon after operation (2.5: 100; P less than 0.01). Appearances consistent with degenerate nerve terminals were observed on electron microscopy in these patients. No increase in the density of adrenergic nerves was observed in either group of patients with denervation of the bladder. In the long term, a greater density of cholinergic innervation was noted compared with patients studied soon after operation (P less than 0.05). In addition, nerve terminals, similar in appearance to those of control patients, were observed on electron microscopy. The findings in patients with denervation of the bladder studied in the long term after operation are consistent with partial regeneration of autonomic nerves. They suggest that, whilst histological examination of bladder biopsies may be useful soon after excision of the rectum, they may be less sensitive in the long term.
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PMID:Histological appearances of the nerves of the bladder in patients with denervation of the bladder after excision of the rectum. 715 Sep 19

A pharmacological analysis was carried out in the rat urinary bladder to assess the nature of muscarinic receptors subtypes functionally involved in the negative feedback mechanism regulating acetylcholine (ACh) secretion from postganglionic cholinergic nerve terminals and in smooth muscle contraction. Bladder strips were preincubated with 3H-choline, and the electrically evoked [3H]ACh release was detected simultaneously with contraction in the absence of acetylcholinesterase inhibitors. The effects were compared of seven muscarinic antagonists on [3H]ACh secretion (prejunctional effect) and muscle contraction (postjunctional effect). The rank order of postjunctional potencies (-log EC50) for the seven antagonists (atropine > 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) > hexahydrosiladiphenidol hydrochloride (HHSiD) > tripitramine > pirenzepine > AF DX-116 > methoctramine) as well as their postjunctional affinity estimates (pA2) are in keeping with the notion that muscarinic receptors responsible for bladder contraction belong to the M3 subtype. The M3 subtype-preferring 4-DAMP and HHSiD did not discriminate between prejunctional and postjunctional effects. The M2/M4 subtype-preferring antagonists tripitramine, methoctramine and AF-DX 116 were more potent in facilitating the evoked [3H]ACh release than in inhibiting the contractile response. The rank order of prejunctional potencies was atropine > 4-DAMP > tripitramine > HHSiD > methoctramine > AF-DX 116 > pirenzepine, indicating the involvement of M4 receptors. Furthermore, when potency relationship was determined by correlating prejunctional-log EC50 values with published constants for cloned and natives muscarinic receptor subtypes, the correlations were significant for both M4 and M5 subtypes, but the best correlation found (P < .001) was for the M4 subtype. These findings suggest that the negative feedback mechanism inhibiting the release of ACh in the rat urinary bladder is mediated by prejunctional autoreceptors of the M4 subtype.
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PMID:M4 muscarinic autoreceptor-mediated inhibition of -3H-acetylcholine release in the rat isolated urinary bladder. 935 95

Posterior urethral valves (PUV) are the most common cause of bladder outlet obstruction (BOO) in infancy. Bladder instability, poor compliance and myogenic failure are responsible for the poor long-term prognosis in these patients. Previous studies have reported abundance of sensory neuropeptides, e.g. substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and acetylcholinesterase (AchE) nerves in the urinary bladder. We hypothesized that the functional changes in the bladder following BOO are due to alteration in cholinergic and sensory neuropeptide innervation. We therefore investigated cholinergic and sensory innervation of urinary bladder following BOO. Fifteen immature male guinea pigs (Hartley strain) 3-4 weeks old and weighing approximately 250 g. underwent placement of a silk ligature around the bladder neck to induce BOO. Controls included 5 sham-operated animals. The animals were killed 1, 2 and 4 weeks following obstruction, respectively. Whole-mount preparation and conventional sections of bladder wall were performed. AchE histochemistry, and single-label immunofluorescence histochemistry for SP, CGRP and VIP were utilized. Light microscopy and laser scanning confocal microscopy were used to assess the results. AchE staining showed marked increase in cholinergic innervation density within the suburothelial region following BOO. The staining for SP, CGRP and VIP demonstrated marked reduction in sensory nerve density within the suburothelial region 1 week following BOO and the lack of sensory innervation 4 weeks after BOO. The marked reduction in sensory innervation of the bladder and simultaneous increase in cholinergic innervation following BOO may lead to bladder instability and decrease in bladder compliance.
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PMID:Alterations in cholinergic and neuropeptide innervation of urinary bladder following partial bladder outlet obstruction. 1275 93

Underactive bladder (UAB) or detrusor underactivity (DU) is a common yet still poorly understood urological problem. In addition to true detrusor failure and neuropathy, the inhibitory effects of detrusor contraction by the striated urethral sphincter and the bladder neck through alpha-adrenergic activity may also play a role in the development of UAB or DU. Treatment of UAB or DU aims to reduce the postvoid residual (PVR) urine volume and increase voiding efficiency, either by spontaneous voiding or abdominal straining. Pharmacotherapy with parasympathomimetics or cholinesterase inhibitors might be tried, and benefits can be achieved in combination with alpha-blockers. Bladder outlet surgeries, including urethral onabotulinumtoxinA injection, transurethral incision of the bladder neck, and transurethral incision or resection of the prostate can effectively improve voiding efficiency and decrease the PVR in most patients with DU. The mechanisms have not been well elucidated. It is likely that ablation of the bladder neck or prostatic urethra might not only decrease bladder outlet resistance but also abolish the sympathetic hyperactivity which inhibits detrusor contractility in patients with idiopathic UAB or DU.
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PMID:Current pharmacological and surgical treatment of underactive bladder. 2929 45