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PubMed2002

Increased expression of gallbladder cholecystokinin: a receptor in prairie dogs fed a high-cholesterol diet and its dissociation with decreased contractility in response to cholecystokinin.

A series of our studies have shown that formation of cholesterol-supersaturated bile in patients with cholesterol gallstone disease is causatively related to decreased gallbladder contractility and mucin hypersecretion by the gallbladder. Supersaturated bile may modify the composition of gallbladder membranes so that the transduction of smooth muscle regulatory signals is impaired, and it may enhance the inflammation-induced mucin secretion by the gallbladder. To achieve a better understanding of the mechanism by which supersaturated bile impairs the contractility, we studied changes in the expression levels of gallbladder cholecystokinin (CCK-A) receptor messenger ribonucleic acid (mRNA) in prairie dogs fed a high-cholesterol diet. Levels of pathobiological determinants in arachidonate metabolism which are important for mucin secretion were also measured in their bile. Adult male prairie dogs were randomly assigned to receive either a semisynthetic diet (SSD) or an SSD plus 1.2% cholesterol (a high-cholesterol diet) for 2-, 4-, and 6-week periods. The contractile force in response to CCK-octapeptide (CCK-8) was measured by using gallbladder muscle strips. The mRNA levels of the CCK-A receptor were determined by reverse-transcription polymerase chain reaction (RT-PCR). Parallel to the increase in the cholesterol saturation index, the contractile responses to CCK-8 decreased in the animals fed a high-cholesterol diet for 4 weeks and markedly decreased in the animals with gallstone formation. However, in contrast to the decreased contractility, the steady-state mRNA levels of the gallbladder CCK-A receptor were significantly increased in the animals fed a high-cholesterol diet in comparison with the corresponding control animals. In the bile, a high-cholesterol diet caused an increase in the proportion of arachidonyl-phosphatidylcholine species, where phospholipase A(2) activity, prostaglandin E(2), and mucin concentrations were increased parallel to the feeding period. Up-regulation of the CCK-A receptor mRNA in the gallbladder of animals fed a high-cholesterol diet associated with decreased contractility may be due to an impairment of CCK signaling related to increased membrane cholesterol contents and its related reaction of biological compensation in order to increase the receptor concentration. The results of the present study suggest that in prairie dogs fed a high-cholesterol diet both a decrease in gallbladder contractility related to impairment of CCK signaling and phospholipase A(2) (PLA(2))-induced mucosal inflammation in the gallbladder with associated biliary alterations favoring cholesterol crystal formation pathogenetically contribute to the formation of cholesterol gallstones.

Animals↗

PubMed1998

Laparoscopic cholecystectomy for acute cholecystitis and the consequences of gallbladder perforation, bile spillage, and "loss" of stones.

OBJECTIVE: To study the factors associated with accidental perforation of the gallbladder and spillage of bile and stones and to assess the consequences of these mishaps. DESIGN: Prospective study with retrospective bacteriological evaluation. SETTING: Teaching hospital, Israel. SUBJECTS: 189 Patients who were treated for clinical acute cholecystitis between January 1994 and August 1996. INTERVENTIONS: Emergency laparoscopic cholecystectomy. MAIN OUTCOME MEASURES: Incidence of accidental perforation of gallbladder and spillage of bile and stones and of conversion and complications in relation to preoperative and operative findings. RESULTS: Bile was spilt in 65 (34%) and gall-stones were "lost" in 27 (14%), 44 (23%) required conversion to an open approach and 36 (19%) developed complications. Preoperative duration of symptoms >96 hours and a palpable gallbladder were associated with accidental perforation of the gallbladder and spillage of bile. A palpable gallbladder, gangrenous cholecystitis, and WBC > 15 x 10(9)/L were associated with stones "lost" in the peritoneum. A history of biliary disease was inversely related to "lost" stones. Conversion of laparoscopic to open cholecystectomy was associated with male sex, age >60 years, a non-palpable gallbladder, WBC > 15 x 10(9)/L, and a gangrenous gallbladder. Complications of surgery were more common among men and associated with fever of >38 degrees C. Neither the conversion nor the complications were associated with perforation of the gallbladder or "lost" stones. CONCLUSION: Perforation of the gallbladder and intraperitoneal spillage of bile or stones during laparoscopic cholecystectomy for acute cholecystitis are not associated with undesirable events, are not indications for conversion, and are not associated with further complications. When patients are given appropriate antibiotics perioperatively and the spilt bile is properly aspirated and the peritoneum irrigated, the operative and postoperative courses are similar to those of patients with unperforated gallbladder.

Acute Disease↗

PubMed2000

Is there a human fetal gallbladder contractility during pregnancy?

The purpose of this study was to evaluate whether human fetal gallbladder contractility exists in the second half of pregnancy. Ultrasound examinations were performed on 54 normal pregnant women from 20 to 40 weeks of gestation. Fetal gallbladder volume was monitored every 30 min from 08:00 to 18:00 h in each patient. Maximum gallbladder volume was related linearly with gestational age between 20 and 32-35 weeks of gestation, after which a plateau was observed. Minimum gallbladder volume was unchanged throughout gestation. Functional capacity (maximum volume - minimum volume) of the fetal gallbladder increased linearly with advancing gestation until 32-35 weeks gestation, and thereafter was constant. Contractility rate [(maximum volume - minimum volume/maximum volume)x100] increased curvilinearly with advancing gestation (R(2) = 30.7%, P < 0.0001). The daily change in fetal gallbladder volume showed a typical sinusoidal pattern, and the contractility cycle of gallbladder volume was unchanged during pregnancy (3.1 +/- 0.6 h). These results suggest that there is an apparent gallbladder contractility in human fetuses in utero, and that maternal meals seem not to affect the volume of the fetal gallbladder. Further study is needed to clarify the physiological role of fetal gallbladder contractility during pregnancy.

Female↗

PubMed1997

Epidemiologic aspects of gallbladder cancer: a case-control study of the SEARCH Program of the International Agency for Research on Cancer.

BACKGROUND: There are few previous epidemiologic studies of gallbladder cancer, a rare but nearly always lethal gastrointestinal cancer with a demonstrated greater frequency in adult women and older subjects of both sexes, and also in the members of populations throughout central and eastern Europe and certain racial groups such as native American Indians. Unfortunately, the prospects for the prevention of this form of cancer are poor. PURPOSE: Our purpose in conducting this study was to investigate possible new risk factors for gallbladder cancer and to strengthen our understanding of established causal agents that may be involved in this disease. METHODS: A large, collaborative, multicenter, case-control study of cancer of the gallbladder was conducted in five centers located in Australia (Adelaide), Canada (Montreal and Toronto), The Netherlands (Utrecht), and Poland (Opole) from January 1983 through July 1988. Case subjects with gallbladder cancer were accrued by the centers from hospital pathology records and from reports to regional cancer registries. Cancer diagnosis was confirmed by either biopsy, cholecystectomy, or at the time of autopsy. Control subjects were randomly assigned at each center from the population. The pooled analysis included 196 case subjects and 1515 control subjects (who did not report previous cholecystectomy). Ninety-eight percent of the subjects were white. Personal interviews of case subjects, control subjects, and surrogates (spouse or next of kin) were conducted by trained personnel. RESULTS: After adjusting for potential confounding factors (age, sex, center, type of interview, years of schooling, alcohol intake, and lifetime cigarette smoking), a history of gallbladder symptoms requiring medical attention (e.g., reduced bile secretion from the gallbladder into the small intestine due to obstructions of the common bile or cystic ducts) was the major risk factor associated with this form of cancer (odds ratio [OR] = 4.4; 95% confidence interval [CI] = 2.6-7.5). This association was present even in subjects who had their first gallbladder examination because of symptoms present more than 20 years earlier (OR = 6.2; 95% CI = 2.8-13.4). Other variables associated with gallbladder cancer risk included an elevated body mass index, high total energy intake, high carbohydrate intake (after adjustment for total energy intake), and chronic diarrhea. All of these risk factors have been previously associated with gallstone disease. CONCLUSIONS: These findings are consistent with a major role of gallstones, or risk factors for gallstones, in the cause of gallbladder cancer. Additional information on whether or not screening high-risk subjects for gallstones or gallbladder cancer is needed.

Adult↗

PubMed1990

Low incidence of hospitalization with gallbladder disease among blacks in the United States.

Low rates of gallbladder disease among blacks have been reported but not systematically studied. The authors investigated the rate of hospitalization with a diagnosis of gallbladder disease in the follow-up in 1982-1984 of the first National Health and Nutrition Examination Survey, a population-based study conducted across the United States in 1971-1975. Based on hospital discharge diagnoses of gallbladder disease, 368 cases were identified for the period 1971-1984 among 10,551 persons, aged 25-74 years, who denied gallbladder disease at the baseline examination. The crude incidence of gallbladder disease per 1,000 person-years was 2.59 for white men, 1.45 for black men, 4.09 for white women, and 2.35 for black women. Controlling for obesity, parity, ethanol consumption, use of diuretics, use of oral contraceptives, and two indicators of socioeconomic status, the authors found that the hazard rate of hospitalization with gallbladder disease increased with age for white women and decreased for black women. The hazard ratio for black women compared with white women at 30 years of age was 0.71 with a 95% confidence interval of 0.52-0.96, but at age 70, it was 0.18 with a 95% confidence interval of 0.09-0.37. For women, obesity and parity were important risk factors for gallbladder disease (p less than or equal to 0.001), and the use of diuretics was marginally associated (p = 0.08). Black men compared with white men had a hazard rate of gallbladder disease of 0.53 with a 95% confidence interval of 0.24-1.16. For men, increasing age was related to gallbladder disease (p less than 0.001), and obesity was weakly related (p = 0.06). The black/white hazard ratios decreased further when controlling for socioeconomic status, persisted if the study population was limited to those hospitalized during follow-up, and increased slightly for cases with an acute complication of gallbladder disease. Thus, differential access to medical care may not explain the lower rate among blacks.

Adult↗

PubMed1981

Release of cholecystokinin in man: correlation of blood levels with gallbladder contraction.

Although it is generally assumed that release of cholecystokinin (CCK) is the chief mechanism by which a fatty meal causes contraction of the gallbladder, measured release of CCK and gallbladder contraction have never been correlated. We have achieved this correlation in eight adult male volunteers, by means of a specific radioimmunoassay for CCK and by ultrasonographic imaging of the gallbladder. This study validates our CCK radioimmunoassay and correlates measured concentrations of CCK with changes in gallbladder size measured by ultrasonographic examination. Basal concentrations of CCK (82.6 +/- 10.4 pg/ml) rose significantly to a maximum of 411.1 +/- 79.9 pg/ml at 16 minutes after intraduodenal instillation of medium-chain triglyceride (Lipomul). Mean basal volume of the gallbladder was 34.6 cm3; maximum reduction of gallbladder volume (to one-third of original) was achieved at 18 minutes. Elevated CCK concentrations began to fall toward basal, and the gallbladder began to refill at 25 minutes. Results obtained after oral ingestion of Lipomul provide similar results. Linear regression analysis demonstrated excellent correlation between concentrations of CCK and gallbladder size during both contraction and relaxation phases. Future study of this correlation may be useful in patients with manifest dysfunction of the gallbladder, as well as in individuals known to be at risk of gallbladder disease.

Adult↗

PubMed1991

Gallbladder dynamics in patients with irritable bowel syndrome and essential dyspepsia.

To assess whether gallbladder motility is altered in patients with irritable bowel syndrome (IBS) or essential dyspepsia (ED), we studied gallbladder function in 25 healthy volunteers, 20 patients with IBS, and 22 with ED. By real time ultrasonography, we studied the following parameters: (a) fasting gallbladder volume, (b) maximum percent of gallbladder emptied, (c) time required for maximal contraction, (d) residual volume after maximal contraction, and (e) percent fasting volume at 2 h. All parameters, except fasting gallbladder volume, were measured after a high-fat meal. The fasting gallbladder volume, maximum percent of gallbladder emptied, time required for maximal contraction, residual volume after maximal contraction, and percent fasting volume at 2 h in controls and patients with IBS was 19.3 +/- 8.8 ml and 24.4 +/- 9.7 ml, 67.1 +/- 10.7% and 67.6 +/- 13.5%, 41 +/- 20.6 min and 49.7 +/- 25.3 min, 6.2 +/- 3.3 ml and 7.6 +/- 5.3 ml, and 38.1 +/- 12.2% and 40.7 +/- 14.5%, respectively. The differences between the two groups were statistically not significant. The corresponding values in patients with ED were 15.5 +/- 6.3 ml, 57.6 +/- 16.5%, 51.8 +/- 29.3 min, 6.1 +/- 3.2 ml, 44.1 +/- 17%, respectively. Compared with controls there was no statistically significant difference in these parameters, except the maximum percent of gallbladder emptied, which was significantly less than that in controls (57.6 +/- 16.5% vs. 67.1 +/- 10.7%; p less than 0.05). Therefore, we could not find that patients with IBS have any abnormality of gallbladder function; postprandially, patients with ED have submaximal contraction of the gallbladder.

Adolescent↗

PubMed2003

Tip for microlaparoscopic cholecystectomy: easy removal of the gallbladder after laparoscopic cholecystectomy using the three-port technique.

The standard laparoscopic cholecystectomy usually requires four trocars: two 10-mm and two 5-mm trocars. With the development of mini-instruments, laparoscopic surgeons have developed the two- or three-port techniques. The selection of the number and size of trocars depends on the surgeon's experience and preferences. Removal of the gallbladder is critical in the mini-instrument technique. To remove the gallbladder through the umbilical port, a 5-mm telescope should be inserted through one of the 5-mm ports, or one of the 5-mm trocars should be replaced with an 11-mm trocar by extending the incision. A simple and easy technique was applied to retrieve the gallbladder without changing the telescope or extending the skin incision for the trocar port to 11 mm. When the gallbladder is detached from the liver, the surgeon grasps the neck of the gallbladder via the 5-mm trocar and positions the gallbladder in the 11-mm trocar. While the surgeon keeps the gallbladder in the 11-mm trocar with the grasper held tangentially, the assistant removes the telescope and inserts a straight-toothed grasper to capture the gallbladder neck blindly. Subsequently, the removal of the gallbladder together with the trocar follows the usual technique. We have applied this technique to all our patients with limited or no inflammation of the gallbladder.

Cholecystectomy, Laparoscopic↗

PubMed1995

Effects of cholestyramine on gallbladder and gastric emptying in obese and lean subjects.

Gallbladder stasis is frequent in obese subjects and may contribute to their increased risk for gallstone formation. The bile salt sequestrant cholestyramine acutely enhances postprandial gallbladder emptying in lean subjects, through disinhibition of a negative feedback between intraluminal bile salts and CCK release. In this study the effect of cholestyramine on both gallbladder and gastric antrum dynamics were studied by real-time ultrasonography in 12 obese and 15 lean subjects. For the acute study, on different days, subjects ingested a liquid meal (two egg yolks plus water 200 mL, 50 kJ) or a meal with 4 g cholestyramine. Gallbladder emptying was impaired in obese patients who had significantly larger fasting gallbladder volume (39.4 +/- 6.9 vs. 21.6 +/- 1.7 mL, P < 0.02), larger residual volume (12.3 +/- 1.8 vs. 4.0 +/- 0.5 ml, P < 0.0006) and slower emptying time (T/2: 33 +/- 2 vs. 21 +/- 2 min, P < 0.05) than lean subjects. Integrated antral emptying was also less in obese than lean subjects (5521 +/- 578 vs. 7908 +/- 491 %120 min-1, P < 0.02). Cholestyramine enhanced postprandial gallbladder emptying in both obese and lean subjects. Gastric emptying was delayed with cholestyramine in lean but not obese subjects. For the chronic study, after 1 month therapy with cholestyramine (4 g every 2 days), the motility tests were repeated in nine obese subjects. Gallbladder and gastric responses to a test meal, with or without cholestyramine, were preserved. We conclude that both gallbladder and antral emptying of a liquid test meal are impaired in obese subjects. Gallbladder emptying improves after acute administration of a low dose cholestyramine with test meal. This effect is sustained after 1 month treatment with a low dose of cholestyramine and does not interfere with gastric emptying of obese patients. Cholestyramine may improve gallbladder hypomotility in obese people.

Adolescent↗

PubMedDate not supplied

Prevalence of gallbladder sludge in dogs as assessed by ultrasonography.

Ultrasonography of the gallbladder was performed in 3 groups of dogs: 30 clinically healthy dogs, 50 dogs with hepatobiliary disease, and 50 dogs with diseases other than hepatobiliary disease. The gallbladder was evaluated for the presence of sludge (echogenic material without acoustic shadowing). Maximal gallbladder length, width, height, and area were measured as well as the gallbladder wall thickness. The relative sludge area was calculated as the ratio of sludge area over gallbladder area on longitudinal images. No significant difference was found in the prevalence of gallbladder sludge among healthy dogs (53%), dogs with hepatobiliary diseases (62%), and dogs with other diseases (48%). The mean age of dogs with sludge was higher than the mean age of dogs without sludge in dogs with hepatobiliary disease and dogs with other diseases (p < 0.05). The mean relative sludge area did not differ significantly among the 3 groups. A trend to larger gallbladder dimensions in dogs with sludge compared to dogs without sludge was detected within the 3 groups. The gallbladder wall thickness was not different between dogs with and without sludge within the 3 groups. However, the gallbladder wall was more frequently isoechoic than hyperechoic to the liver in dogs with sludge than in dogs without sludge. The results of this study indicate that gallbladder sludge, in dogs, is not particularly associated with hepatobiliary disease and should be considered an incidental finding.

Animals↗

PubMed2002

Muscarinic receptor knockout mice: role of muscarinic acetylcholine receptors M(2), M(3), and M(4) in carbamylcholine-induced gallbladder contractility.

Muscarinic receptors play a major role in gallbladder function, although the muscarinic receptor(s) mediating smooth muscle contractility is unclear. This study compared smooth muscle contractile responses to carbamylcholine (10(-7)-10(-3) M) in isolated gallbladder from wild-type and M(2), M(3), and M(4) receptor knockout mice. Carbamylcholine-induced contraction in gallbladder was associated with tachyphylaxis and the release of a cyclooxygenase product because indomethacin (10(-6) M) inhibited carbamylcholine-induced contraction. The M(3) receptor was the major muscarinic receptor involved in contraction because carbamylcholine-induced contractility was inhibited in gallbladder from M(3) receptor knockout mice. Furthermore, the muscarinic receptor antagonists 11-[[[2-diethylamino-O-methyl]-1-piperidinyl]acetyl]-5,11-dihydrol-6H-pyridol[2,3-b][1,4]benzodiazepine-6-one (AF-DX 116) and pirenzepine dextrally shifted contraction to carbamylcholine in gallbladder from wild-type, M(2), and M(4) receptor knockout mice, with affinities consistent with M(3) receptor interaction. In addition, maximal contraction to carbamylcholine was reduced in gallbladder from M(2) receptor knockout mice and affinities for AF-DX 116 and pirenzepine in gallbladder from M(3) receptor knockout mice were consistent with their affinities at M(2) receptors. In M(4) receptor knockout mice, contraction to carbamylcholine was dextrally shifted, although the affinities for AF-DX 116 and pirenzepine in gallbladder from M(2) or M(3) knockout mice were not similar to their affinities at M(4) receptors. The M(4) receptor may serve as an accessory protein necessary for optimal potency of M(2) and M(3) receptor-mediated responses. Thus, muscarinic receptor knockout mice provided direct and unambiguous evidence that M(3), and to a lesser extent, M(2) receptors are the predominant muscarinic receptors mediating gallbladder contractility, and M(4) receptors appear necessary for optimal potency of carbamylcholine in gallbladder contraction.

Animals↗

PubMed1970

Vagotomy and gallbladder function.

The effect of vagotomy on gallbladder function was investigated in a clinical and experimental study. In the clinical study both the size of the gallbladder and its capacity to respond to cholecystokinin were evaluated radiologically before and after vagotomy. In studies in the rabbit, both the immediate effect of vagotomy on the gallbladder and the effect of varying doses of cholecystokinin on gallbladder pressure were studied before and after vagotomy. In studies in the cat the long-term effect of vagotomy was studied with respect to the histology of the gallbladder and the composition of bile. The clinical investigation showed that vagotomy was followed by a significant increase in the volume of the gallbladder and that the effect of the cholecystokinin on the gallbladder remained unchanged after vagotomy. In experiments in the rabbit it was found that cholecystokinin in a dose of 1 unit/kg body weight exerted a somewhat lesser effect on gallbladder pressure after vagotomy than before, while after vagotomy a dose, approximately four times greater, resulted in a stronger gallbladder response. Further, the experiments showed that the chemical composition of the bile seemed to be altered after vagotomy, while the gallbladder remained histologically essentially unchanged.

Adult↗

PubMed1975

Gallbladder function, cholesterol stones, and bile composition.

Gallbladder bile obtained at operation from five patients with no symptoms of biliary disease was undersaturated with cholesterol in every case. However, gallbladder bile from patients with stones composed of 97-100% crystalline cholesterol was on average just saturated with cholesterol when the gallbladder was functioning and undersaturated when it was not. Regardless of gallbladder function, the patients with stones had on average significantly more cholesterol in their bile than in the control group, but the differences between the mean composition of bile from functioning and non-functioning gallbladders were not significant. Common duct bile from patients with non-functioning and functioning gallbladders was on average supersaturated with cholesterol, but there was significantly more bile salt and significantly less cholesterol in the bile from patients with non-functioning gallbladders. Only in the case of patients with functioning gallbladders did the mean composition of the common duct and gallbladder biles differ significantly. The former contained significantly more cholesterol and less bile salt than the latter. It is suggested that patients with non-functioning gallbladders may be 'autocholecystectomised' with the duct bile reverting to a more 'normal' composition.

Bile↗

PubMed2002

Nonvisualization of the fetal gallbladder in early pregnancy: comparison with clinical outcome.

PURPOSE: To prospectively assess the frequency of a nonvisualized fetal gallbladder in early pregnancy and to determine its prognostic value. MATERIALS AND METHODS: Fetal transvaginal ultrasonography (US) was performed in 29,749 consecutive pregnant women at 14-16 weeks gestation. A nonvisualized fetal gallbladder was defined if the gallbladder could not be depicted during two targeted examinations within 1 week. In such cases, women were offered an amniocentesis for fetal karyotype and hepatic enzyme analysis. Repeat transabdominal fetal US was performed at 22-26 weeks' gestation. If the gallbladder was still not depicted, US was performed postnatally. RESULTS: The gallbladder was not visualized in early pregnancy in 34 fetuses (0.1%; incidence of one in 875 pregnancies). Associated structural malformations were detected in 14 of 34 (41%) fetuses, five of which also had an abnormal karyotype. Pregnancy was terminated in nine of these 14 fetuses. In the remaining five patients who continued pregnancy, the gallbladder was detected later in pregnancy in four. However, only one infant was healthy. Nonvisualization of the gallbladder as an isolated finding was noted in 20 of 34 (59%) fetuses, all of which had a normal outcome. The gallbladder was detected later in pregnancy in 11 of these fetuses and after birth in two neonates, while no gallbladder was detected after delivery in five other neonates. Two patients were lost to follow-up. CONCLUSION: Nonvisualization of the fetal gallbladder in early pregnancy is uncommon but associated in many cases with other fetal anomalies.

Abnormalities, Multiple↗

PubMed1998

Enlarged fetal gallbladder: prognostic importance for aneuploidy or biliary abnormality at antenatal US.

PURPOSE: To test the strength of the association of cholecystomegaly with aneuploidy and biliary abnormality and to assess the prognostic importance of the detection of an enlarged fetal gallbladder at antenatal ultrasonography (US). MATERIALS AND METHODS: Gallbladder size was prospectively evaluated during 842 consecutive second-and third-trimester US examinations in 775 fetuses. The area of the gallbladder was calculated on the image that depicted the maximal gallbladder size, and the actual gallbladder areas was compared with the gallbladder area expected on the basis of the gestational age. Fetuses with an enlarged gallbladder were followed up. RESULTS: Forty-three fetuses had an enlarged gallbladder (area more than 2 SDs above the mean for gestational age). Outcome was normal in 38 of the 39 fetuses who could be followed up. With the exception of a single baby with an isolated ventricular septal defect, which closed spontaneously, none of the babies with an enlarged fetal gallbladder had structural anatomic defects or evidence of aneuploidy or a biliary tract abnormality. CONCLUSION: Identification of an enlarged gallbladder at antenatal US does not appear to be associated with a substantially increased risk of chromosomal aneuploidy or biliary tract malformation.

Aneuploidy↗

PubMed1986

Endogenous cholecystokinin drives gallbladder emptying in dogs.

We investigated the effect of fat in the duodenum on the gallbladder emptying in seven dogs prepared with gastric, duodenal, and gallbladder cannulas. Gallbladder volume was measured at 15-min intervals, and venous blood samples were obtained at regular intervals for 2.5 h. Intraduodenal administration of Lipomul (pH 5.0, corn oil) in three different doses (1.1, 2.2, and 4.4 mmol/10 min) resulted in significant increases in gallbladder emptying in a dose-dependent manner (r = 0.8668, P less than 0.001). Likewise, the increase in integrated cholecystokinin (CCK) release in response to Lipomul was also dose dependent (r = 0.7334, P less than 0.001). A statistically significant correlation was found between integrated CCK release and gallbladder emptying in response to Lipomul (P less than 0.001). To determine the role of circulating endogenous CCK on gallbladder emptying effects of intravenous administration of proglumide and a rabbit anti-CCK serum on gallbladder emptying were studied. Gallbladder emptying was virtually abolished by the antiserum. Proglumide not only abolished the emptying but also increased gallbladder volume. Thus we conclude that in dogs the gallbladder emptying in response to fat in the upper small intestine depends on increased circulating endogenous CCK.

Animals↗

PubMed1988

Canine gallbladder cyclic motor activity.

We investigated whether the gallbladder has cyclic motor activity similar to that of the stomach, lower esophageal sphincter, and sphincter of Oddi in the fasted state. We found that the canine gallbladder infundibulum exhibited a cyclic burst of short duration (69 +/- 3 s) contractions that were closely associated with phase III activity of the antrum. The cyclic motor activity was sometimes less prominent or absent in the body and the fundus of the gallbladder. The mean period of gallbladder cyclic motor activity was not significantly different from the mean period of phase III activity in the stomach and the duodenum. The cyclic bursts of gallbladder contractions lasted for 21 +/- 2 min. The gallbladder cyclic motor activity started at about the same time as the antral phase III activity, and both of these activities started approximately 12 min earlier than the duodenal phase III activity. In addition to the aforementioned cyclic bursts of contractions, the gallbladder sometimes exhibited long duration (6.4 +/- 0.6 min) contractions that occurred irregularly and unpredictably during the duodenal migrating motor complex cycle. We conclude that during fasting the canine gallbladder has a cyclic motor activity that is temporally related to phase III activity of the stomach and the duodenum. The role of short duration phasic contractions during cyclic motor activity may be to periodically stir gallbladder contents, whereas the long duration contractions may partially empty the gallbladder in the fasted state.

Animals↗

PubMed2002

Diminished inibitory action of ethanol on the contraction of gallbladder isolated from chronically ethanol-fed Guinea pigs.

Ethanol is known to decrease the gallbladder contractility. The purpose of this study was to clarify the mechanism of tolerance to the inhibitory action of ethanol on the gallbladder contractility. Male guinea pigs were fed ethanol (3%) or calorie-matched sucrose in the drinking water for 4 weeks. Then, the gallbladder was isolated, and its isometric tension was measured. The contractile responses to KCl, BAY K8644, histamine, and phorbol 12,13-dibutyrate in the normal medium were not different between the gallbladder strips from ethanol-fed and control guinea pigs. Ethanol at 25 mmol/l in vitro did not affect the contractile responses to KCl and BAY K8644 in the gallbladder strips from both ethanol-fed and control guinea pigs. On the other hand, ethanol at 25 mmol/l in vitro significantly inhibited the contractile responses to histamine and phorbol 12,13-dibutyrate in the gallbladder strips from the control guinea pigs, but it did not affect the contractile response to histamine and significantly augmented that to phorbol 12,13-dibutyrate in the strips from the ethanol-fed guinea pigs. Diphenhydramine, a selective H(1) receptor antagonist, abolished the histamine contraction in gallbladder strips from both control and ethanol-fed guinea pigs, while cimetidine, a selective H(2) receptor antagonist, did not affect histamine contraction, implying that histamine-induced contraction of guinea pig gallbladders is mediated only by H(1) receptors. Verapamil (1 micromol/l) completely inhibited the phorbol 12,13-dibutyrate-induced contraction of the strips from both ethanol-fed and control guinea pigs. The histamine-induced contraction was partly inhibited in the absence of Ca(2+) in the medium. In the gallbladder strips from both ethanol-fed and control guinea pigs, ethanol at 25 mmol/ in vitro did not affect the histamine-induced contraction in the absence of extracellular Ca(2+). Tolerance to the inhibitory action of ethanol developed selectively on contractile responses to histamine and phorbol 12,13-dibutyrate. Chronic ethanol administration produces tolerance to in vitro gallbladder contractility mediated by the Ca(2+) entry through L-type Ca(2+) channels linked with protein kinase C activation.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗