首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献,搜索用时 31 毫秒
1.
The effect of oral prostaglandin E2 (PGE2) on gastric acid secretion was examined in healthy subjects. The gastric secretion was stimulated by a modified shamfeeding procedure. Each subject underwent one control test and three tests with intragastrically administered graded doses of PGE2: 0.5, 1.0 and 2.0 mg. Oral PGE2 significantly suppressed the peak and total acid response to vagal stimulation. The total acid output in controls was 27.5 +/- 3.2 mmol/90 min and 20.8 +/- 2.8, 15.8 +/- 2.2 (p less than 0.01) and 15.9 +/- 3.8 (p less than 0.005) mmol/90 min in test series with 0.5, 1.0 and 2.0 mg PGE2 respectively. The two higher doses were equally inhibitory to an average 40%. Gastric outputs of sodium and potassium in response to modified shamfeeding were reduced by PGE2. In controls there was a significant release of plasma-gastrin in response to shamfeeding. Plasma-gastrin was apparently suppressed after the two lower doses of PGE2 but 2.0 mg PGE2 gave an elevation similar to controls. Thus the study demonstrates that oral natural PGE2 suppresses the gastric acid secretion in man. The absence of such an effect in prior studies has been one of the objections against an acid regulatory action of endogenously formed prostaglandins. The present results do not support this argument.  相似文献   

2.
This study investigated the action of enprostil, a synthetic analog of PGE2, on gastric HCO3 secretion in humans and on duodenal HCO3 secretion in the anesthetized rat. A previously validated 2-component model was used to calculate gastric HCO3 and H+ secretion in 10 human subjects. Compared to placebo, a single 70 μg oral dose of enprostil increased basal gastric HCO3 secretion from 1810 +- 340 to 3190 ± 890 μmol/hr (P < 0.05). In addition, enprostil reduced basal gastric H+ secretion from 5240 ± 1140 to 1680 ± 530 μmol/hr (P < 0.02). Enprostil also increased HCO3 and reduced H+ secretion during intravenous pentagastrin infusion. In the rat, duodenal HCO3 secretion was measured by direct titration in situ using perfused segments of duodenum just distal to the Brunner gland area dn devoid of pancreatic and biliary secretions. Addition of enprostil(10 μg/ml) to the duodenal bathing solution increased duodenal HOC3 secretion from 6.3 ± 1.3 to 15.1 ± 2.0 μmol/cm·hr (P < 0.01, n = 6). The stimulatory action of enprostil on duodenal HCO3 secretion at 10 μg/ml was comparable in magnitude and duration to that of 10 μg/ml natural PGE2. In summary, the PGE2 analog enprostil stimulated gastroduodenal HCO3 secretion, effects which may be beneficial in protection of the gastroduodenal mucosa against luminal acid.  相似文献   

3.
The influence of transposing the C-15 hydroxy group of prostaglandin E1 methyl ester (PGE1ME) on gastric antisecretory and antiulcer actions was investigated. The compound (±)15-deoxy- 16α,β-hydroxy PGE1ME (SC-28904) was equipotent to the reference standard PGE1ME in suppressing histamine-stimulated gastric secretion in the Heidenhain pouch (HP) dog. In contrast to PGE1ME, SC-28904 was longer acting when administered intravenously and also showed significant oral activity in the histamine-stimulated gastric fistula dog. SC-28904 was also equipotent to PGE1ME (range of active doses of 0.5 to 5.0 mg/kg, s.c.) in inhibiting forced-exertion gastric ulceration in rats.The compound (±)15-deoxy-17α,β-hydroxy PGE1ME (SC-30693) was an inactive antisecretory agent in the dog at the 1.0 mg/kg i.v. bolus dose. This dose was 100 times greater than the active antisecretory dose of PGE1ME. Likewise, SC-30693, when administered subcutaneously at a 5.0 mg/kg dose, was also totally inactive in preventing gastric ulcers induced by forced exertion in rats.The important implications of this work are that some of the receptor sites for the PGE1 molecule could easily accommodate the side chain hydroxy group either in the C-15 or C-16 position. Moreover, the hydroxy group in the latter position significantly improved the biological activity of PGE1ME.  相似文献   

4.
Filling of the gastric lumen of rats with 1.0 M NaCl solution (5 ml) for 10 min under urethane anesthesia caused an increase in the gastric fluid concentrations of prostaglandin (PG) E2, 13, 14-dihydro-15-keto-PGE2 and 6-keto-PGF as determined by radioimmunoassay. PGE2 was the major PG generated. The levels of PGE2 in the gastric fluid were increased dose-dependently after filling the lumen with 0.3, 0.5, 0.7 or 1.0 M NaCl solutions. The pH of the gastric fluid increased similarly after 0.5 to 1.0 M NaCl solutions. Indomethacin (10 mg/kg, i.p.) suppressed the PGE2 increase caused by 1.0 M NaCl solution, but did not prevent the increase of the pH of the gastric fluid induced by intragastric 1.0 M NaCl. Infusion of tetragastrin (62.5 μg/kg/hr, i.v., for 10 min) caused a marked increase of acid secretion without modifying intragastic concentration of PGE2. The acid secretion due to tetragastrin was completely inhibited after intragastric administration of 1.0 M NaCl solution, while indomethacin restored the tetragastrin-induced acid secretion, with prevention of a rise of intragastric PGE2 levels. These observations suggest that 1.0 M NaCl solutions suppress basal intragastric acid through a mechanism which is independent of prostaglandins. In contrast, the suppression of tetragastrin-induced acid secretion by intragastric 1.0 M NaCl solution appears to be mediated through a release of prostaglandins  相似文献   

5.
To study the influence of dietary modification on prostaglandin synthesis and on blood pressure regulation, the effects of dietary enrichment with linolenic or linoleic acid was compared with standard rat chow in 3 groups of 13 rats before and after renal artery constriction and contralateral nephrectomy. Before renal artery constriction 4 weeks supplementation with 40 en% linseed oil (53% linolenic acid) increased renal linolenic acid, decreased arachidonic acid, and suppressed synthesis of 6-keto-PGF and PGE2 by renal homogenates (33% and 38% respectively, p<0.01) compared with standard diet. Rats fed on 40 en % sunflower seed oil (63% linoleic acid) increased renal prostaglandin synthesis (p<0.05) compared with linseed oil, but not compared with standard diet. Seven weeks after renal artery constriction renal and aortic 6-keto-PGF and PGE2 were suppressed 30% to 50% (p<0.05) by linseed oil supplements compared with sunflower seed oil and standard diets. In the sunflower seed oil group aortic 6-keto-PGF correlated (r = 0.75, p<0.02) with final systolic blood pressure. Final systolic blood pressures were similar in linseed oil (152.9 mmHg ± se 3.3, sunflower oil (155.1 ± se 6.6) and standard diet group (159.0 ±se 4.2). Thus dietary linseed oil suppressed renal and aortic prostaglandin synthesis but did not accentuate renal hypertension, and linoleic acid supplementation did not protect against 1 kidney 1 clip renal hypertension.  相似文献   

6.
Bombesin, acetylcholine, prostaglandins and somatostatin are all thought to be involved in the regulation of gastrin release and gastric secretion. We have studied the effects of low doses of atropine, 16-16(Me)2-prostaglandin E2 (PGE2) and somatostatin-14 on bombesin-stimulated gastrin release and gastric acid and pepsin secretion in conscious fistula dogs. For reference, synthetic gastrin G-17 was studied with and without somatostatin. Bombesin, in a dose-related manner, increased serum gastrin, which in turn stimulated gastric acid and pepsin secretion in a serum gastrin, concentration-dependent manner. Somatostatin inhibited gastrin release by bombesin as well as the secretory stimulation by G-17; the combination of sequential effects resulted in a marked inhibition of bombesin-stimulated gastric acid and pepsin secretion. PGE2 also strongly inhibited gastrin release and acid and pepsin secretion. Atropine had no significant effect on gastrin release, but greatly inhibited gastric secretion. Thus somatostatin and PGE2 inhibited at two sites, gastrin release and gastrin effects, while atropine affected only the latter.  相似文献   

7.
The action of prostaglandins and indomethacin on gastric mucosal cyclic nucleotide concentrations was evaluated in 18 anesthetized mongrel dogs. Prostaglandins E1 (PGE1) and E2 (PGE2) (25 μg/kg bolus, then 2 μg/kg/min) were administered both intravenously (4 experiments; femoral vein) and directly into the gastric mucosal circulation (10 experiments; superior mesenteric artery). The possible synergistic effect of pre-treatment and continuous arterial infusion of indomethacin (5 mg/kg bolus for 5 min, then 5 mg/min), a prostaglandin synthetase inhibitor, with PGE2 was studied in 4 experiments. Antral and fundic mucosa were biopsied and measured by radioimmunoassay for cyclic nucleotides. Doses of PGE1 and PGE2 which inhibited histamine-stimulated canine gastric acid secretion did not significantly alter antral or fundic mucosal cyclic nucleotide concentrations. Concomitant infusion of PGE2 with indomethacin did not potentiate the mucosal nucleotide response compared to PGE2 alone. These studies fail to implicate cyclic nucleotides as mediators of the inhibitory acid response induced by PGE1 or PGE2 in intact dog stomach.  相似文献   

8.
The gastric antisecretory actions of (15S)-15-methyl prostaglandin E2 methyl ester (Me-PGE2) and Prostaglandin E2 (PGE2) were evaluated in the unanesthetized gastric fistula rhesus monkey. Secretion was submaximally stimulated by multiple subcutaneous injections of histamine acid phosphate given every hour for four consecutive hours. When a steady-state plateau of gastric secretion was reached, the PG's were administered as a single bolus dose either intravenously (i.v.) or intragastrically (i.g.). Both PG's inhibited histamine-stimulated gastric secretion. The PG's showed greater sensitivity in inhibiting acid concentration while not affecting volume output. Active i.v. and i.g. antisecretory doses of Me-PGE2 ranged from 3 to 10 μg/kg, while PGE2 showed significant antisecretory activity at i.v. bolus doses of 30–100 μg/kg and i.g. bolus dose of 1.0 mg/kg. Thus, Me-PGE2 is estimated to be at least 10 and 300 times more potent than PGE2 by the i.v. and i.g. administration routes, respectively. These findings indicate that the rhesus monkey shows some similarities to man in responsiveness to gastric secretory inhibition by E-prostaglandins.  相似文献   

9.
The presence of prostaglandins (PGs) was determined in gastric juice obtained from 3 conscious dogs, provided with a chronic gastric fistula. Outputs of acid (mequiv min?1) and PGs (pg min?1) were measured in gastric secretions stimulated by pentagastrin (100 or 200 ng kg?1min?1). Prostaglandin activity was estimated, after extraction and thin layer chromatography, by radioimmuno-assay of the PGB formed by treatment with alkali. Tritiated PGs were added to gastric juice for the purpose of correcting for PGs recovery. Using this method, the minimum mass of PGB which could be satisfactorily distinguished from zero was 25 pg. Prostaglandins A2 and E2 were present in pentagastrin-activated gastric secretions and averaged (mean ± SE, n = 8) 200.7 ± 18.1 and 260.1 ± 18.0 pg min?1 respectively. The identity of PGA2 and PGE2 was confirmed by gas liquid chromatography combined with mass spectrometry. The amount of PGE2 converted to PGA2 during extraction, separation and conversion procedures was estimated from the amount of [3H] PGA2 found when only [3H] PGE2 had been added to a sample of gastric juice and averaged 14.5% ± 2.0. Our preliminary results support the possibility that PGE2 and PGA2 may be of physiological importance in the regulation of canine gastric secretions.  相似文献   

10.
In gastrointestinal research the in vitro release of prostaglandins from incubated or cultured biopsies is a widely used method to estimate prostaglandin synthesis. We therefore investigated the rate limiting mechanisms of PGE2 release in organ cultured gastric mucosa of the rabbit, determining PGE2 secretion from organ cultured mucosal biopsies by radioimmunoassay and prostaglandin synthesizing capacity by in vitro incubation of mucosal homogenate or microsomes with [14C]-arachidonic acid.Freshly taken biopsies secreted PGE2 at an initial high rate, that decreased during the following 4 hrs of culture. This PGE2 release was dose dependently reduced by inhibitors of the prostaglandin cyclooxygenase. 5mM acetylsalicylic acid (ASA) maximally suppressed PGE2 secretion to 7% of controls, and the inhibition by ASA was quantitatively similar at every given culture period. PGE2 release was markedly increased by carbenoxolone but was only slightly activated by extracellular calcium and the Ca++-ionophore A23187. However, Ca++/A23187 were unable to maintain PGE2 secretion at the initial rate.PGE2 secretion was undisturbed in calcium-free medium but was reduced to 50–60% of controls by excess EDTA. The intracellular calcium chelator 1,2-bis-(2-aminophenoxy)-ethane-N,N,N′,N′,-tetraacetic acid-acetoxymethyl ester (BAPTA-AM) similarly inhibited PGE2 release to 72% of controls. In contrast, PGE2 release was unaffected by the intracellular calcium antagonist 3,4,5-trimethylene-bis(4-formylpyridinium bromide) dioxime (TMB-8), the calmodulin antagonists N-(6-aminohexyl)-1-5-chloro-1-naphthalenesulfonamide (W-7) and calmidazolium (compound R24571) or various direct inhibitors of endogenous arachidonic acid release like tetracaine, bromophenacyl bromid, neomycine or low dose quinacrine, indicating that the reduction of PGE2 release by EDTA or BAPTA may be mediated by mechanisms different from substrate release. In contrast, an inhibition of PGE2 secretion by quinacrine at high concentrations (≥ 0.8mM) was attributed to a direct inhibition of the prostaglandin cyclooxygenase, similar to ASA. Finally, the reduction of the prostaglandin synthesizing capacity by ASA was strongly correlated with the inhibition of PGE2 secretion, also at low concentrations and minor degrees of inhibition.From these data we conclude, that the activity of the prostaglandin cyclooxygenase is rate limiting for PGE2 secretion from organ cultured mucosal biopsies rather than arachidonic acid release by a phospholipase A2. This should be considered for interpretation of studies based on prostaglandin release from cultured mucosa.  相似文献   

11.
The effects of orally administered prostaglandin E2, 16,16-dimethyl prostaglandin E2 and U-46619, an analogue of the prostaglandin endoperoxide PGH2, on gastric secretory volume, acid and mucus were studied in the rat. All of the compounds significantly increased the volume of gastric secretion, mucus secretion, measured as N-acetylneuraminic acid and mucus synthesis measured as the incorporation of [3H]-glucosamine into mucosal glycoprotein; however, only PGE2 and 16,16-dimethyl PGE2 inhibited acid secretion. U-46619, 1.5 mg/kg provided significant protection against ethanol-induced gastric ulcers, an effect that has been previously shown for the other two compounds. These studies provide additional evidence that prostaglandin induced mucosal protection may by related to an effect on mucus and on stimulation of nonparietal cell gastric secretion. Further study of these parameters may be important in the development of antiulcer drugs for long term clinical use.  相似文献   

12.
Proton pump inhibitors (PPIs) are widely used to treat hyperacid secretion and stomach ulcers. The study investigated the anti-secretory and anti-ulcer effects of esomeprazole, the S-isomer of omeprazole on dimaprit, histamine and dibutyryl adenosine 3, 5 cyclic monophosphate (dbcAMP)-evoked gastric acid secretion, acidified ethanol (AE) and indomethacin (INDO)-induced haemorrhagic lesions and on prostaglandin E2 (PGE2) level in the rat in vivo and rabbit in vitro preparations. The effect of omeprazole was also investigated for comparison. Dimaprit-induced acid secretion was significantly (P < 0.05) inhibited by both PPIs in a dose-dependent manner. In the isolated rabbit gastric glands, both PPIs elicited marked reductions in histamine- and dbcAMP-evoked acid secretion with similar potency. The lesions induced by either AE or INDO were significantly (P < 0.05) reduced in the presence of either esomeprazole or omeprazole compared to control values. Increasing doses of esomeprazole before AE treatment resulted in a marked degree of cytoprotection and an elevation in the concentration of bound PGE2 in the stomach tissue homogenate. The results show that esomeprazole and omeprazole were equally effective against gastric haemorrhagic lesions induced by either AE or INDO and in inhibiting dimaprit-, dbcAMP- and histamine-induced gastric acid secretion in the rat and rabbit stomach both in vivo and in vitro. The gastro-protective effect of esomeprazole was found to be proportional to the bound PGE2 levels in the glandular area of the stomach.  相似文献   

13.
The effects of prostacyclin (PGI2) and its breakdown product 6-oxo-PGF on various aspects of gastric function were investigated in the rat. PGI2 increased mucosal blood flow when infused intravenously. PGI2 was a more potent inhibitor of gastric acid secretion in vivo than PGE2. Like PGE2, PGI2 inhibited acid secretion from the rat stomach in vitro. PGI2 had comparable activity to PGE2 in inhibiting indomethacin-induced gastric erosions. Thus prostacyclin shares several of the activities of PGE2, and may be involved in the regulation of gastric mucosal function.  相似文献   

14.
Twelve patients with inactive ulcer disease were administered placebo and ranitidine via bolus and continuous intravenous infusions, at doses ranging from 50 every 8 h, to 12.5 mg/h for 24 h. Gastric acid was collected for 20 min each h for 24 h, and ranitidine serum concentrations were measured ± every 2 h, during each of the six study periods. Cosinor analysis of gastric acid secretion during placebo treatment revealed a significant circadian rhythm in all subjects. Mesor acid output ranged from 1.7 to 11.6 mmol/h (mean 5.6 ± 2.8 mmol/h) and the amplitude ranged from 0.7 to 6.5 mmol/h (mean 2.8 ±1.6 mmol/h). Peak acid output (acrophase) occurred at 10 p.m. ± 3 h. A pharmacodynamic model, relating ranitidine serum concentration to hourly acid secretion, was derived, which incorporated the circadian change in basal acid output. Data for this fractional response model included basal acid secretion–as determined by time of day, measured acid secretion, and associated serum ranitidine concentration. The 50% inhibitory concentration (IC50) for ranitidine ranged from 10-75 ng/ml, with a mean of 44 ng/ml. The variation in IC50 and in basal acid secretion combined to produce a wide variation in the pharmacodynamic response to ranitidine. The model-predicted serum concentrations, required to maintain acid secretion at 0.1 mmol/h, ranged from 250 to 1550 ng/ml, at the time of peak evening acid secretion. Despite a constant degree of acid inhibition by ranitidine during the day, higher serum concentrations are required during times of peak acid output to maintain adequate suppression of hydrogen ion secretion.  相似文献   

15.
Normal conscious female Sprague-Dawley rats were treated with chlorazanil (3 mg/kg i.p.), and urine was collected for 3 hours. Urine prostaglandin E2-excretion increased from 25±3 to 271±32 ng/kg/3 h. The enhancement of urine PGE2-excretion was inhibited by pretreatment with bumetanide (75 mg/kg p.o.). In separate experiments the papillary quantity of PGE2 was determined in freshly homogenized tissue. The basal level (14±2 ng PGE2/papilla) was increased by chlorazanil to 51±11 ng PGE2/papilla and 24±7 ng PGE2/papilla at one and two hours respectively after drug administration. The capacity of chlorazanil to increase medullary PGE2 accumulation was unaffected by bumetanide dissociated the medullary PGE2 level from the excretion of PGE2 in urine, when the former was elevated by chlorazanil.  相似文献   

16.
The effects of Prostacyclin (PGI2) infusion on insulin secretion and glucose tolerance were investigated in 7 healthy subjects. PGI2 infusion caused no statistically significant changes of either glucose or insulin concentration, over the range 2.5–20 ng/Kg/min. A constant PGI2 infusion (10 ng/Kg/min) did not inhibit acute insulin responses to a glucose (20 g i.v.) pulse (response before PGI2 = 612±307%; during PGI2 = 515±468%, mean ± SD, mean change 3–5 min insulin, % basal; P=NS). Glucose disappearance rates were similar after the first and second glucose pulse.Thus, in contrast to PGE2, PGI2 does not affect insulin secretion nor glucose disposal at doses producing platelet and vascular changes. It is hypothesized that an altered PGI2/PGE2 balance in diabetes may represent a link between vascular, platelet and metabolic changes.  相似文献   

17.
Oral prostaglandin E2 (PGE2) has specific protective effects so called cytoprotection on the gastrointestinal mucosa that are independent of the acid secretion. This has recently been documented in man. A clinical study was performed to test whether this mucosal reinforcing property also could be used to accelerate duodenal ulcer healing. Twenty-eight patients with endoscopically confirmed duodenal ulcers were randomized to treatment with PGE2 0.5 mg three times daily and 1 mg at night or to placebo under double-blind conditions during a four week period. To reduce antacid consumption a fluid placebo antacid was given regularly. An active antacid could be used for pain relief. Healing rate was assessed with repeated endoscopies after 2 and 4 weeks. The treatment groups were comparable with respect to age, duration of ulcer history and present ulcer symptoms, smoking habits, family history, gastric acid secretory rate and number of patients with blood group 0. There was a slight difference in sex distribution. 2 mg PGE2 did not reduce pentagastrin-stimulated acid secretion in five of the patients. After the treatment significantly more in the PGE2-group ( , 86%) had healed than in the placebo-group . There was no difference in pain relief between PGE2 and placebo-treated. The antacid consumption was very low in both PGE2 and placebo-treated. No significant side effects or changes in laboratory test-results were recorded. It is suggested that the cytoprotective effect of PGE2 can be used to accelerate healing of duodenal ulcer.  相似文献   

18.
The effect of a new analogue of PGE1 (CL115, 574) on gastric acid secretion, mucus secretion and protection against stress and indomethacin- induced ulcers were studied in the rat. CL115, 574 was more potent than PGE1 and cimetidine in inhibiting acid secretion. CL115, 574 protected against the development of stress and indomethacin-induced ulcers prevented the indomethacin-induced decrease in hematocrit at an ED50 (3 μg/kg) far below the antisecretory ED50 (1 mg/kg). While the inhibiting acid secretion, CL115, 574 increased the volume of gastric secretion indicating a stimulation of nonparallel cell secretion by the rat stomach. In addition the compound stimulated the secretion of mucus into the gastric juice. On the basis of its potency as an inhibitor of acid secretion and these additional effects which are indicative of cytoprotective activity, CL115, 574 should be further studied as a possible anti-ulcer agent in man.  相似文献   

19.
Two prostaglandin analogs, 15(S)-15-methyl PGE2, methyl ester, and 16, 16-dimethyl PGE2 were administered to human volunteers for their possible effect in inhibiting gastric secretion. Both analogs, given orally, inhibited gastric secretion stimulated by pentagastrin, and the effect was dose dependent. The inhibition lasted for more than 4 hours, and no side-effects were noted at the doses used. When given intraduodenally, through a thin tube swallowed the night before, 15(S)-15-methyl PGE2, methyl ester was more active than 16, 16-dimethyl PGE2. In view of their oral and prolonged activity, these analogs may have clinical potential in the treatment of peptic ulcer.  相似文献   

20.
Gastric ulcerogenicity and depletion of endogenous prostaglandins (PGs) content induced by tiaprofenic acid, dicrofenac and indomethacin were examined using the same antiinflammatory effective doses. Male Wistar rats were given each of these drugs intragasrically 24, 18, and 3 hrs before sacrifice in the following doses (mg/kg): indomethacin (0.8, 4 and 20); tiaprofenic acid (1.2, 6 and 30); dicrofenac (0.8, 4 and 20). Endogenous prostacyclin (PGI2) and PGE2 in fundic mucosa were determined by radioimmunoassay. The three compounds produced fundic mucosal lesions in a dose-dependent manner. However, tiaprofenic acid and dicrofenac were both less potent than indomethacin in producing gastric mucosal lesions at similar antiinflammatory doses. Mucosal PGE2 content was abolished by the three compounds in the following doses (mg/kg): indomethacin (4 and 20); tiaprofenic acid (6 and 30); dicrofenac (20). Mucosal PGI2 was maintained around 50% of the control value in rats given tiaprofenic acid in a dose of 6 mg/kg or dicrofenac in a dose of 4 mg/kg, while indomethacin in a dose of 4 mg/kg markedly reduced mucosal PGI2 to 17% of the control value. In larger doses, tiaprofenic acid and dicrofenac were also significantly less potent in reducing mucosal PGI2 than idomethacin. These results suggest that the difference in ulcerogenicity between idomethacin and the other two compounds was closely related to their potency in decreasing PGI2 in the gastric (fundic) mucosa.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号