Effect of atropine and somatostatin on bombesin-stimulated plasma gastrin,cholecystokinin and pancreatic polypeptide in man

Infusion of the neuropeptide bombesin stimulates the secretion of several gastrointestinal hormones by an unknown mechanism. We have investigated the effects of atropine (15 ng/kg as bolus followed by 2.5 ng/kg · 30 min) and somatostatin (125 μg as i.v. bolus followed by 62.5 μg/30 min) on the stimulation of 3 hormones (gastrin, cholecystokinin and pancreatic polypeptide) by 60 pmol/kg · 20 min bombesin in 6 healthy volunteers. Plasma samples for measurement of hormones by sensitive and specific radioimmunoassays were obtained at − 5, 0, 2.5, 5, 7.5, 10, 15, 20, 25 and 30 min. Bombesin induced significant increases in plasma gastrin (12 ± 2 to 34 ± 3 pM; P < 0.0005), cholecystokinin (1.2 ± 0.2 to 8.9 ± 0.7 pM; P < 0.0001) and pancreatic polypeptide (22 ± 4 to 72 ± 19 pM; P < 0.05). There were great differences between the effects of atropine and somatostatin on the hormonal responses to bombesin. Atropine slightly increased the response of gastrin by 19% and that of cholecystokinin by 15%, but strongly inhibited the bombesin-stimulated pancreatic polypeptide secretion by 97%. On the other hand, somatostatin inhibited the bombesin-induced secretion of gastrin by 48%, cholecystokinin by 82% and pancreatic polypeptide by 107%. These results point to considerable qualitative and quantitative differences in the stimulatory mechanisms of bombesin on the hormones studied.     

Differential stimulation of pancreatic-polypeptide and gastrin secretion by bombesin in man

Bombesin, besides many other actions on the mammalian gastroentero-pancreatic tract, strongly stimulates the release of pancreatic-polypeptide (PP) in dogs. In 8 healthy human volunteers (5 males, 3 females), the PP response during bombesin infusion was low (25.7 ± 6.3 peak vs. 5.0 ± 2.0 basal pmol/1) compared to the effect of a protein meal (144.1 ± 13.4 pmol/1) or to the gastrin response to the same dose of the amphibian polypeptide (140.0 ± 23.6 pmol/1 eq SHG 17 I). The response pattern of PP and gastrin was different as PP concentrations peaked 10 min after cessation of bombesin infusion (32.0 ± 4.9 pmol/1) when gastrin concentrations already were down to one third of the maximal response. Atropine inhibited the PP response to bombesin but did not abolish it completely. It is concluded that in man, the total effect of bombesin on PP secretion is minor compared both to the effect of the peptide on gastrin secretion in man and to the effect of bombesin in dogs. It is suggested that bombesin might have a dual, inhibitory-stimulatory, effect on PP secretion in man.     

The importance of cholinergic tone in the release of pancreatic polypeptide by gut hormones in man.

The pancreatic polypeptide response to both caerulein and Boots' secretin was greatly obtuned by prior administration of atropine. In addition basal plasma PP concentration fell by 54 ± 7% (mean ± SEM p < 0.001) 30 minutes after atropinisation. Some degree of cholinergic tone thus appears essential both for maintaining basal PP levels and for the response to gut hormones.     

Pancreatic polypeptide response to ethanol in humans and dogs

We studied the effect of a drink of various concentrations of pure ethanol and several commonly ingested alcoholic beverages on plasma levels of immunoreactive pancreatic polypeptide in six healthy human volunteers and compared the results to a protein-rich meal. A drink of distilled water (250 ml) and of pure ethanol (250 ml or 125 ml in the case of 40% v/v ethanol) in concentrations (4, 10, 20, and 40%, v/v) normally present in beer, wine, liquor and whisky did not stimulate plasma pancreatic polypeptide levels above basal. Neither beer, red and white wine (250 ml each) nor whisky (125 ml) caused an increase in basal plasma pancreatic polypeptide levels. The 90-min integrated plasma pancreatic polypeptide response to the protein-rich meal was significantly reduced by an additional drink of 250 ml of white wine ($\text{5987 ± 1315}$ versus $\text{4126 ± 809}\text{pmol · min}{}^{\mathrm{?1}}\text{· 1}{}^{\mathrm{?1}}$). An intravenous infusion of ethanol (300 mg · kg^?1 over 30 min) did not increase plasma pancreatic polypeptide levels above basal.In six dogs with gastric and duodenal fistulas the infusion of pure ethanol into a peripheral vein, into the stomach or into the duodenum did not alter plasma pancreatic polypeptide levels. When ethanol (200 ml of either 1.8, 10 or 40%, v/v) was given as an intragastric bolus injection, only 40% ethanol caused an increase in the mean 90-min integrated plasma pancreatic polypeptide response which was only one-twelfth of the pancreatic polypeptide response to an oral mixed meat meal (35 g · kg^?1). We conclude that in man neither an intravenous infusion nor a drink of ethanol in concentrations normally present in beer, wine and whisky, release pancreatic polypeptide. Also, beer, red and white wine and whisky have no effect on plasma pancreatic polypeptide concentrations. In dogs, a large amount of intragastric ethanol was needed to produce a very small rise in plasma pancreatic polypeptide levels. These results do not favour the hypothesis that, in man and dog, pancreatic polypeptide is the hormonal mediator of the ethanol induced inhibition of exocrine pancreatic secretion.     

The effect of atropine on bombesin and gastrin releasing peptide stimulated gastrin, pancreatic polypeptide and neurotensin release in man

The effects of 1-h infusions of bombesin and gastrin releasing peptide (GRP) at 50 pmol/kg per h and neurotensin at 100 pmol/kg per h on gastrin, pancreatic polypeptide (PP) and neurotensin release in man were determined following either saline or atropine infusion (20 micrograms/kg). Bombesin produced a rise in plasma neurotensin from 32 +/- 6 to 61 +/- 19 pmol/l and of PP from 26 +/- 8 to 36 +/- 7 pmol/l. There was a further rise of plasma PP to 50 +/- 13 pmol/l after cessation of the infusion. GRP had no significant effect on plasma neurotensin, but compared to bombesin, produced a significantly greater rise in plasma PP from 34 +/- 6 to 66 +/- 19 pmol/l during infusion. There was no post-infusional increase. At this dose, GRP was as effective as bombesin in releasing gastrin, although unlike bombesin its effect was enhanced by atropine. Neurotensin produced a rise in plasma PP from 17 +/- 4 to 38 +/- 8 pmol/l. Atropine blocked the release of PP during GRP and neurotensin infusion. Atropine had no effect on neurotensin or PP release during bombesin infusion, but did block the rise in plasma PP following bombesin infusion. We conclude that, in contrast to meal-stimulated neurotensin release, bombesin-stimulated neurotensin release is cholinergic independent. Despite structural homology, bombesin and GRP at the dose used are dissimilar in man in their actions and sensitivity to cholinergic blockade.     

Atropine depresses release of neurotensin and its effect on the exocrine pancreas

In this study the effect of 10 and 20 μg · kg^?1 · h^?1 atropine sulfate on release and pancreatic effects of neurotensin was studied in 4 dogs. Neurotensin plasma levels rose significantly when a liquid fat preparation was infused intraduodenally. This rise was almost completely abolished by simultaneous infusion of atropine. Atropine further suppressed basal and fat-stimulated output of pancreatic volume, protein, and bicarbonate; it also reduced pancreatic secretion stimulated by an intravenous infusion of low doses (2.5 to 20 pmol · kg^?1 · min^?1) neurotensin. The effect of higher doses (80 and 240 pmol · kg^?1 · min^?1) of neurotensin was less affected.As neurotensin plasma levels in contrast to normal oral feeding did not rise after sham feeding, our findings suggest that release and action of neurotensin may at least in part be dependent on a cholinergic, non-cephalic mechanism.     

Effect of neurotensin on pancreatic function in man

The effect of neurotensin on submaximally-stimulated hepatobiliary and pancreatic secretion was studied in 6 healthy subjects. An intravenous infusion of neurotensin 1.4 ± 0.3 pmol/kg/min, designed to reproduce plasma neurotensin immunoreactivity levels within the physiological range, produced a significant increase in pancreatic bicarbonate output. Plasma concentrations of pancreatic polypeptide rose by 83 ± 16 pmol/l and were associated with a small reduction in trypsin, but no significant change in bilirubin outputs.     

The effect of atropine and vagal stimulation on the release of neurotensin-like immunoreactivity in man

This study investigated the food stimulated release of neurotensin-like immunoreactivity (NTLI) in man with and without the administration of atropine, and the influence of vagal stimulation by modified sham feeding and insulin hypoglycaemia. NTLI was measured, after ethanol extraction, by specific C- and N-terminally directed antisera. With both a liquid fat meal and a mixed meal an early peak of NTLI occurred. The mixed meal also produced a second sustained rise in plasma NTLI. An intramuscular injection of 0.6 mg atropine sulphate abolished the early peak, but had no effect on the late peak. Modified sham feeding and insulin hypoglycaemia did not release NTLI. We conclude that it is possible that a cholinergic non-vagal mechanism is responsible for the early phase of food stimulated release of NTLI in man, and that the second sustained rise may be cholinergically independent.     

The influence of cadmium (CdCl2) on the canine plasma levels of gastrin,cholecystokinin (CCK), and pancreatic polypeptide (PP)

The influence of cadmium on basal and stimulated plasma levels of gastrin, cholecystokinin (CCK), and pancreatic polypeptide (PP) was investigated in conscious dogs using three doses of cadmium (0.15, 0.5, and 0.75 mg Cd/kg-h). Levels of gastrointestinal (GI) hormones were stimulated with bombesin (BBS), a peptide known to stimulate GI hormone release. Plasma cadmium was measured employing atomic absorption spectrophotometry and GI hormone levels were measured with specific radioimmunoassays (RIA). Basal plasma levels of hormones (pg/mL) in the dogs were in the range (mean ± SE): 38±5 to 44±6 for gastrin, 80±25 to 107±17, for CCK and 120±5 to 142±5 for PP; these levels did not change with cadmium. Significant increases above basal levels in all three hormones were found with infusions of BBS and with BBS plus cadmium. Gastrin levels remained steady during Cd and saline after BBS; however, CCK and PP levels dropped to values that were 68 and 73% less than their stimulated peak levels. With reinfusion of BBS, gastrin, CCK, and PP were significantly elevated above basal; however, the peak values for CCK and PP, but not gastrin, were less than those found during the first BBS infusion. The data suggest that in response to bombesin, cadmium has little or no effect on the release of gastrin, but that is exerts a latent effect on the release of both CCK and PP.     

Effect of truncal vagotomy on pancreatic polypeptide response after intravenous glucose administration

Intravenous glucose infusion was performed in six dogs with and without truncal vagotomy, and plasma pancreatic polypeptide (PP) responses were compared before and after truncal vagotomy. Following truncal vagotomy, basal PP levels decreased significantly from 286 ± 64 pg/ml (mean ± S.E.) to 94 ± 14 pg/ml (P < 0.05). Basal plasma insulin and blood glucose levels also tended to be lower, but not significantly. During the influsion of glucose, blood glucose concentrations rose rapidly in both groups and after 15 min reached peak values which were not significantly different from each other. In the vagotomized group the plasma insulin response to intravenous glucose infusion was significantly lower than in the control group. Following intravenous glucose loading, plasma PP concentrations decreased rapidly in both groups, but the PP level in the vagotomized group was suppressed only to 77 ± 4% of the basal level whereas in the control group it decreased to 45 ± 8%, significantly lower than in the vagotomized group (P < 0.01).These results suggest that basal PP is regulated by vagal tonus and that vagus controls, at least in part, suppression by intravenous glucose administration.     

Effect of bombesin-stimulated gastrin on gastric acid secretion in man

The effect of bombesin on gastrin release and gastric acid secretion was investigated in 10 healthy volunteers. Bombesin (0.6 μg · Kg^?1 · hr^?1) produced a significantly higher $\text{(}\text{p}\text{<}\text{0.001)}$ increase in plasma gastrin levels (86.7 11.1 pmo/1 than after a protein meal (39.6 ± 5.6 pmol1/1). The gastric acid secretory response to bombesin (12.1 ± 2.9 mEq · hr^?1) was however significantly lower $\text{(}\text{p}\text{<}\text{0.005)}$ than the maximal response produced by pentagostrin (20.9 ± 3.5 mEq · hr^?1) at the dose of 6 μg · Kg^?1. Atropine did not modify gastrin release induced by bombesin but significantly reduced gastric acid secretion $\text{(}\text{p}\text{<}\text{0.01)}$. From the data presented it may be hypothesized that less biologically active forms of gastrin and/or other peptides inhibiting the gastrin effect upon gastric acid secretion may be released by bombesin.     

Large and small forms of cholecystokinin in human plasma: measurement using high pressure liquid chromatography and radioimmunoassay

Defining the role of cholecystokinin (CCK) in gut physiology and disease has proved difficult because of problems with development of radioimmunoassays and because CCK exists in several different molecular forms which have different biological actions. In order to measure small (8 amino acid residues, CCK 8) and large (33 and 39 residues) forms of CCK in plasma we have developed high pressure liquid chromatographic (HPLC) fractionation of plasma prior to radioimmunoassay. Fasting plasma CCK 8 and CCK $\text{33}\text{39}$ levels were usually undetectable (< 3 and < 6 pmol/1, respectively). After a liquid fat meal both CCK 8 and CCK $\text{33}\text{39}$ levels were significantly elevated at 5 min (11.3±3.3 and 11.6±2.6 pmol/1, respectively). Peak CCK 8 levels occurred at 30 min (15.0±4.4 pmol/1) while peak CCK $\text{33}\text{39}$ levels occurred at 120 min (16.7±4.9 pmol/1. Total CCK levels showed a biphasic response to the meal. These CCK 8 and CCK $\text{33}\text{39}$ responses to oral fat are consistent with a role for these hormones in the regulation of gallbladder emptying and pancreatic secretion.     

Effect of a test meal,duodenal acidification,and tetragastrin on the plasma concentration of β-endorphin-like immunoreactivity in man

The effects of various test materials on plasma β-endorphin-like immunoreactivity (β-EpLI) were investigated in man using a specific radioimmunoassay developed by the authors. Plasma β-EpLI was determined after extraction by the acid/acetone method (recovery 73±5%). The intraassay and interassay coefficients of variation were 5.0% and 7.6%, respectively. The plasma concentrations of human β-EpLI in normal subjects were 11.6±4.0 pmol/l for men (n=23) and 10.7±4.8 pmol/l for women (n=27). Ingestion of a test meal (150 g of Campbell's condensed meat soup) resulted in a biphasic rise in plasma β-EpLI from the basal level of 4.4±1.0 pmol/l to 29.2±1.9 pmol/l after 5 min and 24.8±6.7 pmol/l after 90 min. Intraduodenal infusion of 115 ml of 0.1 M HCl over 10 min increased the plasma β-EpLI level from 8.7±0.5 pmol/l to 15.5±0.4 pmol/l at 10 min after the start of infusion, but the level rapidly returned to the initial value after the end of the infusion. Intramuscular injection of 4 μg/kg body weight of tetragastrin markedly stimulated gastric acid output and β-EpLI release, but pretreatment with 10 mg of histamine H₂ receptor antagonist inhibited the gastric acid output and plasma β-EpLI release induced by tetragastrin.These results indicate that β-EpLI release is stimulated by ingestion of meat soup, duodenal acidification and tetragastrin administration. It is suggested that gastric acid participates, at least in part, in postprandial release of β-EpLI, probably from the gastrointestinal tract.     

Effects of D-Chiroinositol Added to a Meal on Plasma Glucose and Insulin in Hyperinsulinemic Rhesus Monkeys

We have previously demonstrated that D-chiroinositol, administered intravenously to insulin-resistant monkeys, increases the rate of disappearance of plasma glucose and insulin. The purpose of the present study was to determine whether orally administered D-chiroinositol might also similarly improve the postprandial plasma glucose profile of hyperinsulinemic insulin-resistant monkeys. A complete liquid diet meal (15 ml/kg body weight) was ingested by each of six monkeys on two occasions separated by 10 days, with conditions identical except D-chiroinositol (500 mg/kg body weight) was added to the second meal. At 110 minutes following each meal, the monkeys were anesthetized and blood samples obtained at 120, 150, 180, 210, 240, 270 and 300 minutes. Plasma glucose and insulin concentrations were determined. The mean plasma glucose concentration (120 ? 300 minutes) was significantly lower after the meal containing D-chiroinositol compared to the control meal (7.1 ± 1.2 vs. 7.8 ± 1.2 mM) (p<0.05). Plasma insulin concentrations tended to be lower after the meal containing D-chiroinositol compared to the control meal (3930 ± 1068 vs. 4518 ± 1200 pM) (p<0.15, ns). We conclude that in hyperinsulinemic monkeys, D-chiroinositol added to a meal lowers postprandial plasma glucose without an increase in plasma insulin, and therefore may be a useful agent for reducing meal-induced hyperglycemia without inducing hyperinsulinemia.     

Meal-induced increase in plasma gastrin immunoreactivity in the rhesus monkey (Macaca mulatta)

The hormonal response to food intake in rodents, dogs, and humans involves gastrin and cholecystokinin, structurally related peptides present in plasma, gut, and brain. In order to determine the time course of plasma gastrin response in a nonhuman primate, six overnight-fasted adult male rhesus monkeys were offered a meal of bananas (11g) and peanut butter (1 Tbsp) or a fresh water bottle in a crossover design. All animals completely consumed the meal within 10 min. Compared to non-fed control levels, plasma gastrin was significantly elevated (52 ± 11 pM vs. 32 ± 9 pM, means ± S. E. M.) from 10 to 45 min post-ingestion, but returned to near basal fasted level by 120 min. Levels of gastrin in tissue samples (n = 2) were highest in the antrum of the stomach, with decreasing amounts measured in the upper and lower duodenum, respectively. The results demonstrate that the plasma concentration and response to a meal of rhesus monkey gastrin are similar to those of other mammalian species. However, the high concentrations of gastrin found in duodenum are thus far unique to Macaca mulatta and humans.     

Effect of nicotine on basal and bombesin stimulated canine plasma levels of gastrin, cholecystokinin and pancreatic polypeptide

The influence of nicotine on the basal and bombesin (BBS) stimulated plasma levels of gastrin, cholecystokinin (CCK) and pancreatic polypeptide (PP) was investigated in conscious dogs. Plasma levels of nicotine and gastrointestinal (GI) hormones were measured by employing gas liquid chromatography and specific radioimmunoassay (RIA). The basal levels of gastrin, CCK and PP were found to be in pg/ml (pmol/l) (mean +/- S.E.), 28 +/- 5 (13 +/- 3), 252 +/- 32 (66 +/- 8) and 347 +/- 136 (83 +/- 32), respectively and these values remained unchanged with nicotine. Significant increases in levels of gastrin, CCK and PP were, however, found with infusions of BBS alone or with BBS in combination with nicotine. Gastrin levels were higher whereas CCK and PP levels were lower with BBS alone than with BBS plus nicotine. The peak values for CCK and PP, but not gastrin, were less during second BBS infusion. These results indicate that nicotine, in presence of bombesin, has an inhibitory effect on the release of gastrin and a stimulatory effect on the release of PP and CCK.     

Plasma lactate, GH and GH-binding protein levels in exercise following BCAA supplementation in athletes

Summary. Branched chain amino acids (BCAA) stimulate protein synthesis, and growth hormone (GH) is a mediator in this process. A pre-exercise BCAA ingestion increases muscle BCAA uptake and use. Therefore after one month of chronic BCAA treatment (0.2 g kg⁻¹ of body weight), the effects of a pre-exercise oral supplementation of BCAA (9.64 g) on the plasma lactate (La) were examined in triathletes, before and after 60 min of physical exercise (75% of VO₂max). The plasma levels of GH (pGH) and of growth hormone binding protein (pGHBP) were also studied. The end-exercise La of each athlete was higher than basal. Furthermore, after the chronic BCAA treatment, these end-exercise levels were lower than before this treatment (8.6 ± 0.8 mmol L⁻¹ after vs 12.8 ± 1.0 mmol L⁻¹ before treatment; p < 0.05 [mean ± std. err.]). The end-exercise pGH of each athlete was higher than basal (p < 0.05). Furthermore, after the chronic treatment, this end-exercise pGH was higher (but not significantly, p = 0.08) than before this treatment (12.2 ± 2.0 ng mL⁻¹ before vs 33.8 ± 13.6 ng mL⁻¹ after treatment). The end-exercise pGHBP was higher than basal (p < 0.05); and after the BCAA chronic treatment, this end-exercise pGHBP was 738 ± 85 pmol L⁻¹ before vs 1691 ± 555 pmol L⁻¹ after. pGH/pGHBP ratio was unchanged in each athlete and between the groups, but a tendency to increase was observed at end-exercise. The lower La at the end of an intense muscular exercise may reflect an improvement of BCAA use, due to the BCAA chronic treatment. The chronic BCAA effects on pGH and pGHBP might suggest an improvement of muscle activity through protein synthesis. Received January 5, 1999 / Accepted June 17, 1999     

Effect of Helicobacter pylori infection on gastric acid secretion and meal-stimulated serum gastrin in children

Background. Comparative studies of gastric acid secretion in children related to Helicobacter pylori infection are lacking. The purpose of this study was to compare acid secretion and meal‐stimulated gastrin in relation to H. pylori infection among pediatric patients. Materials and Methods. Thirty‐six children aged 10–17 years (17 with H. pylori infection) undergoing diagnostic endoscopy participated in the study. Diagnoses included gastritis only (n = 23), duodenal ulcer (n = 5) and normal histology (n = 8). Gastric acid output was studied using the endoscopic gastric secretion test before and 2–3 months after H. pylori eradication. Meal‐stimulated serum gastrin response was assessed before and 12 months after eradication. Results. H. pylori gastritis was typically antrum‐predominant. Acid secretion was greater in H. pylori‐positive patients with duodenal ulcer than in gastritis‐only patients or controls [mean ± standard error (SE): 6.56 ± 1.4, 3.11 ± 0.4 and 2.65 ± 0.2 mEq/10 minutes, respectively; p < .001]. Stimulated acid secretion was higher in H. pylori‐positive boys than girls (5.0 ± 0.8 vs. 2.51 ± 0.4 mEq/10 minutes, respectively; p < .05). Stimulated acid secretion pre‐ and post‐H. pylori eradication was similar (5.47 ± 0.8 vs. 4.67 ± 0.9 mEq/10 minutes, respectively; p = .21). Increased basal and meal‐stimulated gastrin release reversed following H. pylori eradication (e.g. basal from 134 to 46 pg/ml, p < .001 and peak from 544 to 133 pg/ml, p < .05). Conclusions. H. pylori infection in children is associated with a marked but reversible increase in meal‐stimulated serum gastrin release. Gastric acid hypersecretion in duodenal ulcer remains after H. pylori eradication, suggesting that the host factor plays a critical role in outcome of the infection.     

The effects of ammonia on pancreatic enzyme secretion in vivo and in vitro.

BACKGROUND: Recent studies clearly demonstrate that Helicobacter pylori (H. pylori) infection of the stomach causes persistent elevation of ammonia (NH3) in gastric juice leading to hypergastrinemia and enhanced pancreatic enzyme secretion. METHODS: The aim of this study is to evaluate the influence of NH4OH on plasma gastrin level and exocrine pancreatic secretion in vivo in conscious dogs equipped with chronic pancreatic fistulas and on secretory activity of in vitro isolated acini obtained from the rat pancreas by collagenase digestion. The effects of NH4OH on amylase release from pancreatic acini were compared with those produced by simple alkalization of these acini with NaOH. RESULTS: NH4OH given intraduodenally (i.d.) in increasing concentrations (0.5, 1.0, 2.0, 4.0, or 8.0 mM/L) resulted in an increase of pancreatic protein output, reaching respectively 9%, 10%, 19%, 16% and 17% of caerulein maximum in these animals and in a marked increase in plasma gastrin level. NH4OH (8 x 0 mM/L, i.d.) given during intravenous (i.v.) infusion of secretin (50 pmol/kg-h) and cholecystokinin (50 pmol/kg-h) reduced the HCO3 and protein outputs by 35% and 37% respectively, as compared to control obtained with infusion of secretin plus cholecystokinin alone. When pancreatic secretion was stimulated by ordinary feeding the same amount of NH4OH administered i.d. decreased the HCO3- and protein responses by 78% and 47% respectively, and had no significant effect on postprandial plasma gastrin. In isolated pancreatic acini, increasing concentrations of NH4OH (10(-7)-10(-4) M) produced a concentration-dependent stimulation of amylase release, reaching about 43% of caerulein-induced maximum. When various concentrations of NH4OH were added to submaximal concentration of caerulein (10(-12) M) or urecholine (10(-5) M), the enzyme secretion was reduced at a dose 10(-5) M of NH4OH by 38% or 40%, respectively. Simple alkalization with NaOH of the incubation medium up to pH 8.5 markedly stimulated basal amylase secretion from isolated pancreatic acini, whereas the secretory response of these acini to pancreatic secretagogues was significantly diminished by about 30%. LDH release into the incubation medium was not significantly changed in all tests indicating that NH4OH did not produce any apparent damage of pancreatic acini and this was confirmed by histological examination of these acini. CONCLUSIONS: 1. NH4OH affects basal and stimulated pancreatic secretion. 2. The excessive release of gastrin may be responsible for the stimulation of basal pancreatic enzyme secretion in conscious animals, and 3. The inhibitory effects of NH4OH on stimulated secretion might be mediated, at least in part, by its direct action on the isolated pancreatic acini possibly due to the alkalization of these acini.     

Role of histamine H2-receptors in gastric and pancreatic release of somatostatin-like immunoreactivity during the gastric phase of a meal

The present study was designed to determine the role of H₂-receptors in the postprandial release of somatostatin-like immunoreactivity (SLI) from the gastric fundus and antrum and from the pancreas. In dogs subjected to laparotomy, the pylorus was bisected and a gastric fistula was created, following which 250 ml 20% liver extract (LE) at pH 7 or 2 were instilled intragastrically. In the fundic vein the incremental SLI rise in response to LE at pH 7 was 2423 ± 540 pg/ml during a control infusion of saline and 4780 ± 863 pg/ml during the infusion of cimetidine (1 mg/kg per h) (P < 0.05). In the antral vein the incremental SLI in response to LE at pH 7 was 2182 ± 530 pg/ml during the saline control but did not rise significantly during cimetidine infusion. In the pancreatic vein the incremental SLI level after LE at pH 7 was 1953 ± 358 pg/ml in the control experiments and 4430 ± 1024 pg/ml during cimetidine infusion (P < 0.025). The incremental inferior vena cava SLI level was approximately 925 pg/ml in both groups (not significant).The instillation of LE at pH 2 during the saline control lowered fundic vein SLI by 500 pg/ml; this decline was abolished during cimetidine infusion. In the antral vein the incremental SLI level of 15 750 ± 2514 pg/ml during saline was lowered to only 6728 ± 2257 pg/ml during cimetidine (ifP < 0.025). After LE at pH 2 the incremental pancreatic vein SLI level of if5641 ± to be one regulatory component in the modulation of gastric acid secretion and gastrin release [21,26] during the gastric phase of a meal. The possible involvement of H₂-receptors in this regulatory system is schematized in Fig. 7.Pancreatic SLI release is also influenced by H₂-receptors but this appears to depend on the intragastric pH; stimulation of the receptors appears to lower the pancreatic SLI response to neutral protein and raise the response to acidified protein. If these effects are due to stimulation of gastric and/or pancreatic H₂-receptors can not be determined from the present data.These findings, in conjunction with previous studies [21–25], reveal a highly complex regulatory system for somatostin release during the gastric phase of meal, and indicate that, in addition to the influence of muscarinic-cholinergic [23], adrenergic mechanisms [24] and prostaglandins [25], reveal a histaminergic influence must now be recognized.