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PubMed2006

Noninvasive squamous lesions in the urinary bladder: a clinicopathologic analysis of 29 cases.

Noninvasive squamous lesions are distinctively uncommon in biopsies of the urinary bladder with the exception of nonkeratinizing squamous metaplasia. The clinical significance of these squamous lesions in the bladder remains to be explored. A total of 29 cases of transurethral biopsies and resections of the bladder containing noninvasive squamous lesions (excluding nonkeratinizing metaplasia) were studied from the consult files of one of the authors. These cases included keratinizing squamous metaplasia (5), verrucous squamous hyperplasia (5), squamous papilloma (5), condyloma acuminatum (3), and squamous cell carcinoma in situ (CIS) (11). Immunohistochemistry for epithelial growth factor receptor (EGFR) and in situ hybridization for wide-range human papillomavirus was performed on 23 cases. The follow-up period ranged from 2 months to 3 years with an average of 1.5 years. After the initial diagnoses in biopsies of the bladder, 10 patients received cystectomies, and 7 patients received repeat tissue sampling of the bladder. Of the 5 patients with keratinizing squamous metaplasia, 2 patients had invasive urothelial carcinoma with squamous features in their cystectomy specimens at intervals of 3 and 14 months, respectively, 1 had persistent keratinizing squamous metaplasia on rebiopsy. Of the 5 patients with verrucous squamous hyperplasia, 1 patient had invasive squamous cell carcinoma at cystectomy at an interval of 14 months, 1 had squamous cell CIS on rebiopsy, 1 had persistent verrucous squamous hyperplasia on rebiopsy, and 2 had no evidence of disease at 6 and 24 months. Of the 5 patients with squamous papilloma, 1 patient had low-grade urothelial carcinoma at cystectomy at an interval of 21 months (h/o low-grade urothelial carcinoma preceding papilloma diagnosis), 2 were free of lesions at rebiopsy. Of the 3 patients with condyloma acuminatum, 1 had squamous CIS at cystectomy at an interval of 3 months, 1 had invasive squamous cell carcinoma at 20 months. Of the 11 patients with squamous cell carcinoma in situ (CIS), 3 patients had invasive squamous cell carcinoma at intervals of 2, 3, and 4 months, respectively, 1 had invasive urothelial carcinoma with squamous features in cystectomies at an interval of 12 months, 1 had squamous cell CIS at 10 months, 1 had high-grade urothelial carcinoma (not otherwise specified) at rebiopsy at an interval of 6 months, and 1 had no evidence of disease at 8 months. Among the 9 patients with invasive carcinoma, 4 patients died in the period of 0.5 to 3 years after the diagnoses. Immunohistochemical study with EGFR demonstrated strong signals in 20 cases and no signals in 2 cases. Wide-range human papillomavirus DNA signal was detected in 1 case of condyloma acuminatum and 1 case of squamous cell CIS. Keratinizing squamous metaplasia, verrucous squamous hyperplasia, and condyloma acuminatum in the urinary bladder can be associated with subsequent or concurrent in situ, or invasive squamous carcinoma and should be closely followed. Squamous cell CIS in the urinary bladder is often associated with subsequent or concurrent invasive carcinoma with squamous differentiation. Enhanced expression of EGFR in these bladder squamous lesions suggests that EGFR may represent a logic therapeutic target in those squamous lesions that are difficult to manage clinically.

Adult↗
PubMed1999

Chromosomal imbalances in small cell carcinomas of the urinary bladder.

Small cell carcinomas (SCCs) represent a rare histological subtype of urinary bladder cancer. Little is known abut the genetic alterations in these tumours. To identify chromosomal aberrations that are typically present in SCC of the urinary bladder, ten tumours were analysed by comparative genomic hybridization (CGH). CGH allows screening for all relative DNA copy number gains and losses present in a tumour. SCCs of the bladder were characterized by a high number of genomic alterations (mean: 11.3 per tumour). Deletions were most frequent at 10q (7 of 10 tumours deleted), 4q, 5q (5/10 each), and 13q (4/10). These regions may carry tumour suppressor genes with relevance for this particular tumour type. Gains of DNA sequences were most prevalent at 8q (5/10), 5p, 6p, and 20q (4/10 each). High level amplifications were found at 1p22-32, 3q26.3, 8q24, and 12q14-21. These loci may pinpoint the localization of oncogenes with relevance for small cell bladder cancer. The analysis of one tumour having areas of both SCC and transitional cell carcinoma strongly suggests that SCC can develop from TCC through the acquisition of additional genetic alterations.

Carcinoma, Small Cell↗
PubMed1983

The effects of naloxone on the neural control of the urinary bladder of the cat.

Naloxone in doses ranging from 0.5 to 512 micrograms/kg i.v., enhanced reflex contractions of the urinary bladder of the cat. At the lowest doses (threshold, 0.5-5 micrograms/kg) the drug increased the frequency of spontaneous bladder contractions. In large doses (10-100 micrograms/kg) the drug produced an initial tonic contraction of bladder lasting 15-40 min followed by a period of high frequency rhythmic activity. Multiunit firing in parasympathetic postganglionic nerves on the surface of the urinary bladder was also enhanced. Bursts of firing which in untreated animals occurred during large bladder contractions occurred continuously during the entire sustained contraction of the bladder following large doses of naloxone. Various evidence indicates that the site of action of naloxone is in the central nervous system. These findings suggest that the parasympathetic reflex pathway to the urinary bladder may be subject to tonic enkephalinergic inhibitory control.

Animals↗
PubMed1988

Effects of trisodium nitrilotriacetate monohydrate, nitrilotriacetic acid and ammonium chloride on urinary bladder carcinogenesis in rats pretreated with N-bis(2-hydroxypropyl) nitrosamine.

The effects of trisodium nitrilotriacetate monohydrate (Na3 NTA.H2O) nitrilotriacetic acid (H3NTA) and ammonium chloride (NH4Cl) on two-stage urinary bladder carcinogenesis were examined. Carcinogenesis was initiated by administration of 0.2% N-bis (2-hydroxypropyl)-nitrosamine (DHPN) to male Wistar rats in the drinking water for 2 weeks, and then the animals were treated with basal diet containing Na3NTA.H2O, Na3NTA.H2O plus NH4Cl, H3NTA, H3NTA plus NH4Cl, or without these chemicals for 28 weeks. Na3NTA.H2O increased significantly the resultant incidence of neoplastic and preneoplastic lesions of the urinary bladder. Moreover, treatment with Na3NTA.H2O, without the initiation, itself induced papillary or nodular (PN)-hyperplasia. H3NTA produced only a slight increase in the incidence of preneoplastic urinary bladder lesions (PN-hyperplasia) in rats initiated by DHPN, and this was not statistically significant. Elevation of both pH and sodium ion concentration in the urine were correlated with promotion of tumor development. These data showed that Na3NTA.H2O was more effective than H3NTA with regard to promoting potential, and that changes in both urinary pH and concentration of sodium played important roles in enhancement of urinary bladder tumorigenesis by these chemicals.

Acetates↗
PubMed1995

Significance of epidermal growth factor receptor and c-erbB-2 protein expression in transitional cell cancer of the upper urinary tract for tumour recurrence at the urinary bladder.

An immunohistochemical study of the expression of epidermal growth factor receptor (EGFR) and c-erbB-2 protein was performed in fresh-frozen sections from 30 patients with transitional cell cancers (TCCs) of the upper urinary tract (15 renal pelvic cancers, 15 ureteral cancers) who underwent total nephroureterectomy. We followed them and examined whether TCC appeared in the urinary bladder. The follow-up period ranged from 116 to 2348 days (mean 666 days). The mean period until a secondary urinary bladder cancer appeared was 306 days (116-829 days). Thirteen of those 30 TCCs (43.3%) showed increased expression of EGFR, and 11 TCCs (36.7%) showed increased expression of c-erbB-2. In 12 of 30 patients (40.0%), a secondary urinary bladder cancer appeared after surgery. In only one of the ten patients (10.0%) whose tumours did not exhibit increased expression of either of these receptors the tumour recurred in bladder. On the other hand, in 11 of 20 (55.0%) patients whose tumours had increased EGFR and/or c-erbB-2 expression, secondary urinary bladder cancers recurred after surgery (P < 0.05). Thus, the recurrence rate of TCCs with increased EGFR and/or c-erbB-2 expression was significantly higher than that of tumours showing no increased expression of these receptors (P < 0.01). These results suggest that the immunohistochemical detection of the expression of EGFR and c-erbB-2 in urothelial cancers of the upper urinary tract might be a useful method for determining the likelihood of secondary bladder cancer recurrences.

Aged↗
PubMed1988

[Experimental model of urinary bladder tumor in rats for evaluation of chemotherapeutic agents].

The chemotherapeutic agents were evaluated using the experimental urinary bladder tumor rat model induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN). Nine hundred and fourteen male rats received 0.05% BBN in drinking water for 8 weeks, and were divided into 35 groups to follow the regimens of chemotherapeutic agents. Thirty one groups received the agents after BBN treatment, and 4 groups were given the oral agents starting simultaneously with BBN treatment. All rats were killed at 20 weeks and incidence of the urinary bladder was examined histopathologically. The following 13 agents were evaluated; adriamycin (ADM), mitomycin-C (MMC), cyclophosphamide (CPM), 5-fluoro-uracil (5-Fu), N-(2-tetrahydrofuryl)-5-fluorouracil (FT-207), neocarcinostatine (NCS), carbazil quinone (CQ), bleomycin (BLM), vincristine (VCR) and cis-diammine-dichloroplatinum (CDDP) were dosed intraperitoneally, and N-(2-tetrahydrofuryl)-5-fluorouracil (FT-207), 1: 4 mixture of FT-207 and uracil (UFT) and 1-Hexylcarbamoyl-5-fluorouracil (HCFU) were dosed orally. Among these agents, 5-Fu, FT-207, CQ, VCR, CDDP, UFT and HCFU were effective in inhibiting the incidence of urinary bladder tumor induced by BBN. In conclusion, the experimental bladder tumor rat model induced by BBN seems to be useful in evaluating the effective chemotherapeutic agents for a superficial bladder cancer. The importance of the experimental animal model for the evaluation of chemotherapeutic agents is discussed.

Animals↗
PubMed2001

[Small cell carcinoma of the urinary bladder with synchronous esophageal cancer and incidental lung cancer: a case report].

We present a case of triple primary cancers occurring synchronously in the urinary bladder, esophagus, and incidentally in the lung. A 65-year-old man with a chief complaint of gross hematuria was admitted to our hospital. Cystoscopy, computed tomography (CT) and magnetic resonance imaging (MRI) revealed a non-papillary broad-based bladder tumor. Histological diagnosis was transitional cell carcinoma of the urinary bladder and he underwent one course of neoadjuvant chemotherapy (M-VAC) with the preoperative diagnosis of T3bN0M0. After one course of chemotherapy, chest CT, lymph node biopsy and esophagoscopy revealed squamous cell carcinoma of the esophagus. He first underwent radiochemotherapy (total 70 Gy, CDDP 5 mg x 41, 5-FU 250 mg x 24) for esophageal cancer and achieved complete remission. Then, he underwent radiotherapy for a total of 60 Gy for bladder cancer. However, his general condition gradually became worse and he died from metastatic cancer. The autopsy proved that he died from multiple metastases of small cell carcinoma of the urinary bladder and incidentally squamous cell carcinoma of the lung was identified.

Aged↗
PubMed2006

Laparoscopic intraperitoneal repair of high-up urinary bladder fistula: a review of 12 cases.

Conventional abdominal operations for urinary bladder fistula have limitations like increased morbidity, more hemorrhage, more postoperative pain, and longer hospital stay. Laparoscopic repair of bladder fistula was done to explore the potential role of laparoscopic surgery in this field. Twelve women with vesicovaginal (11) and vesicouterine (one) fistula, of both gynecological (seven) and obstetric (five) origins, were treated by laparoscopic intraperitoneal repair between 1991 and 2004. The bladder wall was mobilized and repaired by interrupted stitches in single-layer followed by omental interposition. All cases were completed laparoscopically without any significant intra- or postoperative complication. Gynecological cases were discharged on the fourth day. Urinary catheters of all women were removed on the 14th day, and all but one obstetric fistula (91% success) were closed. Long-term follow-up confirmed the cure. Laparoscopic repair is an excellent method of repairing urinary bladder fistula located near the vaginal apex.

Female↗
PubMed2006

[Paraganglioma of the urinary bladder: a case report].

A patient with paraganglioma of the urinary bladder is reported. A 65-year-old woman was referred to our hospital with the chief complaint of postvoiding headache, palpitation, and cold sweat. She had has no episodes of hematuria. On laboratory data, mild elevation was found in plasma neuron specific enolase (NSE), urinary noradrenaline and urinary metanephrine. The patient showed hypertension after urination with the elevation of plasma noradrenaline. 131I-MIBG scintigraphy showed abnormal accumulation in the bladder, and no abnormal accumulation in the other lesion. Pelvic magnetic resonance imaging (MRI) revealed a solid tumor of the urinary bladder, measuring 2 cm in diameter. Paraganglioma of the urinary bladder was diagnosed and the tumor was extirpated. The tumor measured 2 x 2 x 1.5 cm, and histopathologically diagnosed as paraganglioma. After extirpation, the patient became free of the postvoiding symptoms, and showed normal catecholamine levels. She has been followed up for 4 months after operation without any evidence of recurrence.

Aged↗
PubMed1992

Changes in muscarinic responsiveness, muscarinic receptor density and Ca2+ mobilization of the urinary bladder in streptozotocin-induced diabetic rats.

Functional changes in the urinary bladder obtained from diabetic rats were investigated by determining the responsiveness to acetylcholine (ACh). Maximal contraction of the detrusor strips in response to ACh was significantly enhanced in the diabetic rats. Ca(2+)-induced contracture of the detrusor strips, which had been incubated with 10(-3) M ACh in the presence of nicardipine in Ca(2+)-free medium, was significantly augmented in diabetic rats. Ca(2+)-contracture in Ca(2+)-free, isotonic high-K+ (60 mM) medium was not changed in diabetic state. The density of muscarinic receptors to 3H-QNB was significantly higher in the bladder from diabetic rats compared to age-matched control rats. These results suggest that tone of the autonomic nervous system in the bladder may be decreased in diabetes and, thus, compensatory increase in density of muscarinic receptors may occur. Furthermore, an increased contractile response of the detrusor strips of the urinary bladder to ACh in diabetic rats also may be due to an increased influx of extracellular Ca2+ through the receptor-operated Ca2+ channels but not the voltage-dependent Ca2+ channels.

Acetylcholine↗
PubMed2002

Transitional cell carcinomas of the urinary bladder. A histopathological study.

OBJECTIVE: To determine the histological grading and muscle invasion in Transitional Cell Carcinomas of the Urinary Bladder; and to evaluate whether any correlation exists between tumour grade and muscle invasion. METHOD: A Retrospective study of all consecutive cases of Transitional Cell Carcinomas of the Urinary Bladder diagnosed at Aga Khan University Hospital between 1st Jan 1997 and 31st Dec 2000. RESULTS: This study included 495 cases of Transitional Cell Carcinoma of the Urinary Bladder. M: F ratio was 4:1. Ages of patients ranged from 30 years to 87 years. Mean age in males was 59.1 years and in females 58.8 years. Forty four percent cases were Grade II, and 29.5% Grade III. None of the Grade I lesions were invasive, 10% Grade II tumours, 61.41% of Grade III and all Grade IV tumours were invasive. CONCLUSION: There is a definite correlation between advancing tumour grade and muscle invasion.

Adult↗
PubMed1999

Dose-dependent binding of ortho-phenylphenol to protein but not DNA in the urinary bladder of male F344 rats.

ortho-Phenylphenol (OPP) is a widely used fungicide and antibacterial agent that is also known to be highly effective in inducing bladder tumors in male F344 rats. At present, neither the role of the urinary bladder in the bioactivation of OPP metabolites nor the nature of the molecular target is understood. To address these issues, we investigated the relationship between OPP dosage and macromolecular adduct formation in the urinary bladder of male F344 rats. Male F344 rats were treated with 0, 15, 50, 125, 250, 500, 1000 mg/kg of OPP and its radiocarbon analogue via oral gavage. The dosed rats were euthanized after 24 h, and the proteins were extracted from the liver, kidney, and bladder. The amount of radioactivity associated with the extracted protein was quantified using highly sensitive accelerator mass spectrometry. Protein binding in liver and kidney exhibited a linear or modest curvilinear relationship over the dose range studied. In the urinary bladder, however, a pronounced nonlinear relationship between protein adduct levels and administered dose was observed. The measured protein adduct levels were in agreement with the predicted concentrations of phenylbenzoquinone based on a proposed mechanism involving free phenylhydroquinone autoxidation in the urine. Unlike protein binding, DNA adducts measured from the same bladder samples did not show a significant difference from the control group. These data are consistent with the hypothesis that OPP is an indirect acting carcinogen, and that regenerative hyperplasia due to OPP-metabolite cytotoxicity and/or binding of OPP metabolites to protein targets may play an important role in OPP-induced bladder carcinogenesis.

Animals↗
PubMedDate not supplied

[Urodynamics of upper urinary tracts after intestinal plastic surgery on urinary bladder (experimental study)].

In dog experiments, the urinary bladder was replaced for an isolated intestinal segment to test upper urinary tract function as regards configuration of the established urine reservoir early and late after the surgery. Intestinal plastic surgery of the bladder changes parameters of ureteral function in unchanged potential reserve of ureteral contraction. Postileocystoplasty urodynamics of the upper urinary tracts is characterized by lowering of intraureteral pressure, decreased amplitude of ureteral contractions, enhanced tonicity and motility. Plastic replacement of the bladder with isolated intestinal segment is not contraindicated in the solitary kidney.

Animals↗
PubMed2006

Effect of storage upon material properties of lyophilized porcine extracellular matrix derived from the urinary bladder.

Xenogeneic extracellular matrices (ECMs) have been developed as off-the-shelf biologic scaffolds that have been effectively used in preclinical and clinical applications for tissue reconstruction. Such materials must be suitable for terminal sterilization and capable of storage for extended periods of time without significant changes in material properties and bioactivity. Material properties of interest for ECM scaffolds include hydrostatic permeability index (PI), uniaxial maximum load and elongation, maximum tangential stiffness (MTS), suture retention strength (SRS), and ball-burst strength (BBS). The present study evaluated these material properties for lyophilized forms of an ECM scaffold derived from the porcine urinary bladder, termed urinary bladder matrix (UBM), that was terminally sterilized by e-beam irradiation at 22 kGy and stored at room temperature (RT; 20-24 degrees C) or refrigerated temperature (REFT; 4-8 degrees C) for up to 12 months. UBM devices showed no change in SRS, BBS, and hydrostatic PI after the evaluation period. Lyophilized devices stored at RT showed an increase in maximum load and MTS while devices stored at REFT showed an increase in maximum elongation after 1 year of storage (p < 0.05). These results indicate that structural changes in the UBM device may slowly occur as a function of prolonged storage and storage temperature.

Animals↗
PubMed1999

Urinary bladder lesions after the Chernobyl accident: immunohistochemical assessment of p53, proliferating cell nuclear antigen, cyclin D1 and p21WAF1/Cip1.

During the 11-year period subsequent to the Chernobyl accident, the incidence of urinary bladder cancer in Ukraine has increased from 26.2 to 36.1 per 100,000 population. Cesium-137 (137Cs) accounts for 80-90% of the incorporated radioactivity in this population, which has been exposed to long-term, low-dose ionizing radiation, and 80% of the more labile pool of cesium is excreted via the urine. The present study was performed to evaluate the histopathological features and the immunohistochemical status of p53, p21WAF1/Cip1, cyclin D1 and PCNA (proliferating cell nuclear antigen) in urinary bladder mucosa of 55 males (49-92 years old) with benign prostatic hyperplasia who underwent surgery in Kiev, Ukraine, in 1995 and 1996. Group I (28 patients) inhabiting radiocontaminated areas of the country, group II (17 patients) from Kiev city with less radiocontamination and a control group III (10 patients) living in so-called "clean" areas of Ukraine were compared. In groups I and II, an increase in multiple areas of moderate or severe dysplasia or carcinoma in situ was seen in 42 (93%) of 45 cases. In addition, two small transitional cell carcinomas were found in one patient in each of groups I and II. Nuclear accumulation of p53, PCNA, cyclin D1, and to a lesser extent p21WAF1/Cip1, was significantly increased in both groups I and II as compared with the control group III, indicating possible transformation events or enhancement of repair activities, that may precede the defect in the regulatory pathway itself, at least in the G1 phase of the cell cycle. Our results suggest that early malignant transformation is taking place in the bladder urothelium of people in the radiocontaminated areas of Ukraine and that this could possibly lead sometime in the future to an increased incidence of urinary bladder cancer.

Aged↗
PubMedDate not supplied

Intraarterial infusion of cisplatin with and without preoperative concurrent radiation for urinary bladder cancer: a preliminary report.

We evaluated the clinical efficacy of treating urinary bladder cancer by intraarterial infusion of cisplatin using an implanted reservoir with and without preoperative concurrent radiation. No previous reports have compared the results obtained by these two methods of treatment. Twenty-three patients with bladder cancer were treated by intraarterial infusion of cisplatin using an implanted reservoir with (n = 13) and without (n = 10) concurrent radiation. The cisplatin plus radiation group received intraarterial cisplatin at a total dose of 200-400 mg and concurrent radiation to a total dose to 30 Gy. The cisplatin group received intraarterial cisplatin at a total dose of 100-600 mg. In the cisplatin plus radiation group, the overall tumor response rate was 92%. Seven of 13 (53%) patients obtained complete response (CR), and the 2-year actuarial survival rate was 92%. Only one of the seven complete responders has had a local recurrence. In the cisplatin group, the overall tumor response rate was 90%. Four of 10 (40%) patients obtained CR, and median survival was 8 months. Three of the four complete responders have had local recurrence. There was no significant difference between these two groups in the frequency of side effects. Concurrent radiation therapy with intraarterial cisplatin resulted in a very low rate of recurrence of bladder cancer compared with intraarterial cisplatin therapy alone. This method was useful for urinary bladder cancer and may become the treatment of choice for this type of cancer.

Aged↗
PubMed1989

Development and validation of a new assay for O6-alkylguanine-DNA-alkyltransferase based on the use of an oligonucleotide substrate, and its application to the measurement of DNA repair activity in extracts of biopsy samples of human urinary bladder mucosa.

A simplified and highly sensitive assay for the determination of O6-alkylguanine-DNA-alkyltransferase has been developed and validated by the analysis of extracts of human urinary bladder mucosa. The new assay involves the use of a synthetic dodecanucleotide containing a single O6-methylguanine residue as substrate for the enzyme. This substrate is 5'-end-labelled with [35S]PO3 and separation of repaired and unrepaired oligonucleotide is achived by immuno-precipitation with polyclonal antibodies specific for O6-methyldeoxyguanosine. Kinetic analysis of the repair of the oligonucleotide by extracts of Escherichia coli and rat liver showed that the reaction is first-order in substrate and enzyme and gave the molecular rate constants 7.5 x 10(6) mol-1 1-1 sec-1 and 8.0 x 10(6) mol-1 1-1 sec-1, respectively. The rate constants for the repair of the corresponding O6-ethylguanine-containing oligonucleotide were 3.0 x 10(5) mol-1 l-1 sec-1 and 3.6 x 10(6) mol-1 l-1 sec-1, respectively. Analysis of extracts of 48 samples of normal or neoplastic human urinary bladder mucosa obtained by transurethral biopsy or at surgery, by the new method or by a method involving use of [3H]-methylated DNA as substrate and HPLC, indicated excellent agreement between the two methods. The mean AGT content of normal urinary bladder mucosa obtained from individuals without diagnosed bladder cancer was 0.181 +/- 0.081 (mean +/- SD) fmol/microgram protein, that of neoplastic samples 0.323 +/- 0.177 fmol/microgram protein and that of normal tissue obtained from patients with bladder cancer 0.183 +/- 0.068 fmol/microgram protein. The new method is convenient, rapid and extremely sensitive (it can readily measure femtomole quantities of enzyme) and should prove useful for studies of the biochemical epidemiology of DNA repair.

Animals↗
PubMed1985

Dietary choline affects response to acetylcholine by isolated urinary bladder.

Age-related increases occur in the response of isolated urinary bladders to the parasympathetic neurotransmitter acetylcholine (ACh). Experiments were carried out to determine whether long-term elevation or diminution in the amount of ingested choline can also affect the response of the urinary bladder to ACh. Female C57BL/6J mice were maintained on a choline-deficient chow and on drinking water supplemented with either 0, 1.5, or 4.0 mg/ml choline chloride from 8 to 20 months of age. Isolated bladders from choline deficient animals showed a 46% increase in the maximum response to ACh as compared to those from normal choline animals, while bladders from animals on choline enriched diets showed a 15% decrease in maximum contractile response. Radioligand binding experiments suggested that the functional changes result from alterations in the density of muscarinic receptors in the bladder. The results are consistent with the hypothesis that muscarinic receptors are down-regulated to compensate for increased parasympathetic activity associated with choline-enriched diets and up-regulated to compensate for decreased parasympathetic activity associated with choline-deficient diets.

Acetylcholine↗