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Biomedical subjects

J H Walsh

Publications and source records attributed to J H Walsh.

At least 19 recordsLinked to original sources
PubMed1992

Intestinal acid inhibits gastric acid secretion by neural and hormonal mechanisms in rats.

To determine the relative contributions of neural reflexes and intestinal hormones to the inhibition of gastric acid secretion by intestinal acidification, rats with an extrinsically denervated, transplanted segment of jejunum, and those with an innervated segment of jejunum, were studied. Postoperatively, meal-stimulated gastric acid secretion was measured. When the acid secretory response to intragastric liver extract reached a plateau, graded concentrations of hydrochloric acid or saline were instilled into the jejunal segments. Gastric acid secretion was inhibited by intrajejunal acid (pH 2.5) by 79% in the innervated rats and by 64% in the transplanted group. Thus at a pH of 2.5 there was a 15% greater maximum inhibition of plateau acid response in the innervated rats than in the transplanted rats, presumably because of the extrinsic neural contribution. To examine the hormonal mediators, the effects of a somatostatin monoclonal antibody and a CCK-A receptor antagonist (L 364718) on acid-induced inhibition of gastric acid secretion were studied in transplanted rats. Treatment with a somatostatin monoclonal antibody or with L 364718 reduced the acid-induced (pH 2.5) inhibition of gastric acid secretion by 93 and 27%, respectively. Jejunal acidification inhibits gastric acid secretion in the rat by both neural and hormonal mechanisms. The hormonal mechanism is mediated by somatostatin and CCK.

Acids↗
PubMed1992

Role of gastrin, histamine, and acetylcholine in the gastric phase of acid secretion in anesthetized rats.

To determine the relative contributions of gastrin, histamine, and cholinergic stimulation to the gastric phase of acid secretion, peptone-stimulated acid output was measured in urethan-anesthetized pylorus-ligated rats after intravenous administration of gastrin monoclonal antibody, cimetidine, and atropine. Intragastric peptone stimulated acid secretion four-fold over basal, which was associated with a significant increase in plasma gastrin levels. Gastrin immunoneutralization and simultaneous H2- and muscarinic-receptor blockade demonstrated that approximately 40% of peptone-stimulated acid output as attributed to endogenous gastrin through a histamine-dependent pathway, whereas 20% of acid output was accounted for by a cholinergic component. Another 10% of titratable acid was omeprazole-insensitive and presumably due to intragastric digestion of peptone. Therefore, approximately 30% residual acid output in response to peptone could not be accounted for by known acid stimulatory mechanisms. In rats given somatostatin monoclonal antibody to block the tonic inhibitory effect of endogenous somatostatin, residual acid output was a similar fraction of meal-stimulated acid output. In contrast, gastric distension induced by intragastric instillation of saline stimulated acid secretion to 1.5-fold over basal. Although 60% of distension-induced acid secretion could be inhibited by either H2 blockade or gastrin immunoneutralization, acid output returned to basal levels after simultaneous muscarinic blockade. These results indicate that gastrin, through a histaminergic pathway, is the principal mediator of meal-stimulated acid secretion in anesthetized rats. Approximately 30% of acid output was due to other unidentified mechanisms, such as chemical secretagogues, a direct effect of amino acids, or novel peptides.

Acetylcholine↗
PubMed1979

Duodenal-ulcer disease associated with elevated serum pepsinogen I: an inherited autosomal dominant disorder.

To delineate genetic factors involved in the pathogenesis of duodenal ulcer, serum pepsinogen I levels were determined by radioimmunoassay in two large kindreds with multiple members affected with duodenal ulcer. An elevated serum immunoreactive pepsinogen I concentration (greater than 100 ng per milliliter) segregated as an autosomal dominant trait in these families. Furthermore, 10 of 11 patients with clinical ulcer disease in these families had hyperpepsinogenemia. An elevated serum pepsinogen I concentration appears to be a subclinical marker of the ulcer diathesis in families with this autosomal dominant form of peptic-ulcer disease.

Duodenal Ulcer↗
PubMed1979

The avian proventriculus is an abundant source of endocrine cells with bombesin-like immunoreactivity.

Radioimmunoassays using specific bombesin antisera revealed high concentrations of immunoreactivity in the turkey proventriculus, and negligible amounts of activity elsewhere in the gut. In immunohistochemical studies the same antisera revealed abundant endocrine-like cells in proventriculus mucosa, and isolated cells in small intestinal mucosa. In contrast to the rat, immunoreactivity was not demonstrated in nerves.

Animals↗
PubMed1979

Pancreatic polypeptide response in patients with chronic pancreatitis.

We studied the plasma pancreatic polypeptide (PP) response to a meal in patients with pancreatitis and attempted to correlate the PP increment with the degree of pancreatic exocrine insufficiency. Control subjects and patients with recurrent pancreatitis showed significant mean increase (P less than 0.05) in plasma PP concentration in response to food. By contrast chronic pancreatitis patients had no significant increase in plasma PP. However, some subjects with normal pancreatic had no response and some patients with chronic pancreatitis did show a response. In addition, no correlation was observed between the PP response and pancreatic exocrine secretion. We conclude that the PP response to a meal has only limited value in the detection of pancreatic destruction.

Adult↗
PubMed1979

Regulation of gastric acid secretion.

The three stimulants of gastric acid secretion likely to have physiological roles in regulation of secretion are acetylcholine, gastrin, and histamine. Acetylcholine is released by vagal and intramucosal reflex stimulation, acting directly on the parietal cell. Gastrin is released by peptides and free amino acids in the stomach and is the only known hormonal stimulant of acid secretion. Release of gastrin by acetylcholine may occur. However, cholinergic control of gastrin release is complex since under certain conditions anticholinergic drugs may actually enhance gastrin release. Factors regulating histamine release have not been defined, but studies with H2-receptor antagonists leave little doubt that histamine has an important role in acid secretion. Studies with isolated parietal cells indicate that histamine, gastrin, and acetylcholine each appear to act at separate receptors on the parietal cell. Anticholinergic agents specifically prevent the cellular actions of acetylcholine, cimetidine specifically inhibits stimulation by histamine, and neither inhibitor blocks the small direct response to gastrin. Furthermore potentiating interactions occur between histamine, gastrin, and cholinergic agents which may account for the interdependence of secretagogue action observed in vivo. Direct potentiating interactions occur between histamine and gastrin and histamine and carbachol but not between carbachol and gastrin. However, in the presence of histamine, carbachol, and gastrin, a three-way potentiation does occur. By interfering with the potentiating interactions between stimulants, anticholinergic agents and cimetidine display an apparent cross-specificity in vitro that resembles the effects of these agents in intact mucosa. The mechanisms underlying these interactions are unknown, but the actions of histamine appear to be mediated through increased production of cyclic AMP and cyclic AMP analogs, which mimic the interactions involving histamine itself. The secondary effectors for acetylcholine and gastrin and the mechanisms for amplification of the response to combinations of stimulants remain to be elucidated.

Acetylcholine↗
PubMed1979

Effect of atropine on vagal release of gastrin and pancreatic polypeptide.

We studied the effect of several doses of atropine on the serum gastrin and pancreatic polypeptide responses to vagal stimulation in healthy human subjects. Vagal stimulation was induced by sham feeding. To eliminate the effect of gastric acidity on gastrin release, gastric pH was held constant (pH 5) and acid secretion was measured by intragastric titration. Although a small dose of atropine (2.3 mug/kg) significantly inhibited the acid secretory response and completely abolished the pancreatic polypeptide response to sham feeding, this dose of atropine significantly enhanced the gastrin response. Higher atropine doses (7.0 and 21.0 mug/kg) had effects on gastrin and pancreatic polypeptide release which were similar to the 2.3-mug/kg dose. Atropine (0.78 and 2.3 mug/kg) without sham feeding significantly inhibited basal acid secretion and also led to significant increases in serum gastrin above basal levels. The gastrin response to sham feeding with 2.3 mug/kg atropine was significantly greater than the sum of the gastrin responses to sham feeding alone and to 2.3 mug/kg atropine alone, indicating potentiation of vagal gastrin release by atropine. We conclude: (a) Unlike vagally mediated gastric acid secretion and pancreatic polypeptide release which can be blocked by atropine, vagal gastrin release is potentiated by atropine. This observation suggests the existence of a vagal-cholinergic pathway which normally (i.e., in the absence of atropine) inhibits gastrin release. (b) Because atropine (without sham feeding) increased basal gastrin levels, it is likely that the cholinergic pathway which inhibits gastrin release is active even when the vagus nerve is not stimulated by sham feeding.

Adult↗
PubMed1979

Effect of selective proximal vagotomy on food-stimulated gastric acid secretion and gastrin release in patients with duodenal ulcer.

We studied effects of selective proximal vagotomy on food-stimulated acid secretion and gastrin release in 7 duodenal ulcer patients. Food-stimulated acid secretion was evaluated by sham feeding patients and by infusing food directly into their stomachs. Vagotomy reduced sham feeding-stimulated acid secretion from 28.2 +/- 4.6 to 1.2 +/- 0.7 meq/hr (95% reduction) whereas infused food-stimulated secretion was decreased from 36.1 +/- 4.6 to 17.9 +/- 5.5 meq/hr (50% reduction). In contrast to the reductions in acid secretion, the gastrin response to infused food doubled after surgery. Although selective proximal vagotomy reduced the rate of acid secretion in response to infused food and also reduced by 64% the peak secretory capacity (peak acid output to pentagastrin), fractional secretion (i.e., the secretion rate in response to infused food expressed as a percentage of the peak secretory capacity) increased significantly after vagotomy from 63 +/- 7% to 91 +/- 11%. This increased fractional secretion in response to infused food was probably a result of exaggerated gastrin release after vagotomy.

Adult↗
PubMed1979

Evidence that the cholinergic enteropancreatic reflex may be independent of cholecystokinin release.

Studies were performed in four dogs with chronic gastric and pancreatic fistulas following intraduodenal perfusion with 10 mmole hr-1 of sodium oleate for 30 minutes. Radioimmunoassay (RIA) of plasma CCK LI was undertaken by an RIA method using labeled, desulfated CCK 8 I125 and an antiserum raised to CCK 8. The detection limit for the assay was 0.25 to 0.5 fmole and the lowest detectable plasma level was 5 to 10 fmoles ml-1. Since there was equal cross-reactivity to gastrin, a gastrin-specific assay also was employed to evaluate any changes in gastrin levels. After oleate infusion the plasma CCK increment above basal was 50 +/- 11 fmoles ml-1, with return to basal levels after 60 minutes. Administration of atropine significantly (P less than 0.01) inhibited the release of CCK in the first 20 minutes. Thereafter CCK release was not reduced. Plasma gastrin values did not change before and after oleate perfusion. Pancreatic protein output increased from 72 +/- 12 to 420 +/- 55 mg/10 min-1 after oleate administration. However, after atropinization the rise in pancreatic protein output was significantly lower (152 +/- 36 mg/10 min-1) (P less than 0.01). We have shown that, using our RIA method, there is a measurable rise in plasma CCK LI after intraduodenal oleate. After atropinization the CCK response was decreased significantly during the first 30 minutes, but was virtually unchanged during the second 30 minutes, when the fall in pancreatic protein output was most marked. We conclude that the cholinergic mechanism which plays a role in the endogenous stimulation of pancreatic protein secretion by intraduodenal oleate cannot be explained simply be decreased CCK release. This mechanism may be hormonal, distinct from secretin, or neural possibly, via activation of an enteropancreatic reflex.

Animals↗
PubMed1979

Pancreatic polypeptide. Metabolism and effect on pancreatic secretion in dogs.

In dogs with gastric and pancreatic fistulas, porcine pancreatic polypeptide (PP) was infused intravenously in doses of 50, 100, 200, 400, and 800 pmol kg-1 hr-1 in the basal state and in doses of 100, 200, and 400 pmol kg-1 hr-1 during stimulation with submaximal doses of secretin (125 ng kg-1 hr-1) plus caerulein (50 ng kg-1 hr-1). Plasma concentrations of PP were measured by radioimmunoassay, and pancreatic bicarbonate and protein outputs were monitored. The half-time for disappearance of PP was 5.5 +/- 1.0 min, the metabolic clearance rate was 25.6 +/- 1.0 ml kg-1, and the volume of distribution was 209 +/- 42 ml kg-1. Basal pancreatic flow and protein output were significantly inhibited by the lowest dose of PP tested, 50 pmol kg-1 hr-1. The lowest dose of PP significantly inhibiting stimulated pancreatic secretion was 100 pmol kg-1 hr-1 for bicarbonate output and 200 pmol kg-1 hr-1 for protein output. The mean +/- SE peak increment in PP concentration in response to a meal of meat, 210 +/- 39 pM, was greater than the mean peak increment with the 400 pmol kg-1 hr-1 dose of exogenous PP, 175 +/- 19 PM. We conclude that exogenous doses of PP that produce smaller increments in PP concentration than those seen after feeding inhibit pancreatic bicarbonate and protein secretion stimulated by secretin and caerulein. This suggests that the amount of PP released by a meal is sufficient to inhibit pancreatic secretion.

Animals↗
PubMed1979

Bombesin-like peptides in mammals.

Acid extracts of rat gut and brain contain substances that cross-react in a radioimmunoassay for the amphibian skin tetradecapeptide bombesin. Highest concentrations are present in the fundic part of the stomach, but there are significant amounts throughout the small and large intestine. Concentrations in the brain are highest in the hypothalamus. On gel filtration the rat bombesin-like immunoreactivity eluted as two major peaks. Fractionation of the second peak on cation exchange chromatography resolves this material into two further components. Intravenous infusions of partially purified preparations of the two components separated on gel filtration cause increases in serum gastrin in rats that are similar to those produced by immunochemically comparable amounts of synthetic bombesin.

Amino Acid Sequence↗
PubMed1978

Is pancreatic polypeptide a marker for Zollinger-Ellison syndrome?

Basal human pancreatic polypeptide (H.P.P.) concentrations have been measured in 41 pateints with Zollinger-Ellison syndrome (Z.E.S.) and in 100 controls. Basal H.P.P. concentrations in controls varied widely from less than 8 pmol/l (assay detection limit) to 313 pmol/l. In controls, but not in the Z.E.S. patients, there was a highly significant positive correlation between basal H.P.P. and age (P less than 0.01). 4 of the Z.E.S. patients (9.8%) and 3 of the controls (3%) had H.P.P. concentrations over 240 pmol/l. These findings indicate that raised basal H.P.P. concentration is an infrequent finding in patients with gastrinomas and therefore it is not a useful tumour marker.

Adult↗