Biomedical subjects

J S Cheng

Publications and source records attributed to J S Cheng.

At least 37 records · Page 2Linked to original sources

PubMed2001

Comparison of clinical, serological and histological findings between non-ulcer dyspepsia patients with and without Helicobacter pylori infection.

BACKGROUND AND AIMS: The role of Helicobacter pylori (H. pylori) infection in non-ulcer dyspepsia (NUD) remains controversial. This study investigates the clinical, serological and histological differences between patients with H. pylori-positive and -negative NUD. METHODS: One hundred and eighty consecutive patients with NUD were enrolled from January to December 1998. The severity of symptoms was evaluated by the Tucci's scoring system. The histological changes of gastric mucosa were assessed according to the Updated Sydney System, and a fasting blood sample was obtained to test the serum gastrin and pepsinogen I levels. RESULTS: The H. pylori-positive NUD patients were notably older than H. pylori-negative NUD patients (48.2 +/- 15.9 vs 39.8 +/- 15.7 years, P= 0.001). There were no differences in other clinical factors between the two NUD groups. The serum pepsinogen I levels were considerably higher in H. pylori-positive NUD patients than in H. pylori-negative NUD patients (78.9 +/- 42.2 vs 61.5 +/- 43.3 ng/mL, P<0.01). However, no significant differences in serum gastrin levels were discovered between the two groups. The antrum histological scores for chronic inflammation, acute inflammation, gland atrophy and lymphoid follicles were higher in H. pylori-positive NUD patients than in H. pylori-negative NUD patients (2.09 vs 1.01, P<0.001; 1.22 vs 0.36, P<0.001; 0.76 vs 0.36, P<0.01; 0.33 vs 0.13, P<0.01, respectively). CONCLUSIONS: The present study discovered marked differences in age, serum pepsinogen I levels, histological grades of acute inflammation, chronic inflammation, gland atrophy and lymphoid tissue formation between H. pylori-positive and H. pylori-negative NUD patients. Further investigation of the clinical prognosis of the two groups of patients is necessary.

Adult↗

PubMed2001

A prospective, randomized trial of butyl cyanoacrylate injection versus band ligation in the management of bleeding gastric varices.

Gastric variceal bleeding is a catastrophic event. Both cyanoacrylate injection and banding ligation have been proven to be effective in the management of bleeding gastric varices. This study was performed to compare the efficacy and complications of both the modalities. Cirrhotic patients with a history of gastric variceal bleeding were randomized to 2 groups. The group receiving endoscopic obturation (group A) comprised 31 patients and the group receiving band ligation (group B) comprised 29 patients. Butyl cyanoacrylate and pneumatic-driven ligator were applied, respectively. Treatment was repeated regularly until obliteration of gastric varices. Active bleeding occurred in 15 patients in group A and 11 patients in group B. Initial hemostatic rate (defined as no bleeding for 72 hours after treatment) was 87% in group A and 45% in group B (P = .03). The sessions required to achieve variceal obliteration and obliteration rates were similar in both the groups. However, rebleeding rates were significantly higher in group B (54%) than group A (31%) (P = .0005). Treatment-induced ulcer bleeding occurred in 2 patients (7%) in group A and 8 patients (28%) in group B (P = .03). The amount of blood transfusions required were also higher in group B than group A (4.2 +/- 1.3 vs. 2.6 +/- 0.9 units, respectively) (P < .01). Nine patients of group A and 14 patients of group B died (P = .05). In conclusion, endoscopic obturation using cyanoacrylate proved more effective and safer than band ligation in the management of bleeding gastric varices.

Adult↗

PubMed2001

The effects of endoscopic variceal ligation and propranolol on portal hypertensive gastropathy: a prospective, controlled trial.

BACKGROUND: Endoscopic treatment of esophageal varices may accentuate portal hypertensive gastropathy. The impact of the combination of band ligation and propranolol on this condition remains unknown. METHODS: Patients with history of variceal bleeding were randomized to receive band ligation alone (control group, 40 patients) or a combination of band ligation and propranolol (propranolol group, 37 patients). Serial endoscopic evaluation of gastropathy was performed. Gastropathy was classified into 3 grades and scored as 0, 1, or 2. RESULTS: Before endoscopic treatment, 17% of the control group and 22% of the propranolol group had gastropathy (p = 0.78). The occurrence of gastropathy after endoscopic treatment was significantly higher in the control group than in the propranolol group (p = 0.002). Serial endoscopic follow-up revealed that the mean gastropathy score was significantly higher in the control group than in the propranolol group (p < 0.05). In patients with gastropathy the gastropathy score reached a peak at 6 months after endoscopic treatment in both the control and propranolol groups (85% vs. 48%, respectively). After variceal obliteration, accentuation of gastropathy was significant in the control group (p < 0.01) but not in the propranolol group. Gastropathy was less likely to develop in patients who developed gastric varices. Esophageal variceal recurrence was not related to the development of gastropathy after variceal obliteration with banding. Only one patient in the control group bled from gastropathy. CONCLUSION: Band ligation of esophageal varices may accentuate gastropathy, which in this study was partly relieved by propranolol.

Adult↗

PubMed2001

Characterization of histamine-induced increases in intracellular free Ca2+ concentrations in Chang liver cells.

The effect of histamine on intracellular free Ca2+ levels ([Ca2+]i) in Chang liver cells were investigated by using fura-2 as a Ca2+ dye. Histamine (0.2-50 microM) increased [Ca2+]i in a concentration-dependent manner with an EC50 value of 0.8 microM. The [Ca2+]i response comprised an initial rise, a slow decay, and a sustained phase. Extracellular Ca2+ removal inhibited 50% of the maximum [Ca2+]i signal and abolished the sustained phase. After pretreatment with 5 microM histamine in Ca2+-free medium for 4 min, addition of 3 mM Ca2+ induced a [Ca2+]i increase with a magnitude 7-fold greater than control. In Ca2+-free medium, after treatment with 1 microM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor), 5 microM histamine failed to increase [Ca2+]i. Histamine (5 microM)-induced intracellular Ca2+ release was abolished

Calcium↗

PubMed2001

Effect of somatostatin on the sphincter of Oddi in patients with acute non-biliary pancreatitis.

BACKGROUND: Somatostatin has been used to prevent pancreatitis after endoscopic retrograde cholangiopancreatography but its effect on acute non-biliary pancreatitis is still unclear. AIM: The purpose of this study was to evaluate the function of the sphincter of Oddi (SO) and the effect of somatostatin on patients with non-biliary pancreatitis. METHODS: Twenty patients (18 males, two females) with acute pancreatitis (alcoholic 18, idiopathic two) received SO manometry within one week after admission. After baseline measurement, a bolus dose of somatostatin (Stilamin, Serono) 250 microg was infused slowly, and SO manometry was repeated after five minutes. Continuous infusion of somatostatin 250 microg/h was given for 12 hours after SO manometry. Serum amylase, lipase, glucose, and C reactive protein (CRP) levels were examined before and after somatostatin infusion. RESULTS: SO manometry was unsuccessful in six patients due to contracted sphincter. In the remaining 14 patients, high SO basal pressure (SOBP >40 mm Hg) was found in seven patients. After somatostatin infusion, mean SOBP decreased from 48.8 (29) to 31.9 (22) mm Hg (p<0.01). One patient had a paradoxical reaction to somatostatin (SOBP increased from 30 to 50 mm Hg) while the other 13 patients had a fall in SOBP after somatostatin. One patient developed abdominal pain with a serum amylase level of 2516 IU/l after SO manometry. No other side effects or changes in amylase, lipase, glucose, or CRP levels were observed in the other 19 patients after SO manometry and somatostatin infusion. DISCUSSION: Sphincter of Oddi dysfunction is common in patients with acute non-biliary pancreatitis and in most cases somatostatin can relax the sphincter.

Acute Disease↗

PubMed2001

Influence of acupuncture upon expressing levels of basic fibroblast growth factor in rat brain following focal cerebral ischemia--evaluated by time-resolved fluorescence immunoassay.

We investigate the expression of basic fibroblast growth factor (bFGF) during ischemia-reperfusion with or without electroacupuncture (EA) treatment, and observe the effect of EA on ischemic cerebral injury. In the present study, a sensitive sandwich time-resolved fluoroimmunoassay (TR-FIA) method was developed to quantitatively analyze the levels of bFGF in rat brain. The results indicated that the obvious cerebral infarction and swelling were observed after ischemia-reperfusion, and the opening amount of cerebral blood micrangium was increased. In the meantime, the expression of bFGF was also improved in striatum and frontoparietal cortex. EA alleviated the ischemic injuries induced by MCAO and markedly upregulated the opening amount of the micrangium. Owing to application of EA, the expression of bFGF was notably enhanced in striatum and cortex. The results give us some hints for the neuroprotective mechanism of EA, that is, EA may partially exert protective effects on neurons through regulating the blood dynamics and the endogenous expression of bFGF.

Animals↗

PubMed2001

Effects of the antianginal drug fendiline on Ca2+ movement in hepatoma cells.

This study investigated the effect of the anti-anginal drug, fendiline, on intracellular free Ca2+ levels ([Ca2+]i) in HA/ 22 human hepatoma cells by using fura-2 as a fluorescent Ca2+ dye. Fendiline (1-100 microM) increased [Ca2+]i with an EC50 of 25 microM. Removal of extracellular Ca2+ reduced the [Ca2+]i signals by 51 +/- 5%. Fendiline (10 microM)-induced Ca2+ release was abolished by pretreatment with 1 microM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor). Inhibition of phospholipase C with 2 microM 1-(6-((17beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione (U73122) did not alter 10 microM fendiline-induced Ca2+ release. Several other calmodulin antagonists, such as phenoxybenzamine (100-200 microM), trifluoperazine (5-50 microM), and fluphenazine-N-chloroethane (2-100 microM), had no effect on [Ca2+]i. Together, it was found that fendiline increased [Ca2+]i in human hepatoma cells by discharging Ca2+ from the endoplasmic reticulum in an inositol 1,4,5-trisphosphate-independent manner and by inducing Ca2+ entry. This effect of fendiline does not appear to be via antagonism of calmodulin.

Calcium↗

PubMed2001

Melatonin might be one possible medium of electroacupuncture anti-seizures.

To explore the alteration of melatonin (MT) levels in pineal, hippocampus and serum during seizure crises and electroacupuncture (EA) anti-seizures, we established a rat seizure model by microinjecting benzylpenicillin into hippocampus. EA was performed on "Fengu" (DU 16) and "Jinsuo" (DU 8) acupoints in rats. Electroencephalogram (EEG) of rats was recorded and the relative power (RP) of 1 approximately 30 HZ band of EEG was analyzed. A capillary electrophoresis-electrochemical detection method was used to determine MT contents. Our results indicated that MT level was elevated in pineal and hippocampus, and first had no change then significantly evaluated in serum during seizure crisis. The elevation of MT level was greatly potentiated with 30 min EA treatment (P<0.05). Meanwhile, the degree of seizures and the increases of EEG RP induced by seizures were significantly reduced (P<0.05). Because MT was considered as an antistressor and a natural downregulator of epileptiform activity, we postulate that the elevation in MT level during seizures may be one endogenous mechanism that counteracts convulsions and seizure-induced stress. A further elevation of MT levels with EA treatment suggests that MT might be one of the possible mediums of EA anti-seizures.

Animals↗

PubMed2001

Cathepsin E and subtypes of intestinal metaplasia in carcinogenesis of the human stomach.

BACKGROUND: Cathepsin E is found mainly over the gastric surface and foveolar epithelial cells, and it also is found in the metaplastic pyloric glands and cancer cells. The exact function of cathepsin E in gastric mucosa remains unclear. The colonic type (type III) of intestinal metaplasia (IM) is strongly associated with intestinal-type gastric carcinoma. IM is considered to be a precancerous lesion. The aim of this study was to find out the role of cathepsin E in IM, dysplasia and cancer of stomach. METHODS: Sixty nine biopsy specimens with IM and dysplasia and 33 gastrectomy specimens with gastric carcinoma were fixed, sectioned and stained with PAS-alcian blue stain, high iron-diamine alcian blue stain to classify IM and immunohistochemical stain to localize cathepsin E. Those patients with dysplastic gastric lesions received regular endoscopic follow-up. RESULTS: Fifteen of 69 patients with gastric dysplasia developed cancer in a median 10.5 months follow-up. Severe dysplasia developed carcinoma significantly higher than mild dysplasia (12/20 vs. 1/25, p < 0.001), and type III intestinal metaplasia seemed to have significantly predilection for severe dysplasia and gastric cancer. Cathepsin E was stained in intestinal metaplasia with dysplastic change in 44/69 specimens (63.8%), and carcinoma in 28/48 (58.3%) specimens, there was no significant difference between intestinal type and diffuse type carcinoma in cathepsin E staining. The positive staining for cathepsin E decreased significantly in severe dysplastic gastric mucosa. CONCLUSIONS: Type III IM is commonly associated with severe dysplasia and cancer; it may be a precancerous lesion. The positive staining of cathepsin E decreased with the severity of gastric dysplasia, representing dedifferentiation of the cells.

Aged↗

PubMed2001

Follow-up of Helicobacter pylori status by using 13C-urea breath test in nonulcer dyspeptic patients after eradication therapy.

BACKGROUND: The role of eradication therapy is still controversial in H. pylori-related nonulcer dyspepsia (NUD). The aim of this study was to follow up the H. pylori status after eradication therapy in patients with NUD by using l3C-urea breath test (UBT). METHODS: Patients with a clinical and endoscopic diagnosis of NUD were included. H. pylori infection was established by endoscopic biopsies and 13C-UBT. Patients with H. pylori infection then received a quadruple therapy with colloidal bismuth subcitrate, metronidazole, tetracycline and lansoprazole. Two months after completion of therapy, endoscopic biopsies and 13C-UBT were performed again to confirm eradication. A follow-up 13C-UBT was carried out again in one year to detect recurrence of H. pylori infection. RESULTS: Eighty-eight of the 148 patients (59.5%) were found to have H. pylori infection by both endoscopic biopsies and 13C-UBT. Anti-H. pylori therapy was given for 55 patients and proved successful in 33 of them two months after the end of therapy. However, recurrence was found one year later in three of these 33 cases, making a recurrence rate of 9.1% (3/33). Three of the 22 cases with unsuccessful eradication were found to have H. pylori eradication at one year by follow-up 13C-UBT. One of the 33 H. pylori-positive patients without anti-H. pylori therapy, who had negative 13C-UBT in one year follow-up, was found taking a high dose and long period of antibiotics. CONCLUSIONS: The recurrence rate of H. pylori infection in our study was higher than that in the Western population. Delayed eradication of H. pylori may occur after anti-H. pylori therapy. Spontaneous eradication is rare in patients not receiving anti-H. pylori eradication.

Breath Tests↗

PubMed2000

Histamine-Induced increases in intracellular free Ca2+ levels in hepatoma cells.

The effect of histamine on intracellular free Ca2+ levels ([Ca2+]i) in HA22/VGH human hepatoma cells were evaluated using fura-2 as a fluorescent Ca2+ dye. Histamine (0.2-5 microM) increased [Ca2+]i in a concentration-dependent manner with an EC50 value of about 1 microM. The [Ca2+]i response comprised an initial rise, a slow decay, and a sustained phase. Extracellular Ca2+ removal inhibited 50% of the [Ca2+]i signal. In Ca2+-free medium, after cells were treated with 1 microM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor), 5 microM histamine failed to increase [Ca2+]i. After pretreatment with 5 microM histamine in Ca2+-free medium for 4 min, addition of 3 mM Ca2+ induced a [Ca2+]i increase of a magnitude 7-fold greater than control. Histamine (5 microM)-induced intracellular Ca2+ release was abolished by inhibiting phospholipase C with 2 microM 1-(6-((17beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione (U73122), and by 5 microM pyrilamine but was not altered by 50 microM cimetidine. Together, this study shows that histamine induced [Ca2+]i increases in human hepatoma cells by stimulating H1, but not H2, histamine receptors. The [Ca2+]i signal was caused by Ca2+ release from thapsigargin-sensitive endoplasmic reticulum in an inositol 1,4,5-trisphosphate-dependent manner, accompanied by Ca2+ entry.

Biological Transport↗

PubMed2000

Effect of betulinic acid on intracellular-free Ca(2+) levels in Madin Darby canine kidney cells.

The effect of betulinic acid, an anti-tumor and apoptosis-inducing natural product, on intracellular-free levels of Ca(2+) ([Ca(2+)](i)) in Madin Darby canine kidney (MDCK) cells was examined by using fura-2 as a Ca(2+) dye. Betulinic acid caused significant increases in [Ca(2+)](i) concentration dependently between 25 and 500 nM with an EC(50) of 100 nM. The [Ca(2+)](i) signal was composed of an initial gradual rise and a plateau. The response was decreased by removal of extracellular Ca(2+) by 45+/-10%. In Ca(2+)-free medium, pretreatment with 1 microM thapsigargin (an endoplasmic reticulum Ca(2+) pump inhibitor) abolished 250 microM betulinic acid-induced [Ca(2+)](i) increases. Conversely, pretreatment with betulinic acid only partly inhibited thapsigargin-induced [Ca(2+)](i) increases. Addition of 3 mM Ca(2+) induced a [Ca(2+)](i) increase after pretreatment with 250 nM betulinic acid in Ca(2+)-free medium for 5 min. This [Ca(2+)](i) increase was not altered by the addition of 20 microM SKF96365 and 10 microM econazole. Inhibiting inositol 1,4,5-trisphosphate formation with the phospholipase C inhibitor U73122 (2 microM) abolished 250 nM betulinic acid-induced Ca(2+) release. Pretreatment with 10 microM La(3+) inhibited 250 nM betulinic acid-induced [Ca(2+)](i) increases by 85+/-3%; whereas 10 microM of verapamil, nifedipine and diltiazem had no effect. In Ca(2+) medium, pretreatment with 2.5 nM betulinic aid for 260 s potentiated 10 microM ATP and 1 microM thapsigargin-induced [Ca(2+)](i) increases by 33+/-3% and 45+/-3%, respectively. Trypan blue exclusion revealed that acute exposure of 250 nM betulinic acid for 2-30 min decreased cell viability by 6+/-2%, which could be prevented by pretreatment with 2 microM U731222. Together, the results suggest that betulinic acid induced significant [Ca(2+)](i) increases in MDCK cells in a concentration-dependent manner, and also induced mild cell death. The [Ca(2+)](i) signal was contributed by an inositol 1,4, 5-trisphosphate-dependent release of intracellular Ca(2+) from thapsigargin-sensitive stores, and by inducing Ca(2+) entry from extracellular medium in a La(3+)-sensitive manner.

Adenosine Triphosphate↗

PubMed2000

Dual effect of tamoxifen, an anti-breast-cancer drug, on intracellular Ca(2+) and cytotoxicity in intact cells.

The effect of tamoxifen on Ca(2+) signaling and viability in Madin Darby canine kidney (MDCK) cells was investigated by using fura-2 as a Ca(2+) probe. Tamoxifen evoked a rise in cytosolic free Ca(2+) levels ([Ca(2+)](i)) concentration-dependently between 1 and 50 microM with an EC50 of 10 microM. The response was decreased by extracellular Ca(2+) removal. In Ca(2+)-free medium, pretreatment with 5 microM tamoxifen abolished the [Ca(2+)](i) increase induced by the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin (1 microM), but pretreatment with brefeldin A (50 microM; a Ca(2+) mobilizer of the Golgi complex), thapsigargin (an inhibitor of the endoplasmic reticulum Ca(2+) pump), and carbonylcyanide m-chlorophenylhydrazone (CCCP; a mitochondrial uncoupler), only partly inhibited tamoxifen-induced [Ca(2+)](i) increases. This suggests that tamoxifen released Ca(2+) from multiple pools. Addition of 3 mM Ca(2+) induced a [Ca(2+)](i) rise after pretreatment with 5 microM tamoxifen in Ca(2+)-free medium. Inhibiting inositol 1,4,5-trisphosphate formation with the phospholipase C inhibitor U73122 (2 microM) did not alter 5 microM tamoxifen-induced Ca(2+) release. The [Ca(2+)](i) increase induced by 5 microM tamoxifen was not altered by La(3+), nifedipine, verapamil, or diltiazem. Tamoxifen (1-10 microM) decreased cell viability in a concentration- and time-dependent manner. Tamoxifen (5 microM) also increased [Ca(2+)](i) in neutrophils, bladder cancer cells, and prostate cancer cells from humans and glioma cells from rats. Collectively, it was found that tamoxifen increased [Ca(2+)](i) in MDCK cells by releasing Ca(2+) from multiple Ca(2+) stores in a manner independent of the production of inositol 1,4, 5-trisphosphate and also by triggering Ca(2+) influx from extracellular space. The [Ca(2+)](i) increase was accompanied by cytotoxicity.

Animals↗

PubMed2000

Chronic dizziness in older adults.

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Aged↗

PubMed2000

Effect of adenosine on adenosine triphosphate-sensitive potassium channel during hypoxia in rat hippocampal neurons.

Using the whole-cell patch clamp method, we explored the effect of adenosine on the K(ATP) current and its regulatory mechanisms in acutely dissociated rat hippocampal neurons. A chemical hypoxia model was made using 0.2 mmol/l 2,4dinitrophenol (2,4DNP). During hypoxia, the K(ATP) current was not raised significantly by adenosine alone, but was accelerated significantly by adenosine in combination with the selective A(2) receptor blocker 3, 7-dimethl-1-propargylxanth-ine. The selective A(1) receptor agonist N6-cyclopentyladenosine also accelerated the K(ATP) current. These results suggest that activation of the adenosine A(1) receptor can accelerate opening of the K(ATP) channel during hypoxia, and that the A(2) receptor may have an opposing effect to the A(1) receptor.

2,4-Dinitrophenol↗

PubMed2000

Ca(2+) mobilization induced by W-7 in MG63 human osteosarcoma cells.

The effect of N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride (W-7), a widely used calmodulin inhibitor, on intracellular free Ca(2+)levels ([Ca(2+)](i)) in MG63 human osteosarcoma cells was explored using fura-2 as a Ca(2+)probe. W-7 (20-1000 micro m) induced an increase in [Ca(2+)](i)in a dose-dependent manner, with an EC(50)of 100 microm. The [Ca(2+)](i)signal comprised an initial rise and a sustained plateau without significant decay within 5 min. External Ca(2+)removal decreased the Ca(2+)signals by reducing the peak and sustained phase, indicating W-7-activated intracellular Ca(2+)release and extracellular Ca(2+)influx. W-7 (500 microm) failed to induce a [Ca(2+)](i)increase in a Ca(2+)-free medium after pre-treatment with thapsigargin (1 microm), an endoplasmic reticulum Ca(2+)pump inhibitor. Conversely, W-7 pre-treatment abolished the Ca(2+)release induced by thapsigargin. This suggests that W-7 (500 microm ) released internal Ca(2+)mainly from the endoplasmic reticulum. The addition of 3 mm Ca(2+)increased [Ca(2+)](i)dose-dependently after preincubation with 20-1000 microm W-7 in a Ca(2+)-free medium, implying that W-7 induced capacitative Ca(2+)entry. W-7-induced Ca(2+)release was not altered by inhibiting phospholipase C with 2 microm 1-(6-((17 beta - 3-methoxyestra-1,3, 5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione) (U73122). Tryphan blue assay demonstrated that W-7 (200 microm) caused gradual cell death within 30 min of the initial drug exposure. Together, it was found that W-7 induced [Ca(2+)](i)increases in human osteosarcoma cells by releasing internal Ca(2+)from the endoplasmic reticulum, and also by triggering Ca(2+)influx. W-7 may be cytotoxic to osteosarcoma cells.

Animals↗

PubMed2000

Dual action of palmitoyl trifluoromethyl ketone (PACOCF3) on Ca2+ signaling: activation of extracellular Ca2+ influx and alteration of ATP- and bradykinin-induced Ca2+ responses in Madin Darby canine kidney cells.

The effect of the phospholipase A2 inhibitor palmitoyl trifluoromethyl ketone (PACOCF3) on Ca2+ signaling in Madin Darby canine kidney (MDCK) cells was examined using fura-2 as the fluorescent Ca2+ indicator. At a concentration of 20 microM, PACOCF3 did not change basal cytosolic free calcium concentrations ([Ca2+]i), but at concentrations of 50-250 microM PACOCF3 induced an increase in [Ca2+]i by activating extracellular Ca2+ entry which was partly suppressed by 50 microM La3+. The effect of PACOCF3 was abolished by removal of extracellular Ca2+. PACOCF3 (10 microM) enhanced both the peak value and the area under the curve of the [Ca2+]i increase induced by 10 microM ATP and 1 microM bradykinin by potentiating extracellular Ca2+ influx without affecting internal Ca2+ release. Several other phospholipase A2 inhibitors had no effect on basal [Ca2+]i or agonist-induced [Ca2+]i increases. Collectively, the results suggest that PACOCF3 alters Ca2+ signaling in renal tubular cells in a manner independent of phospholipase A2 inhibition.

Adenosine Triphosphate↗

PubMed2000

NPC-14686, a novel anti-inflammatory agent, increased intracellular Ca(2+) concentrations in MDCK renal tubular cells.

The effect of NPC-14686 (Fmoc-L-homophenylalanine), a novel anti-inflammatory agent on intracellular free Ca(2+) concentrations ([Ca(2+)](i)) in Madin Darby canine kidney (MDCK) renal tubular cells, was investigated, using fura-2 as a Ca(2+) dye. At concentrations between 10 and 200 microM NPC-14686 increased [Ca(2+)](i) concentration dependently. The [Ca(2+)](i) signal comprised an initial rise and a sustained phase. Ca(2+) removal inhibited the Ca(2+) signals by 90%. In Ca(2+)-free medium, pretreatment with 100 microM NPC-14686 nearly abolished the [Ca(2+)](i) increase induced by 1 microM thapsigargin (an endoplasmic reticulum Ca(2+) pump inhibitor) and abolished the [Ca(2+)](i) increase induced by 2 microM carbonylcyanide m-chlorophenylhydrazone (CCCP) (a mitochondrial uncoupler). NPC-14686 (100 microM) induced a slight [Ca(2+)](i) increase after pretreatment with 2 microM CCCP and 1 microM thapsigargin. Addition of 3 mM Ca(2+) elicited a [Ca(2+)](i) increase in cells pretreated with 100 microM NPC-14686 in Ca(2+)-free medium. Inhibition of inositol-1,4,5-trisphosphate (IP(3)) production by suppressing phospholipase C with 2 microM U73122 did not alter NPC-14686-induced Ca(2+) release. Trypan blue exclusion revealed that incubation with 10 or 200 microM NPC-14686 for 1-30 min decreased cell viability by 10-20% concentration dependently. Collectively, the results demonstrate that, in MDCK tubular cells, NPC-14686 induced Ca(2+) release followed by Ca(2+) entry, with the latter playing a major role. NPC-14686 appears to release intracellular Ca(2+) in an IP(3)-uncoupled manner. NPC-14686 may be of mild cytotoxicity.

Aminobutyrates↗