ISSN:0012-2823    

DOI:10.1159/000201512

出版商:S. Karger AG    

年代:1997

数据来源: Karger

ISSN:0012-2823    

DOI:10.1159/000201513

出版商:S. Karger AG    

年代:1997

数据来源: Karger

ISSN:0012-2823    

DOI:10.1159/000201514

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Cell isolation may impair secretory chief cell functions. To evaluate whether a monolayer culture results in a recovery, we compared the effects of cholecystokinin (CCK) octapeptide (CCK-8) on pepsinogen release from freshly isolated and from cultured porcine chief cells. CCK-8 had no significant effect on freshly isolated porcine chief cells but stimulated pepsinogen release from 36-and 60-hour cultured cells with EC50 values of 180 and 130 nmol/l, respectively. Maximal stimulation, achieved at a concentration of 1 μmol/l, amounted to 289 ± 63 (p < 0.01) and 401 ± 64% (p < 0.01) of the respective control value. In addition, the CCK-8 concentration-response curve for 60-hour, but not for 36-hour cultured chief cells displayed a second stimulatory peak at a CCK-8 concentration of 100 pmol/l (266 ± 55% of control value, p < 0.05) with an EC50 value of 16 pmol/l. The CCKA-receptor antagonist devazepide (10 nmol/l) prevented the stimulatory effect of 1 μmol/l CCK-8 on pepsinogen release of 60-hour cultured cells. The adenylate cyclase activator forskolin (10 μmol/l) potentiated the low concentration CCK-8 effect, shifting the peak stimulation to a CCK-8 concentration of 10pmol/l, and inhibited the high concentration CCK-8 effect on 60-hour cultured cells. These results indicate a time-dependent recovery of the CCK response of porcine gastric chief cells in monolayer culture and suggest that this model has an advantage over freshly isolated chief cells with regard to the pharmacological characterization of CCK ef

ISSN:0012-2823    

DOI:10.1159/000201418

出版商:S. Karger AG    

年代:1997

数据来源: Karger

ISSN:0012-2823    

DOI:10.1159/000201516

出版商:S. Karger AG    

年代:1997

数据来源: Karger

ISSN:0012-2823    

DOI:10.1159/000201517

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The role of nitric oxide (NO) in the gastric mucosal blood flow response and the healing of HCl-induced gastric lesions was investigated in rats. After 18 h fasting rats were given 0.6 N HCl p.o. for the induction of gastric lesions, and 1 h later they were fed normally. After induction of gastric lesions, they were repeatedly administered the NO synthase inhibitors NG-nitro-L-arginine methyl ester (L-NAME 5-20 mg/kg p.o. twice daily) or aminoguanidine (20 mg/kg s.c. once daily) for 7 days. Gastric lesions caused by HCl healed almost completely within 5 days with granulation and to an extent with re-epithelialization. Repeated administration of L-NAME but not aminoguanidine significantly delayed the healing of gastric lesions in a dose-dependent manner. The damaged mucosa secreted less acid, but showed a marked rise in H+ permeability, resulting in luminal acid loss accompanied by an increase of mucosal blood flow. Aminoguanidine did not significantly affect any of these functional changes observed in the stomach after damage by HCl, whereas L-NAME treatment slightly reversed the decreased acid response, increased the luminal H+ loss, and totally inhibited the mucosal hyperemic response associated with luminal acid loss in the damaged mucosa. In addition, the deleterious influences of L-NAME on the mucosal blood flow response and the healing of gastric lesions were significantly antagonized by co-administration of L-arginine but not of D-arginine (500 mg/kg × 2, i.p.). Luminal output ofNO-2/NO-3 was significantly increased in pylorus-ligated stomachs in control rats on days 3 and 5 after damage, and such increases in gastric NO output were completely attenuated by L-NAME treatment. These results suggest that endogenous NO may contribute to the healing of acute gastric injury by mediating the mucosal hyperemic responses associated with acid back-diffusion and by facilitating acid disposal in the damaged mucosa. NO mediating such responses and participating in the healing aspect of gastric lesions may be produced by the constitutive type of NO synthase

ISSN:0012-2823    

DOI:10.1159/000201419

出版商:S. Karger AG    

年代:1997

数据来源: Karger

ISSN:0012-2823    

DOI:10.1159/000201518

出版商:S. Karger AG    

年代:1997

数据来源: Karger

ISSN:0012-2823    

DOI:10.1159/000201519

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The mechanism of regulation of mucus production in the gastric mucosa remains unclear. Recently, we established a gastric surface mucous cell line GSM06, which produces periodic acid-Shiff (PAS)-positive glycoconjugate (mucus) layers on the cell surface, from transgenic mice harboring a temperature-sensitive simian virus 40 large T-antigen gene. In this study, GSM06 cells were examined for its production of PAS-positive glycoconjugate layers to acid secretagogues and growth factors. The cells were cultured at nonpermissive temperature (39°C) for 3-18 days and stained with PAS. Insulin (1-30 μg/ml; 0.29-8.6 μM) time- and dose-dependently increased production of glycoconjugates on the cell surface. When glycoconjugate layers produced by stimulation of insulin (3-30 μg/ml; 0.86-8.6 μM) were removed from the cell surface of GSM06 cells by a mild trypsin treatment, PAS-positive materials were remarkably decreased (day 18). In addition, morphological findings indicate that a high concentration of insulin (30 μg/ml; 8.6 μM) produced thick PAS-positive glycoconjugate layers just like normal gastric surface mucosa on the cell surface on day 18. In contrast, histamine (0.1-100 μM), carbachol (0.1-100 μM), gastrin-17 (0.1-100nM), epidermal growth factor (0.01-10 ng/ ml; 1.7-1,700 pM), transforming growth factor-α (0.01-10 ng/ml; 1.8-1,800 pM), and fetal bovine serum (1-10%) did not increase glycoconjugate production. These findings suggest that insulin is a stimulator of glycoconjugate production, and stimulates production of glycoconjugate layers on the cell surface in the gastric surface mucous cell l

ISSN:0012-2823    

DOI:10.1159/000201420

出版商:S. Karger AG    

年代:1997

数据来源: Karger