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PubMed2000

Expression of platelet-derived endothelial cell growth factor/thymidine phosphorylase in human gallbladder lesions.

The aim of this study was to investigate the expression of platelet-derived endothelial growth factor (PD-ECGF) in human gallbladder carcinomas to elucidate its role in angiogenesis and tumour progression. To this end, 56 archival surgical specimens of gallbladder lesions were examined for PD-ECGF/thymidine phosphorylase (TP) expression by immunohistochemistry and the PD-ECGF/TP protein level was assessed in five fresh specimens of gallbladder carcinoma by enzyme-linked immunosorbent assay (ELISA). Hyperplastic epithelial cells and adenoma cells showed no or faint staining with PD-ECGF/TP. Out of 43 gallbladder carcinomas, 27 (63%) showed moderate to strong immunoreactivity in the cytoplasm and nuclei of the tumour cells. PD-ECGF/TP immunoreactivity in stromal infiltrating cells was detected in 43% (3/7) hyperplasias, 17% (1/6) adenomas and 86% (37/43) carcinomas. PD-ECGF/TP protein levels in carcinoma tissues were higher than those in corresponding normal mucosa. PD-ECGF/TP expression did not correlate with angiogenesis, but significantly correlated with depth of invasion, lymph node metastasis, and tumour stage. These results overall suggest that PD-ECGF/TP produced by both cancer cells and infiltrating cells is associated with tumour progression in human gallbladder carcinoma.

Adenocarcinoma↗

PubMed2006

Metastatic renal cell carcinoma of the gallbladder.

A 73-year-old man presented for further evaluation of a gallbladder polyp, 5 years after left radical nephrectomy for renal cell carcinoma (RCC). Computed tomography revealed a 2-cm enhancing pedunculated tumour within the gallbladder. Open simple cholecystectomy was performed and the tumour was histologically confirmed as a metastasis of the RCC to the gallbladder. The patient is alive and disease-free, 2 years after cholecystectomy. Of the reported 23 patients with metastatic RCC of the gallbladder, nine patients were reported to be cancer-free with the longest follow-up interval of 6 years after cholecystectomy. Although metastasis of RCC is a rare differential diagnosis of gallbladder tumours, simple cholecystectomy may offer a chance of long-term survival for patients with RCC.

Aged↗

PubMedDate not supplied

Heat ablation of the normal gallbladder in pigs.

PURPOSE: The safety and efficacy of ablating gallbladder mucosa was investigated with a percutaneously placed heater catheter in an animal study. MATERIALS AND METHODS: The study was performed in three stages with 39 pigs. In stage 1 (15 heat-treated animals, one control), the configuration of the heater catheter was progressively improved and the temperature settings for stage 2 were defined. In stage 2 (11 heat-treated animals, four controls), the predetermined settings were used with mechanical mixing and cystic duct ligation to test for safety and efficacy. In stage 3 (eight animals), prior heat ablation of the cystic duct was added to reduce epithelial regeneration. RESULTS: Gallbladder ablation was achieved at temperatures below 60 degrees C. Mechanical mixing of the intraluminal contents was essential for even heat distribution for ablation and to reduce the incidence of adjacent organ damage. Thermal injury to adjacent organs occurred when gallbladder ablation temperature exceeded 54 degrees C and serosal temperatures of adjacent organs exceeded 43 degrees C. Thermal ablation at 54 degrees C for 35 minutes was completely successful in 25%, partially successful in 50%, and failed in 25% of animals. Cystic duct ablation improved overall results and appears vital in removing duct epithelium as a source for regeneration of the mucosal lining. CONCLUSION: Defunctionalization of the retained gallbladder is potentially achievable with use of thermal techniques, but the thermal range between complete gallbladder ablation and adjacent organ injury is narrow.

Animals↗

PubMedDate not supplied

Chemical ablation of the gallbladder: evaluation of multiple agents in vitro.

PURPOSE: To find a more effective chemical regimen for transcatheter ablation of the gallbladder in an in vitro model. MATERIALS AND METHODS: Sectioned and whole pig gallbladders were exposed in vitro to 12 different chemical solutions at varying conditions of exposure time, pH, and temperature. RESULTS: In the in vitro studies, 0.1 N and 1.0 N solutions of sodium hydroxide in water or ethanol and 3% hydrogen peroxide were the most effective sclerosant agents. Ethanol and hydrochloric acid failed to completely eliminate the epithelium from the gallbladder sections. Increasing exposure time from 10 to 20 minutes or increasing the temperature of the solutions from 37 degrees C to 50 degrees C did not alter these results. Sequential 15-minute exposures to 0.1 N sodium hydroxide in ethanol followed by peroxide completely eliminated the epithelium from whole gallbladders in vitro. CONCLUSION: Alkaline solutions and hydrogen peroxide are more effective than ethanol alone, acids, or detergents in eliminating gallbladder epithelium in this model. Further evaluation of these agents in vivo is merited.

Animals↗

PubMed2001

Surgical treatment of patients with T2 gallbladder carcinoma invading the subserosal layer.

BACKGROUND: Because T2 carcinoma of the gallbladder that invades perimuscular connective tissue without extension beyond serosa or into the liver has a hope for longterm survival, we attempted to clarify significant prognostic factors with respect to tumor- and surgery-related variables. STUDY DESIGN: Of 65 patients with gallbladder carcinoma who had undergone surgical resection from 1983 to 1999, 28 had T2 carcinoma histologically proved. The significance of variables for survival was examined by the Kaplan-Meier method and log-rank test followed by multivariate analyses using Cox's proportional hazard model. RESULTS: There were 17 patients with stage II carcinoma (T2 N0 M0), 6 with stage III (T2 N1 M0), and 5 with stage IVB. Lymph node metastasis was present in 11 patients (39%) and it reached to the peripancreatic head region (N2) in 5 of them. Lymphatic, venous, and perineural invasions were found in 68%, 57%, and 43%, respectively. With respect to tumor factors, the absence of perineural invasion (Odds ratio [OR] 16.77, 95% confidence interval [CI] 2.17-129.94, p = 0.0069), absence of lymph node metastasis (OR 15.00, 95% CI 2.08-108.33, p = 0.0073), and stage II (II versus III and IVB, OR 15.00, 95% CI 2.08-108.33, p = 0.0073) were significant factors related to good postoperative survival in the multivariate analysis. Surgical procedure (radical resection versus cholecystectomy, OR 4.31, 95% CI 1.34-13.82, p = 0.0142) and surgical margin (OR 7.41, 95% CI 2.19-25.13, p = 0.0013) were significant factors in the univariate analysis. Cancer-free surgical margins provided a significantly better survival (5-year survival rate, 62%); none with cancer-positive surgical margins survived for more than 27 months. In the multivariate analysis, surgical procedure was significant (OR 25.49, 95% CI 1.62-400.72, p = 0.021). Radical surgery, including extended cholecystectomy (resection of the gallbladder together with the gallbladder bed of the liver) and anatomic resection of liver segment 5 and of the lower part of segment 4, gave a significantly better 5-year survival rate than cholecystectomy (59% versus 17%). The 5-year survival rate after radical resection in patients with stage II was 75%; that in patients with stage III and IVB was 33%. CONCLUSIONS: Results suggest that radical surgery is the treatment of choice for patients with T2 carcinoma of the gallbladder. The presence of lymph node metastasis, perineural invasion, or both suggests the necessity of additional treatment after radical surgery.

Antineoplastic Agents↗

PubMedDate not supplied

Should suspected early gallbladder cancer be treated laparoscopically?

Early gallbladder cancer (EGC), defined as T1 and T2 disease, is frequently curable when completely excised without bile spillage. The objective of the present study was to determine what effect initial laparoscopic cholecystectomy has on outcome in patients with EGC. Of 89 patients referred to our institution with gallbladder cancer over an 11-year period, 26 had undergone initial laparoscopic cholecystectomy. Sixteen of the 26 patients had T1 or T2 disease and are the subjects of this report. These patients were reviewed retrospectively to assess preoperative diagnosis, intraoperative bile spillage, and outcome (recurrence and survival). In addition, the Western literature was reviewed to determine the impact of initial laparoscopic cholecystectomy on recurrence and survival of patients with EGC. Six patients had a preoperative ultrasound consistent with a mass in the gallbladder wall. Seven (44%) had documented bile spillage during the laparoscopic cholecystectomy. T stage based on the laparoscopic cholecystectomy was T1 (n = 1) and T2 (n = 15). Twelve patients underwent reexploration of whom seven underwent further radical excision (gallbladder liver bed resection and extensive lymphadenectomy). After a mean follow-up of 20.1 months (range 4 to 39 months), 69% of patients have had a recurrence or died. Three patients had a port-site recurrence. Five (71%) of seven patients with bile spillage at laparoscopic cholecystectomy have had a recurrence or died of disease. A review of the Western literature on EGC initially removed by laparoscopic cholecystectomy (including the present series) yielded 21 patients with T1 and 42 patients with T2 disease. One-year Kaplan-Meier survival (T1 = 89%, T2 = 71%) and 3-year Kaplan-Meier survival (T1 = 47%, T2 = 40%) of these patients is worse than prior reports for open cholecystectomy. An initial laparoscopic cholecystectomy with its potential for bile spillage can convert potentially curable EGC to incurable disease. Patients with preoperative findings suspicious for gallbladder cancer should undergo open exploration with intent to perform a radical cancer operation as a primary procedure if the diagnosis is confirmed intraoperatively.

Adult↗

PubMedDate not supplied

Cholecystectomy, liver resection, and pylorus-preserving pancreaticoduodenectomy for gallbladder cancer: report of five cases.

Carcinoma of the gallbladder is an uncommon yet highly malignant disease with a poor overall prognosis. Surgical resection offers the only hope for cure in patients with this type of cancer, but resection is often impossible because of advanced disease at the time of presentation. Patients with locally advanced gallbladder cancer, however, may occasionally be amenable to management by adding pancreaticoduodenectomy to cholecystectomy and liver resection. A retrospective review of patient records at the Johns Hopkins Hospital identified five patients with gallbladder cancer with peripancreatic lymph node involvement, who were treated by surgical resection including pancreaticoduodenectomy. The preoperative evaluation, operative technique, pathologic findings, and outcome were reviewed for each patient. Follow-up was obtained via clinic visit or telephone contact. All five patients underwent resection of the gallbladder cancer with an operation that included pylorus-preserving pancreaticoduodenectomy to remove the peripancreatic lymph nodes. In addition, four of the five patients underwent a nonanatomic liver resection. There were no in-hospital deaths. Two patients had postoperative complications; one had persistent drainage from a T-tube site and one had an anastomotic leak from the hepaticojejunostomy. Four patients have died of recurrent tumor during follow-up at intervals ranging from 11 months to 23 months. The fifth patient is alive and free of clinical disease at 42 months after operation. Carcinoma of the gallbladder is a highly malignant disease that is often not amenable to surgical cure. There is a select group of patients, however, in whom adding a pylorus-preserving pancreaticoduodenectomy can result in a potentially curative operation by removing extensive regional spread to the peripancreatic lymph nodes.

Adenocarcinoma↗

PubMed2001

Myosin light chain phosphorylation correlates with contractile force in guinea pig gallbladder muscle.

Acetylcholine (ACh)-induced gallbladder smooth muscle contraction involves myosin light chain phosphorylation (MLCP). ACh-induced contraction is dose dependent. Whether MLCP by ACh is also dose dependent and how it correlates with contractile force have not been carefully evaluated. This study investigated the correlation between gallbladder muscle contraction and MLCP. Guinea pig gallbladder muscle strips were studied isometrically and frozen after different doses of ACh (0, 0.1, 5, 100 microM) for different periods of incubation (0.5, 1, 2, 3, 4 min). MLCP was determined using gel electrophoresis. Both contraction and MLCP in response to ACh were concentration dependent. Peak MLCP to ACh 100 microM occurred at 30 sec. There was a high correlation between active force and MLCP (r = 0.991; P = 0.009 at 30 sec stimulation). Nifedipine 1 microM reduced ACh-induced contraction and MLCP by a similar degree (31% and 33%, respectively). In conclusion, gallbladder contractile force significantly correlates with MLCP. This is consistent with the hypothesis that initiation of gallbladder cholinergic contraction is dependent on phosphorylation of myosin light chains.

Acetylcholine↗

PubMed2000

Evaluation of gallbladder motility in patients with liver cirrhosis: relationship to gallstone formation.

To investigate the postprandial gallbladder motility, including emptying and refilling, in cirrhotic patients and to evaluate the relationship to the presence of gallstones and various humoral mediators, 82 patients with liver cirrhosis and 40 age- and sex-matched healthy subjects were enrolled into this study. Postprandial gallbladder volumes were measured with ultrasonography every 15 min for 2 hr. Plasma levels of estradiol, testosterone, substance P, and nitrate/nitrite were also measured. Cirrhotic patients showed a higher prevalence of gallstones than healthy subjects (41% vs 15%, P = 0.003), and the prevalence increased with the progression of liver cirrhosis (Child-Pugh class A: 26%, B: 44%, and C: 65%, P = 0.02). Plasma levels of estradiol, testosterone, and substance P, and nitrate/nitrite and estradiol/testosterone ratios were not different between cirrhotic patients with and without gallstones. However, postprandial refilling of the gallbladders was significantly impaired in patients with cirrhosis, especially in those combined with gallstones. There was no significant difference in the postprandial gallbladder motility between cirrhotic patients with and without elevated plasma levels of estradiol, testosterone, and substance P and nitrate/nitrite, and estradiol/testosterone ratios. Gallstones were common in patients with liver cirrhosis and the prevalence increased with the progression of liver diseases. Sex hormones, substance P, and nitrate/nitrite did not play major roles in the formation of gallstones in cirrhotic patients. Refilling of the gallbladder was significantly impaired in patients with liver cirrhosis, especially in those with gallstones, and may play an important role in the pathogenesis of gallstones.

Aged↗

PubMed2001

Gallbladder vasculitis associated with type-1 cryoglobulinemia.

A patient with type I cryoglobulinemia and monoclonal gammopathy of uncertain significance was found to have acute gallbladder vasculitis. The most prominent manifestation was upper abdominal pain in the setting of normal liver tests. An abdominal ultrasound demonstrated a thickened gallbladder wall, along with gallstones. HIDA scanning showed a nonfunctioning gallbladder with an edematous and thickened wall. There was characteristic leukocytoclastic vasculitis affecting the gallbladder. The patient recovered uneventfully subsequent to cholecystectomy. Gallbladder vasculitis should be considered in patients with unexplained upper abdominal pain and systemic vasculitis.

Abdominal Pain↗

PubMed2001

Interdigestive gallbladder emptying, antroduodenal motility, and motilin release patterns are altered in cholesterol gallstone patients.

The role of interdigestive gallbladder emptying in gallstone formation is unknown. In fasting healthy subjects, gallbladder emptying is associated with antral phase III of the migrating motor complex (MMC) and high plasma motilin. Therefore, gallbladder volumes and motilin levels were measured during 13 MMC cycles in 10 cholesterol gallstone patients and compared with 20 MMC cycles in 10 healthy subjects. MMC cycle length was longer in gallstone patients than in healthy subjects (158.2 +/- 17.0 vs 105.5 +/- 10.4 min, respectively; P < 0.05), due to longer phase I (39.8 +/- 5.7 vs 17.2 +/- 3.7 min, respectively; P < 0.05). In contrast to healthy subjects, gallstone patients had no significant fluctuations of gallbladder volume during the MMC cycle, and motilin concentrations were not different in MMC cycles with phase III originating in antrum or duodenum. During MMC cycles with phase III originating in the duodenum, motilin levels were twice as high in gallstone patients as in healthy subjects (P < 0.002). In conclusion, cholesterol gallstone patients have an abnormal MMC and motilin release pattern. Their interdigestive gallbladder emptying is reduced and dissociated from the MMC. These disturbances may contribute to gallstone formation.

Cholelithiasis↗

PubMed2002

Endothelin content, expression, and receptor type in normal and diseased human gallbladder.

The aims of this study were to characterize the endothelin (ET) system in human gallbladder by determining (1) the tissue content of ET-1 and ET-2 by ELISA; (2) the expression of mRNA of the ET precursors preproendothelin-1, -2, and -3; and (3) mRNA expression for the ETA and ETB receptors. Median content of ET-1/2 was significantly reduced in severely inflamed gallbladders compared to gallbladders with mild inflammation. There was an inverse correlation between content of ET-1/2 and inflammation score. mRNA for preproendothelin-2 was highly expressed in all samples, whereas mRNA for preproendothelin-1 was present in negligible quantities and mRNA for preproendothelin-3 was undetectable. mRNA for ETA receptors was expressed in all samples analyzed, whereas mRNA for ETB receptors was expressed at a much lower level. This study demonstrates the presence of ET-1/2 in human gallbladder. ET-1/2 content is decreased with increasing degrees of histological inflammation. ET-2 is likely to be the physiologically significant endothelin isopeptide expressed and ETA receptors appear to predominate in the human gallbladder.

Cholecystitis↗

PubMed2002

Fatal spontaneous gallbladder variceal bleeding in a patient with alcoholic cirrhosis.

Gallbladder varices are unusual ectopic varices that may develop in patients with portal hypertension, particularly in those with portal vein occlusion. In rare instances, these varices may cause hemobilia, life-threatening bleeding, or even rupture of the gallbladder. We report the first case of a 41-year-old man with alcoholic cirrhosis and patent portal vein who developed massive hemoperitoneum from spontaneous rupture of varices in the gallbladder fossa. The diagnosis of gallbladder varices eluded conventional imaging and was made only at autopsy. Gallbladder variceal hemorrhage is a rare, but potentially catastrophic complication of cirrhosis.

Adult↗

PubMed2004

Gallbladder cancer treatment using adenovirus expressing the HGF/NK4 gene in a peritoneal implantation model.

Gallbladder cancer cells are stimulated by hepatocyte growth factor (HGF) in vitro and in vivo. We constructed an adenovirus vector, AdCMV.NK4, carrying the HGF antagonist HGF/NK4 (NK4) and evaluated whether or not this vector can suppress the peritoneal implantation of gallbladder cancer in a novel peritoneal injury mouse model. A human gallbladder cancer cell line (GB-d1) and human peritoneal mesothelial cells infected with the adenovirus vector produced a substantial level of NK4 protein. An invasion of GB-d1 cells was determined by a coculture with AdCMV.NK4-infected human mesothelial cells in vitro. Both the invasion and migration of GB-d1 cells were dramatically inhibited by this vector in a multiplicity of infection (MOI)-dependent manner. GB-d1 cells were intraperitoneally injected into the nude mice with peritoneal injury, followed by either AdCMV.NK4 or a control vector (AdCMV.LacZ). The incidence and the size of the metastatic tumor drastically decreased by AdCMV.NK4 (MOI 100: n=4, P<.0001). Real-time PCR analysis revealed a transient elevation of mouse HGF mRNA expression at the peritoneal injury sites. AdCMV.NK4 has been suggested to induce the inhibition of the implantation and growth of gallbladder cancer cells in vivo through its anti-HGF activity, and the use of NK4 gene transfer could be an effective modality for preventing peritoneal metastasis of gallbladder cancer.

Adenoviridae↗

PubMed1994

Heterogeneity of human gallbladder mucin in bile.

1. Human gallbladder mucin has been implicated to play a role in gallstone disease. In spite of this fact relatively little is known about the structure of human gallbladder mucin. In this study we have investigated the possible heterogeneity of mucin. For this purpose polyclonal and monoclonal antibodies against gallbladder mucin were raised. All antibodies reacted primarily with carbohydrate antigenic determinants. With these antibodies the immunoreactivity of gallbladder mucin from 60 patients with cholesterol gallstones and 20 subjects without stones was screened. In addition, reactivity with several lectins was studied. 2. Considerable heterogeneity was found with both antibody and lectin typing, but there was no significant difference in heterogeneity between mucin from patients with gallstones and control subjects. Immunoblotting revealed that there was similarity between the reaction of the polyclonal antibody and the Helix pomatia agglutinin. All mucin preparations reacting with the polyclonal antibody also bound to Helix pomatia agglutinin. Nineteen of the 21 reacting mucins (90%) were from patients with blood group A (18 patients) or AB (one patient) and expression of A antigen could be demonstrated on the mucin of these patients. The resulting two reacting mucins were from patients with type O. However, expression of the blood group antigen could not account for the lack of reactivity of the mucin of other patients. The Helix pomatia agglutinin partially blocked the reactivity of the polyclonal antibody, whereas anti-A antibody did not show inhibition, indicating that more than only blood group A epitopes were recognized by this antibody. 3. We conclude that considerable patient to patient heterogeneity of human gallbladder mucin exists.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibody Specificity↗

PubMed1996

Presence of the NHE3 isoform of the Na+/H+ exchanger in human gallbladder.

1. In man and in various animal species, absorption of NaCl from bile by the gallbladder mucosa is associated with luminal proton secretion. A similar absorption of NaCl in small intestine, colon and renal tubule is related, at least in part, to the presence of the NHE3 isoform of the Na+/H+ exchanger. This work was designed to find out whether NHE3 is also present in human gallbladder. 2. At surgery, 100-200 mg of the gallbladder wall was obtained from patients treated by cholecystectomy for gallstones. After isolation of the mucosa, total RNA was extracted and submitted to reverse transcription-polymerase chain reaction with two primers: 5'-AAGCCICTGGTGCAGTGGCTGAAGG-3' and 5'-GGAGTCCTTIAAGTCGGCIAAGCTGGGC-3', designed to amplify a sequence of 645 bp of rabbit NHE3 mRNA (642 bp in man). RNA from human liver and from rabbit heart, neither of which contain NHE3, and human ileal RNA, which does contain NHE3, were used as controls. 3. RNA extracted from the mucosal moiety of the gallbladder wall gave an amplification product of about 645 nucleotides. Controls gave the expected negative or positive results. Sequencing of the amplified RNA showed it was almost identical to previously determined sequences of NHE3 in other human tissues. 4. It is concluded that the mucosa of human gallbladder contains the mRNA of NHE3 isoform. This isoform could therefore play a role in sodium absorption from bile.

Animals↗

PubMed1996

VIP-antiserum and indomethacin inhibit calcium and bicarbonate secretion by the inflamed feline gallbladder mucosa.

Ionized calcium (Ca2+) and bicarbonate (HCO(3)-) are important ions for gallstone formation. In the present study the effect of indomethacin and vasoactive intestinal peptide-antiserum (VIP-antiserum) on the Ca2+, HCO(3)- and fluid secretion in the inflamed gallbladder were tested in a validated experimental model in cats. The animals were studied in acute experiments 6 weeks after cystic duct ligation and gallstone implantation. During basal conditions there was a continuous secretion of Ca2+, HCO(3)- and fluid into the lumen of the inflamed gallbladder. Indomethacin and VIP-antiserum inhibited the Ca2+, HCO(3)- and fluid secretion across the inflamed gallbladder mucosa. Intraluminal amiloride inhibited the absorption of Ca2+, HCO(3)- and fluid after indomethacin infusion. An impaired absorption of Ca2+, HCO(3)- and fluid in the inflamed gallbladder is probably important for the solubility of calcium salts in the early stages of inflammation in the gallbladder mucosa.

Animals↗

PubMed1999

Effect of somatostatin on human gallbladder motility: an in vitro study.

In vivo studies have demonstrated that somatostatin induces human gallbladder relaxation. To determine whether this polypeptide acts directly on the gallbladder muscle, its effect on strips of human gallbladder was studied in vitro. Strips of gallbladder were set up isometrically in an organ bath containing oxygenated Krebs' solution. Dose-response curves to cholecystokinin-octapeptide and carbachol were first established. The ability of somatostatin to cause relaxation under basal conditions and during 50% maximal stimulation by cholecystokinin-octapeptide (7.2 x 10(-8) M) and carbachol (3.5 x 10(-6) M) was assessed in 32 strips at 4.3 x 10(-6) M concentration which mimics the plasma concentrations found in patients with somatostatinoma and in 12 additional strips at 4.3 x 10(-8) M concentration. Somatostatin action on the intrinsic innervation by using electrical field stimulation (EFS) (200 mA 5 msec in duration, 30 Hz; 400 mA, 1 msec in duration, 10 Hz) was also evaluated in 39 strips. Somatostatin had no effect on the basal or carbachol-generated tensions. On the contrary, somatostatin (4.3 x 10(-6) M) reduced cholecystokinin-octapeptide-generated tensions by 8% (P < 0.001) and reduced EFS-generated tensions at 30 Hz by 7.7% (P < 0.01) and those at 10 Hz by 41.2% (P < 0.01). All responses to cholecystokinin-octapeptide and carbachol were abolished by dibutyryl-guanosine 3', 5'-cyclic monophosphate (5 x 10(-3) M) and atropine (10(-5) M), respectively (P < 0.0002 and P < 0.0002). All responses to electrical field stimulation were reduced or abolished by tetrodotoxin (2 x 10(-6) M) (P < 0.001 and P < 0.0001, respectively). Our findings show that somatostatin exerts its inhibitory action on the response to cholecystokinin-octapeptide and on the intrinsic innervation of the gallbladder smooth muscle. The probable neurotransmitter is the acetylcholine.

Carbachol↗