Effect of aging on gastric acid secretion,serum gastrin,and antral gastrin content in rats

The purpose of this study was to characterize the effects of aging on gastric acid secretion and on serum and antral concentrations of gastrin in rats. Young and old Fischer 344 rats were prepared with gastric fistulas. Twenty-four hours after surgery, graded doses of human synthetic gastrin-17 (SHG-17) (2, 5, 10, 20, and 40 g/kg) were given intravenously in random order. Gastric secretions were collected for gastric acid measurement before and at 15-min intervals after each dose of gastrin. In a separate study, blood was collected and the stomachs were removed for antral gastrin extraction from fed young and old rats. Serum and antral gastrin was measured by radioimmunoassay. The basal and gastrin-stimulated acid secretions were significantly decreased in aged rats compared to the young rats. The basal acid output was 0.4±0.2 eq/15 min in the aged rats and 1.5±0.5 eq/15 min in the young. The maximal acid output stimulated by gastrin was 11.1±1.8 eq/15 min in the aged rats and 24.2±2.8 eq/15 min in the young. Both serum and antral concentrations of gastrin were significantly decreased in aged rats. Serum gastrin concentration was 114.8±7.4 pg/ml in the aged rats and 192.0±14.4 pg/ml in the young. Antral gastrin concentration was 3.9±0.5 g/g tissue in the aged rats, which was significantly less than the concentration in the young (6.5±0.4 g/g tissue). Antral gastrin content did not change with aging. Gastric acid secretion in aged rats is significantly decreased compared to the young in both the basal condition and in response to fixed doses of exogenous gastrin. Diminished concentrations of circulating gastrin may well be responsible, at least in part, for the diminished acid secretion in the aged rats.Part of this work was presented at the special session on aging during the Digestive Disease Week held by the American Gastroenterology Association (AGA) in New York, May 14, 1985, and has been published in abstract form (Gastroenterology 88:1445, 1985).Supported by grants from the National Institutes of Health (RO1 DK 15241, PO1 DK 35608, RCDA CA 00854, CA 38651) and a grant from the American Cancer Society (PDT-220).     

Effect of acupuncture on gastric acid secretion in healthy male volunteers

Six randomized, placebo controlled studies were performed to investigate the effect of electroacupuncture on gastric acid output in 38 healthy males. Electroacupuncture decreased basal acid output when compared to placebo acupuncture [from 3.50±0.59 mmol/hr to 2.54±0.56 mmol/hr (P<0.05)] as well as sham feeding-stimulated acid output [from 18.52±2.25 mmol/hr to 5.38±2.11 mmol/hr (P<0.005)], but had no effect on the pentagastrin stimulated acid output. The inhibitory effect of acupuncture on sham feeding-stimulated acid output was not affected by local anesthesia of the acupoint, but was prevented by a prior intravenous naloxone injection. Acupuncture did not alter plasma gastrin levels (20.7±7.6 g/liter, vs control 21.2±7.2 g/liter) but naloxone increased it (26.1±14.5 g/liter) (P<0.05). We conclude that the antisecretory effects of electroacupuncture do not result from decreased gastrin release or decreased parietal cell sensitivity to gastrin, but are mediated through naloxone-sensitive opioid neural pathways and vagal efferent pathways.Dr. Tougas was supported by a Fellowship of the Medical Research Council of Canada.This work was presented in part at the Annual Meeting of The American Gastroenterological Association, New Orleans, May 1988; Washington, May 1989; and San Antonio, May 1990.     

电针足三里穴对胃酸分泌的影响及与促胃液素、表皮生长因子的关系

目的探讨电针足阳明胃经原穴足三里穴对胃酸分泌的调节作用及机制.方法采用完全随机方法分组.在清醒状态下电针大鼠足三里穴,并与空白对照组及非经非穴组相对比,在针剌不同时间点测胃酸分泌及取血,放免法检测胃液及血浆促胃液素(GAS)和表皮生长因子(EGF)浓度.结果电针足三里穴后空腹胃液量显著减少(P＜0.01)pH值上升(P＜0.05),酸度变化不大.足三里穴组胃液及血浆GAS浓度均降低,分别为239 ng/L±61 ng/L vs 294 ng/L±32ng/L(P＜0.05)和81 ng/L±22ng/L vs 102ng/L±30 ng/L(P＜0.01).胃液EGF浓度显著升高3.16μg/L±1.05 μg/L vs 1.65μg/L±0.35μg/L(P＜0.01).血浆EGF浓度显著降低0.25μg/L±0.01μg/L vs 0.54 μg/L±0.11μg/L(P＜0.01).其他组无显著变化.结论电针足三里穴明显抑制胃酸分泌并使胃液pH升高,与血浆、胃液GAS下降有关;电针足三里穴诱导上消化道EGF分泌增加,EGF参与抑制胃酸分泌,具有重要意义.     

Changes in gastric acid secretion assayed by endoscopic gastrin test before and after Helicobacter pylori eradication

BACKGROUND: It remains controversial whether or not Helicobacter pylori infection causes altered gastric acid secretion. A novel test for evaluating gastric acid secretion (endoscopic gastrin test; EGT) has recently been developed. AIM: To investigate by EGT the effects of H pylori eradication on the state of gastric acid secretion in patients with peptic ulcer. METHODS: Twenty six patients with duodenal ulcer and 33 with gastric ulcer, for all of whom H pylori infection had been documented, were studied by EGT, histological examination of gastric mucosa, and measurement of plasma gastrin levels before and one and seven months after H pylori eradication. RESULTS: In patients with duodenal ulcer, the mean EGT value before H pylori eradication was higher than that in H pylori negative controls, but it had decreased significantly seven months after the treatment. In contrast, the mean EGT value of patients with gastric ulcer before H pylori eradication was lower than that in H pylori negative controls, but it had increased one month after the treatment; this was followed by a slight decrease at seven months. In both groups, mean EGT values seven months after the treatment were not significantly different from the mean control value. CONCLUSIONS: The reduced acid secretion in gastric ulcer patients and gastric acid hypersecretion in duodenal ulcer patients were both normalised after the clearance of H pylori.     

The gastric secretion and serum gastrin level in chicken

AIM To report a new method designed to collect gastric juice from chicken, and determine the basal levelof gastric acid and serum gastrin, and the effect of pentagastrin on gastric acid output.METHODS White Leghorn chickens, weighing 1.3 kg- 1.7 kg, deprived of food 24 h prior to experiment,were anaesthetized with pentobarbital sodium (60μg/kg, im). A reverse double lumen perfusion cannulawas introduced into the distal portion of the proventriculus through the crop incision. The perfusate drainedout from the cannular outlet was collected to determine the gastric acid. Gastric acid volume was determinedby titration with 0.01N NaOH. Serum gastrin levels were measured by radioimmunoassay using gastrin assaykit.RESULTS Acid output in the basal state was 0.041±0.006 mmol/L/10min, or 0.246±0.031mmol/L/h. The serum gastrin concentration was 78.27±19.19 pg/mL (n = 22). Three groups wereinjected pentagastrin at three dose level, 20μg/kg, 60μg/kg, 120μg/kg, respectively. The maximumoutput in three groups was 275%, 181% and 167% of their control acid output. Isoproterenol at a dose of0.3 mg/kg produced obvious inhibition of pentagastrin-stimulated gastric secretion. The effect ofisoproterenol on gastric secretion was completely abolished by propranolol, a β-receptor antagonist, but wasnot done by practolol, another 31-receptor antagonist.CONCLUSION The basal gastric acid output of chicken was high. Pentagastrin remarkably stimulatedgastric acid secretion, which could be inhibited by isoproterenol.     

Intestinal fat digestion plays a significant role in fat-induced suppression of gastric acid secretion and gastrin release in the rat

We have investigated the role of intestinal fat digestion in fat-induced suppression of gastric acid secretion and gastrin release in the rat. Intraduodenal administration of oleic acid (10%, pH 6.5) and triglyceride (10%, pH 6.5) at a rate of 2 ml/hr resulted in significant suppression of gastric acid secretion and gastrin release stimulated by intragastric perfusion of peptone (0.5%). Diversion of pancreatic juice from the duodenum completely abolished triglyceride-induced inhibition of peptone-stimulated gastric acid secretion and plasma gastrin release, but oleic acid-suppressed gastric acid secretion and gastrin release were unaffected by pancreatic juice diversion. Intraduodenal administration of digested triglyceride, prepared by preincubation with lipase, caused significant suppression of the peptone-induced gastric acid secretion and rise in plasma gastrin levels, even though pancreatic juice was excluded. The results of this study indicate that digestive products of triglyceride by pancreatic juice, especially by lipase, are responsible for the intestinal fat-induced inhibition of gastric acid secretion and gastrin release and that intestinal fat digestion plays a significant role in the mechanism.Part of this work was presented at the Annual Meeting of the American Gastroenterological Association, May 19–22, 1991, New Orleans, and appeared in abstract form inGastroenterology 100:A160, 1991.     

Cholecystokinin is not a physiological regulator of gastric pepsin secretion in rats

The physiological relevance of cholecystokinin (CCK) in gastric pepsin secretion is unclear, although CCK has been reported to stimulate pepsin secretion in intact animals and in dispersed chief cell. To clarify the physiological role played by this peptide in pepsin secretion, we determined the effects of intravenous infusions of CCK on gastric pepsin release, and investigated the effect of endogenous CCK released by small amounts of trypsin inhibitor on pepsin secretion in conscious rats. The infusion of CCK-8 at 1 nmol/kg per h resulted in a plasma CCK concentration of 204 pM and a 2.5-fold increase in pepsin secretion compared to the baseline rate. The infusion of CCK-8 at 0.3 nmol/kg per h resulted in a plasma CCK concentration of 41.8 pM and also caused a significant increase in pepsin secretion compared to the baseline rate. However, the infusion of CCK-8 at 0.1 nmol/kg per h (plasma CCK level, 19.9 pM), which is still far beyond the physiological plasma levels of CCK, did not significantly affect pepsin secretion. In addition, the intraduodenal infusion of soybean trypsin inhibitor increased the plasma CCK concentration to 4.4 pM, a value comparable to that observed after feeding (3.3 pM), but again, this had no effect on gastric pepsin secretion. We conclude that CCK is not a physiological regulator of gastric pepsin secretion in rats.     

Effect of Helicobacter pylori on Parietal Cell Sensitivity to Pentagastrin in Duodenal Ulcer Subjects

Chittajallu RS, Howie CA, McColl KEL. Effect of Helicobacter pylori on parietal cell sensitivity to pentagastrin in duodenal ulcer subjects. Scand J Gastroenterol 1992;27:857-862.

We have investigated the possibility that hypergastrinaemia in chronic Helicobacter pylori infection is a compensatory response to reduced parietal cell sensitivity to gastrin. The acid response to 45-min infusions of pentagastrin at sequential doses (mg/kg/h) of 0, 0.031, 0.062, 0.124, and 0.6 was compared before and 1 month after eradication of H. pylori in eight duodenal ulcer patients. The median acid outputs (mmol/h) with the respective infusions were 5.0, 7.5, 26.5, 30.8, and 37.0 when H. pylori-positive and similar at 4.5, 7.1, 22.7, 28, and 31.5 when H. pylori-negative. The median estimated dose of pentagastrin required to produce 50% maximal response (D₅₀) was similar before (0.060 mg/kg/h) and after (0.057 mg/kg/h) eradication of H. pylori. The median estimated maximal response to pentagastrin (mmol/h) was also similar before (39.2) and after (32.3) treatment. The median basal gastrin concentration was 48 ng/1 (range, 22-77) before treatment and fell to 33 ng/1 (range, 8-37) after eradication of H. pylori (p = 0.03). These findings show that the parietal cell sensitivity to pentagastrin is unaffected by chronic H. pylori infection in duodenal ulcer subjects and that the hypergastrinaemia cannot be attributed to the bacterium inhibiting parietal cell function.     

Verapamil decreases ethanol-induced gastric acid secretion in rats

The present study examined the effect of verapamil, a calcium channel blocker, on gastric acid secretion and circulating gastrin levels in rats after ethanol challenge. Normal saline or verapamil were given intraperitoneally to different groups of rats at 1 min, 1 h or 2 h before the administration of ethanol. One hour later, gastrin and gastric acid concentrations were determined. Regression analysis revealed the relationship between gastric acid output and serum gastrin levels in the group receiving saline intraperitoneally and ethanol orogastrically and the group receiving saline both intraperitoneally and orogastrically is similar. The slope of the regression line of the ethanol-challenged group treated with verapamil, however, was significantly lower than the slopes of the other two groups (P less than 0.001). Furthermore, verapamil decreased gastrin levels and acid output significantly in the ethanol-challenged group (P less than 0.01). When given 10 min prior to ethanol challenge, verapamil had a greater acid suppression effect than when given 60 or 120 min before the challenge. Verapamil at 20 mg/kg was more effective in acid secretion than at 10 mg/kg bodyweight, when administered 60 min before ethanol challenge.     

促胃液素及其受体拮抗剂丙谷胺对人胃癌细胞系生长的影响

目的观察和分析五肽促胃液素ＰＧ及其受体拮抗剂丙谷胺ＰＧＭ对人胃癌细胞系ＭＧＣ生长的影响,为临床应用促胃液素受体拮抗剂协助治疗胃癌提供依据．方法选用５ｍｇ／Ｌ,１０ｍｇ／Ｌ,１５ｍｇ／Ｌ,２０ｍｇ／Ｌ４种浓度的ＰＧ和３０ｍｇ／Ｌ的ＰＧＭ分别作用于体外培养的浓度为２５×１０８／Ｌ的ＭＧＣ,分别培养２４,４８,７２ｈ,于酶标仪上选用波长５４０ｎｍ测定吸光值Ａ,并对数据进行比较分析．结果４种浓度的ＰＧ作用于ＭＧＣ,ＭＧＣ连续３ｄ的生长状态与对照组无明显差异,而ＭＧＣ在ＰＧＭ作用下,其连续３ｄ的平均Ａ值分别为００２９,００４６和００８４,而未被ＰＧＭ作用的ＭＧＣ的平均Ａ值分别是０１０１,０１１５和０１８２,ＭＧＣ在ＰＧＭ作用下生长明显低于对照组（Ｐ＜００５）．结论外源性的ＰＧ对ＭＧＣ无营养促进作用,而ＰＧＭ能抑制ＭＧＣ的生长     

Effects of Helicobacter pylori infection on gastric acid secretion and serum gastrin levels in Mongolian gerbils

BACKGROUND AND AIMS: Body gastritis caused by Helicobacter pylori infection appears to inhibit gastric acid secretion. The aim of this study was to determine the effects of H pylori infection on gastric acid secretion and clarify its mechanisms with reference to interleukin 1beta (IL-1beta). METHODS: (1) Mongolian gerbils were inoculated orally with H pylori. Before, six, and 12 weeks after inoculation, serum gastrin levels, gastric acid output, and IL-1beta mRNA levels in the gastric mucosa were determined. Pathological changes were also determined according to the updated Sydney system. (2) Effects of recombinant human IL-1 receptor antagonist (rhIL-1ra) on gastric acid output and serum gastrin levels were also determined. RESULTS: (1) Scores for activity and inflammation of gastritis and serum gastrin levels were significantly increased, and gastric acid output was significantly decreased six and 12 weeks after inoculation with H pylori. IL-1beta mRNA levels in the gastric mucosa were also elevated six and 12 weeks after inoculation with H pylori. (2) Acid output and serum gastrin levels in the infected groups returned to control levels after rhIL-1ra injection. CONCLUSIONS: Gastric acid secretion is decreased and serum gastrin levels are increased in Mongolian gerbils infected with H pylori. This change in gastric acid secretion appears to be mediated by IL-1beta induced by H pylori infection.     

Effect of nicotine in migration and proliferation of rabbit gastric mucosal cells in a culture cell model

Abstract The aim of this study was to assess the effects of nicotine on the gastric epithelial restoration using primary cultured rabbit gastric mucosal cell model.
Confluent monolayer mucosal cell sheets consisting of mainly mucous cells were wounded using a rotating silicon tip. The process of restoration was monitored, and the size of wound was measured and analysed quantitatively.
Artificial wounds recovered in 36 h in controls. The nicotine treatment (10⁻⁵, 10⁻⁴ and 10⁻³ mol/L) did not cause any effects on the process of wound repair. Bromodeoxyuridine (BrdU) positive cells appeared around the wound 24-36 h after injury and then disappeared after the complete repair in controls and also in nicotine-treated groups. However, in the morphological observation, numerous vacuoles were detected in parietal cells of nicotine-treated groups. This effect of nicotine was reversible by removing nicotine from the medium. Present data suggest that nicotine has no direct effects on the mucosal restoration but might have an effect on the structure and function of parietal cells.     

Gastric secretion during aging in pyloric-ligated rats and effects of pentagastrin

Changes in basal- and pentagastrin-stimulated gastric acid, pepsin secretion as well as gastric mucosal histidine decarboxylase activity were examined in 4- to 21-month-old pyloric ligated Fischer-344 rats. In addition, serum gastrin levels, gastric mucosal DNA, and RNA content were determined in these rats. The results revealed that whereas acid secretion decreased progressively with age, pepsin output increased between 4 and 14 months of age and then decreased sharply. Serum gastrin levels decreased progressively with age, and 3 h of pyloric obstruction produced no apparent change in serum gastrin levels in any of the age groups. Gastric mucosal weight, DNA, and RNA content in 4-month-old rats were not significantly different from those of 14-month-old animals. However, in 21-month-old rats, each of these values were found to be significantly lower than in their 4- or 14-month-old counterparts. A single injection of pentagastrin (250 μg/kg) significantly stimulated acid and pepsin secretion (45–52%) in 4-month-old rats, but not in 14- and 21-month-old animals, when compared with the corresponding saline-injected controls. Gastric mucosal histidine decarboxylase activity increased steadily between 4 and 21 months of age. Pentagastrin caused a significant 78% stimulation in histidine decarboxylase activity in 4-month-old rats, but had no effect on the enzyme activity in 14-month-old animals, when compared with the corresponding saline-injected controls. However, in 21-month-old rats, pentagastrin inhibited histidine decarboxylase activity by 55% when compared with the saline-injected controls. It is concluded that a) aging decreases capacity of the gastric mucosa to secrete acid and pepsin, b) in aged rats, decreased acid and pepsin output could in part be attributed to mucosal atrophy; c) responsiveness of the gastric mucosa to pentagastrin decreases with age; and d) in aged animals, gastric acid secretion is not regulated by histamine.     

Regulation of gastric function by endogenous gastrin releasing peptide in humans: studies with a specific gastrin releasing peptide receptor antagonist

BACKGROUND AND AIMS: The main goal of our study was to characterise the activity of BIM26226 as a peripheral gastrin releasing peptide (GRP) receptor antagonist in healthy human subjects and to determine if endogenous GRP is a physiological regulator of gastric acid secretion and gastrin release. METHODS: Our study consisted of three parts. In part I, subjects received saline or BIM26226 followed by graded doses of intravenous human GRP in a four period crossover design. In part II, subjects received BIM26226 or saline during oral meal ingestion or modified sham feeding. In part III, subjects received an acidified meal in the presence and absence of BIM26226 in a two period crossover design. In addition, gastrin and somatostatin mRNA were measured in biopsy specimens during saline and BIM26226 infusion. RESULTS: BIM26226 dose dependently inhibited GRP induced acid output. Acid secretion after oral liquid meal intake and sham feeding was significantly inhibited by BIM26226 (p<0.01) whereas plasma gastrin release remained unchanged. Gastrin and somatostatin mRNAs were not significantly different after saline or BIM26226. CONCLUSIONS: BIM26226 is a potent GRP antagonist in humans. Endogenous GRP may be a physiological regulator of gastric acid secretion. Gastrin release does not seem to be under the control of GRP.     

Gastric acid secretion and gastrin release in the baboon

Significant species differences have been demonstrated in gastric physiology, a factor that limits extrapolation of animal data to man. Primate physiology is thought to be similar to that of man; however, gastric function has not been adequately documented in the primate. In the present study six baboons (body weight 25.5±1.8 kg) were trained to sit in a chair and gastric acid secretion and gastrin release was studied in conscious animals. Mean basal acid secretion was 1.3±0.1 mmol (H⁺)/hr. Maximum output after pentagastrin (12 g/kg/hr) was 9.5±0.9 mmol (H⁺)/hr and 11.0±0.4 mmol (H⁺)/hr after histamine (40 g/kg/hr). A statistically significant (by cosinor analysis) circadian rhythm was demonstrated for intragastric pH over 24 hr in fasted baboons (P<0.001). Mean basal serum gastrin level was 37.7±8.3 pg/ml. The integrated gastrin response after administration of a protein rich meal was 2.52±0.07 ng×min/ml and this increased to 5.17±0.18 ng×min/ml (P<0.05) following simultaneous administration of a meal with atropine (0.2 mg/kg) (P<0.05). Our results suggest that there is significant basal and stimulated acid secretion in the baboon; the amount of acid secreted is similar to that reported in man. Gastric pH demonstrated a circadian rhythm. Postprandial gastrin release was significantly enhanced by cotreatment with atropine. As the present findings are similar to those previously reported in man, the baboon may be a useful model for further studies in gastric physiology and experimental peptic ulceration.     

Pathophysiology of gastric acid secretion in patients with chronic renal failure: influence of Helicobacter pylori infection

OBJECTIVES: The incidence of gastroduodenal diseases is high in patients with chronic renal failure (CRF). However, gastric acidity in CRF has been reported to range in level from low to high. Moreover, it remains unknown whether Helicobacter pylori infection influences gastric acidity in such patients. Thus, we aimed to clarify the pathophysiological perturbation in gastric acidity and to determine the influence of H. pylori infection in CRF. DESIGN: Case-control study. SETTING: A university hospital. SUBJECTS: Twenty-seven patients with CRF and 24 control patients, presenting with either gastrointestinal symptoms, positive faecal occult blood, or anaemia (haemoglobin <10 g dL(-1)). MEASURES: The patients underwent gastroduodenal endoscopy with simultaneous determination of H. pylori infection. Gastric ammonium concentration, serum pepsinogen I and II, and basal gastrin level were measured. Thereafter, gastric acid secretion was monitored by 24-h intragastric acidity measurement with calculation of pH-3 holding time (%) (hours showing pH>3/24 h). RESULTS: In the CRF group, pH-3 holding time of H. pylori (+) subgroup was significantly greater than that of H. pylori (-) subgroup (71.2 +/- 32.4% vs. 32.8 +/- 30.0%, mean +/- SD; P=0.03). Pepsinogen I/II ratio was inversely correlated with pH-3 holding time in the control and CRF groups. Gastric ammonium concentration in CRF/H. pylori (+) subgroup (14.1 +/- 9.2 mmol L(-1)) was significantly higher than in CRF/H. pylori (-) (2.5 +/- 2.7 mmol L(-1); P=0.002) and control/H. pylori (+) subgroups (6.1 +/- 4.2 mmol L(-1); P=0.01). Serum gastrin level was significantly higher in the CRF group than in the control group (297 +/-343 pg mL(-1) vs. 116 +/- 69 pg mL(-1); P=0.02) as a whole. However, there was no significant correlation between serum creatinine and gastrin levels in the CRF group. Gastrin level in CRF/H. pylori (+) subgroup was significantly higher than in CRF/H. pylori (-), control/H. pylori (+), and control/H. pylori (-) subgroups (423 +/-398 pg mL(-1) vs. 113 +/- 79, 124 +/- 78, and 96 +/-43 pg mL(-1), respectively; P=0.01-0.03). Significant positive correlations amongst pH-3 holding time, ammonium and gastrin concentrations were found in the CRF group, but not in the control group. CONCLUSIONS: CRF without H. pylori infection primarily shows a tendency for high gastric acidity, but without hypergastrinaemia. Persistent H. pylori infection in CRF leads to decreased acidity and, consequently, to fasting hypergastrinaemia via a feedback mechanism. The hypoacidity in CRF with H. pylori infection appears to result from neutralization of acid by ammonia as well as from gastric atrophy. Thus, H. pylori infection status critically determines perturbation in gastric acidity and fasting gastrin level in CRF.     

Topical nicotine protects rat gastric mucosa against ASA-induced damage a role for mucosal fluid secretion in cytoprotection

Acute intragastric nicotine administration has previously been shown to protect against ethanol-induced gastric mucosal damage. The aim of this study was to examine the effects of acute nicotine exposure on ASA-induced gastric mucosal damage and to determine if nicotine's protective effect is secondary to an increase in mucosal blood flow or in mucosal fluid secretion, as reflected by changes in the juxtamucosal pH gradient and volume of intragastric fluid. Mucosal blood flow, using a laser Doppler flowmeter, juxtamucosal pH gradient (depth, magnitude, and surface pH), using antimony microelectrodes, and changes in volume of luminal bathing solutions were measured in ratex vivo gastric chamber preparations prior to and after a 10-min exposure to topical nicotine (1 mg in 8 ml of 0.2 M mannitol in 50 mM HCl), or to mannitol-HCl solution (vehicle). This was followed by application of acidified ASA (80 mM in 160 mM HCl) to the chambered mucosae for 10 min. Lesion area, expressed as the percentage of total glandular mucosa which was damaged, was significantly (P<0.05) reduced by nicotine pretreatment. Blood flow decreased with nicotine exposure by 18.4%, compared to 13.6% in the control group (NS). Both gradient depth and gastric fluid volume increased significantly in the nicotine group (P<0.05) compared to controls. Yohimbine pretreatment prevented both the increase in juxtamucosal pH gradient depth and the protective effect of nicotine. These results suggest that acute intragastric nicotine exposure protects against ASA-induced gastric damage in rats. This protection is not due to increased mucosal blood flow, but may be due to increased mucosal secretion, as reflected by an increase in the pH gradient depth, and an increase in the intragastric volume.This research was supported by a grant from the Natural Sciences and Engineering Research Council of Canada     

The effects of smoking and nicotine on the parietal cell mass of human beings and rats

Abstract On 94 patients with duodenal ulcer and 44 controls, parietal cell mass (PCM), as derived from pentagastrin-stimulated peak acid output (PAO), was significantly greater in chronic cigarette smokers than in non-smokers. Smokers and non-smokers did not differ in their fasting and postprandial serum gastrin concentrations, and in the frequency of familial ulcer, although basal acid output (BAO) and BAO/PAO were significantly higher in smokers, suggesting the presence of hypervagotonia. Chronic hypodermic administration of depot nicotine in rats resulted in significant dose-dependent increase in PAO and PCM as determined histologically, supporting the results of the human studies. Acute administration of nicotine, however, did not cause any increase in acid output, indicating that it had no effect on parietal cell function. Chronic nicotine administration also led to significant increase in antral G cell mass as determined by immunohistochemical labeling, and in peptone-stimulated serum gastrin. The effects on PCM and G cells were abolished by the simultaneous administration of atropine. Nicotine induced gastric electrical and motor activities in rats similar to those induced by carbachol, and the effects of both agents could be blocked by atropine. Nicotine had no effect on gastric mucosal blood flow in rats as estimated by neutral red clearance. We conclude that cigarette smoking in man and chronic nicotine administration in rats cause parietal cell hyperplasia, plus, in rats, G cell hyperplasia, possibly through a cholinergic mechanism.     

Does sulfation of gastrin influence gastric acid secretion in man?

To assess the physiologic significance of tyrosine o-sulfation of gastrin in humans, the gastric acid stimulatory potencies of sulfated and non-sulfated human gastrin-17 were compared in six normal young subjects. Sulfated and non-sulfated forms of synthetic human gastrin-17 were infused intravenously in doses from 12.7 to 478 pmol/kg/h. Similar acid secretory responses were observed. The calculated maximal acid response for sulfated gastrin-17 was 35.7 +/- 4.3 mmol/h, and that for non-sulfated gastrin-17 was 39.8 +/- 7.5 mmol/h (mean +/- SEM, NS). The 50% effective dose of sulfated gastrin-17 was 22.2 +/- 6.7 pmol/kg/h, whereas it was 29.3 +/- 5.8 pmol/kg/h for non-sulfated gastrin-17 (NS). Finally, the 50% effective concentration of gastrin in serum was 34.7 +/- 5.0 pmol sulfated gastrin-17/l and 42.5 +/- 11.8 pmol non-sulfated gastrin-17/l (NS). The results show that tyrosine o-sulfation is without significant influence on the gastric acid secretory potency of gastrin in man. Moreover, the results also suggest that sulfated and non-sulfated gastrin-17 in man have similar rates of metabolism.     

Effect of misoprostol on histamine-stimulated acid secretion and cyclic AMP formation in isolated canine parietal cells

Isolated canine parietal cells were used to study the ability of misoprostol to inhibit acid secretion in the presence of a number of acid secretagogues. Misoprostol inhibited histamine-stimulated acid secretion in a dose-dependent and noncompetitive manner. A concentration of 2–3×10^–9 M misoprostol inhibited maximal histamine-stimulated acid secretion by one half. Misoprostol had little to no effect on acid secretion stimulated by carbachol and dibutyryl cAMP, had no effect on the acid secretion directly stimulated by pentagastrin, and only modestly inhibited acid secretion stimulated by forskolin. Misoprostol noncompetitively inhibited cAMP formation in response to histamine, with an IC₅₀ value similar to that for the inhibition of histamine-stimulated acid secretion. These results indicate that: (1) misoprostol specifically inhibits histamine-stimulated acid secretion in parietal cells, and (2) the antisecretory action of misoprostol is closely related to the reduction of histamine-stimulated cAMP formation with the site of major action most likely in the coupling process between histamine H₂ receptor sites and histamine-sensitive adenylate cyclase.