Search PubMed⌕ Search

Biomedical subjects

H T Debas

Publications and source records attributed to H T Debas.

At least 55 records · Page 3Linked to original sources
PubMed1990

Somatostatin inhibits pancreatic exocrine secretion via a neural mechanism.

The mechanism of inhibition of pancreatic exocrine secretion by somatostatin is unknown. We hypothesized that somatostatin acts indirectly, via intrinsic pancreatic neurons, to inhibit pancreatic exocrine secretion. To test this hypothesis, amylase and volume outputs in response to secretin (10(-8) mol/L) and cholecystokinin octapeptide (CCK) (10(-8) mol/L) were studied in the rat isolated, perfused, pancreas model. Somatostatin (10(-7) mol/L) significantly inhibited amylase output by 48% compared with control (352 +/- 57 v 676 +/- 85 U/30 min, P less than .05 by ANOVA). Blockade of axonal neuronal transmission by tetrodotoxin (10(-7) mol/L) completely abolished the inhibitory effect of somatostatin (992 +/- 53 U/30 min). Similar effects were seen on volume output. The inhibitory effect of somatostatin on amylase output was not affected by cholinergic receptor blockade with atropine (328 +/- 65 U/30 min) or by sympathetic ganglionic blockade with hexamethonium (360 +/- 68 U/30 min). This suggests that the intrinsic pancreatic neurons responsible for the inhibitory effect of somatostatin are peptidergic. The possibility that somatostatin acts directly on the acinar cell to inhibit exocrine secretion was tested by incubating varying doses of somatostatin (10(-12) to 10(-7) mol/L) with isolated pancreatic acini in the presence of graded concentrations of CCK (10(-12) to 10(-10) mol/L). In this model, CCK alone is a potent stimulant of amylase release, with a Km of 6 X 10(-12) mol/L and a Vmax of 22 +/- 3% total amylase. In this model, somatostatin had no inhibitory effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Amylases↗
PubMed1990

Metabolism of enkephalin in stomach wall of rats.

Peptidases degrade neuropeptides and thereby limit the duration and extent of their influence. This investigation examined the importance of peptidases in the degradation of the neuropeptide enkephalin in the stomach wall of the rat. Metabolism of [Leu5]- and [D-Ala2][Leu5]enkephalin by gastric membranes was examined in vitro. Degradation of [Tyr1-3H][Leu5]enkephalin was studied in the gastric submucosa of anesthetized and conscious rats in vivo by using a catheter to deliver peptide to tissues and implanted dialysis fibers to collect the metabolites. Specific inhibitors were used to assess the contribution of particular enzymes. [Leu5]- and [Tyr1-3H][Leu5]enkephalin were metabolized by membranes and in the stomach wall by hydrolysis of the Tyr1-Gly2 bond. Degradation was inhibited by the aminopeptidase inhibitor amastatin (10(-5) M in vitro, 10 nmol in vivo). Inhibitors of endopeptidase-24.11 (phosphoramidon) and angiotensin-converting enzyme (captopril) did not inhibit degradation. Metabolism of the aminopeptidase-resistant analogue [D-Ala2][Leu5]enkephalin by membranes was unaffected by amastatin and weakly inhibited by phosphoramidon affected by amastatin and weakly inhibited by phosphoramidon and captopril. A carboxypeptidase removed the COOH-terminal leucine residue and made a substantial contribution to degradation of both peptides by gastric membranes.

Animals↗
PubMed1990

CGRP stimulates the release of pro-somatostatin-derived peptides from the gastric fundus.

Calcitonin gene-related peptide (CGRP) stimulates release of peptides derived from pro-somatostatin (Pro-S) into the general circulation. The purpose of this investigation was to elucidate the origin and molecular heterogeneity of Pro-S-derived peptides secreted in response to CGRP. Catheters were placed into the vena cava and veins draining the gastric fundus and corpus, antrum, and small intestine of anesthetized pigs. Human CGRP I was infused into the descending aorta at 0.2, 0.4, 0.8, and 1.6 micrograms.kg-1.h-1 for consecutive 30-min intervals. Blood was collected from the venous catheters after each period. S-28 was separated from Pro-S, S-14, and S-13 by immunoaffinity chromatography and peptides were quantified by radioimmunoassay. CGRP primarily evoked release of peptides measured collectively as Pro-S, S-14, and S-13 into venous blood draining the fundus and corpus, and concentrations were significantly elevated above basal at 0.8 and 1.6 micrograms.kg-1.h-1 CGRP (P less than 0.05). Basal concentrations of S-28, Pro-S, S-14, and S-13 in blood from the antrum and small intestine were not significantly elevated by CGRP. In conclusion, CGRP stimulated release of Pro-S-derived peptides from the gastric fundus and corpus but not from the antrum or small intestine.

Animals↗
PubMed1990

Geranyl-geranyl acetone: a novel stimulant of secretin release in the dog.

Geranyl-geranyl acetone (GGA), a new acyclic polyisoprenoid, anti-ulcer drug appears to exert its beneficial effect by stimulating bicarbonate secretion from the stomach and pancreas. Its efficacy in stimulating pancreatic bicarbonate is particularly striking, and this study was designed to examine the mechanism for this action. Since it is structurally similar to the side chain of the prostaglandin molecule, its ability to stimulate bicarbonate secretion could be a direct one. On the other hand, the magnitude of pancreatic bicarbonate response (about 50% of maximal response to secretin) suggests it might act by releasing secretin. Two types of experiments were performed in dogs with pancreatic fistulas: first, secretagogue interactions were examined by studying the effect of intraduodenal GGA (8 mg/kg) or its carrier (control) on the dose-response curves to exogenous secretin and cholecystokinin octapeptide (CCK-8); second, the effect of graded doses of intraduodenal GGA on pancreatic bicarbonate and plasma secretin-like immunoreactivity (SLI) responses was tested directly. Pancreatic bicarbonate responses (micromoles per 30 min) were to secretin doses of 32, 125, and 500 ng/kg/h. Without and with GGA, responses were 74 +/- 27, 952 +/- 215, and 2,000 +/- 425 and 599 +/- 110, 1,624 +/- 472, and 2,129 +/- 398 ng/kg/h, respectively. Similarly, the bicarbonate responses to CCK-8 were augmented. Basal plasma SLI was 1.5 +/- 0.6 pM/ml. Peak plasma SLI in response to 2, 4, and 8 mg of GGA intraduodenally were 6.8 +/- 0.7, 8.9 +/- 3.1, and 19.6 +/- 2.7 pM/ml, respectively. It is concluded that GGA is a potent stimulant of pancreatic bicarbonate secretion, and this action appears to be mediated by the release of duodenal secretin.

Animals↗
PubMed1989

Gastric distension is a physiologic satiety signal in the dog.

Gastric distension is thought to produce satiety, but whether this effect is seen during physiologic distension by food is unknown. The purpose of this study was to determine whether levels of gastric distension seen during a meal have a satiety effect and whether the nutrient value of the meal was important. Four dogs were prepared with gastric, duodenal, and esophageal fistulas. Physiologic distension was determined by allowing the animals to eat liquid nutrient diet until sated and measuring the volume consumed and the time it took to consume it (means 2000 ml in 4 min). To test the effect of gastric distension on satiety, distension was produced during sham feeding by infusions of either liquid nutrient, inert liquid (Karaya), or by a water-filled balloon. Lower degrees of distension were also tested to determine if a dose-response relationship existed. Balloon, inert, and nutrient distension all inhibited sham feeding dose-dependently. Peak inhibitions of sham feeding caused by physiologic gastric distension (balloon, inert, nutrient) were 69 +/- 5%, 67 +/- 12%, and 61 +/- 6%, respectively. In all cases, maximal distension terminated sham feeding before the end of the feeding period. The effect of gastric distension on feeding was not blocked by pretreatment with atropine (50 micrograms/kg). Thus, graded degrees of gastric distension, comparable to those seen during ingestion of a normal meal, produced graded inhibition of food intake by a noncholinergic mechanism and independent of the nutrient properties of the food.

Animal Nutritional Physiological Phenomena↗
PubMed1989

Characterization of in vivo acid secretory responses of rabbit with comparison to dog and rat.

Even though rabbit gastric glands are a commonly used model for the study of gastric physiology, little is known about the secretion of gastric acid in the rabbit in vivo. Gastric acid secretion in response to pentagastrin, histamine, and bethanechol stimulation, and the effect of specific cholinergic and histamine H2-receptor blockers was studied in 62 urethane-anesthetized rabbits. Additionally, the responses of eight conscious rabbits prepared with chronic gastric fistula were compared with similarly prepared conscious dogs (n = 10) and conscious rats (n = 18). In anesthetized rabbits, maximal pentagastrin stimulation resulted in acid outputs only 22% that of maximal histamine stimulation, but this was enhanced by restoring cholinergic tone with a subthreshold infusion of bethanechol. In conscious rabbits, pentagastrin was an effective stimulant, resulting in maximal acid output 70% that of maximal histamine stimulation. This is in contrast to the in vitro findings reported reported by others utilizing isolated gastric glands and cells. Histamine was a potent stimulant of acid secretion in both the anesthetized and conscious rabbit, an observation that parallels the in vitro findings. Unlike the dog and rat, atropine was ineffective as an inhibitor of histamine-stimulated acid secretion in the conscious rabbit, although it was marginally effective against histamine in anesthetized rabbits and against pentagastrin in conscious rabbits. It is concluded that cholinergic tone plays a crucial role in pentagastrin-stimulated acid secretion in the rabbit. This may be an explanation for the poor response to pentagastrin described in isolated rabbit gastric gland preparations.

Animals↗
PubMed1989

Effects of intramural division of gastric vagal fibers on stimulated acid production.

Transmural proximal gastric vagotomy, an experimental procedure designed to denervate the gastric fundus by intramural division of vagal fibers, was evaluated as a means of reducing stimulated gastric acid output. The procedure reduced peak acid output in response to insulin stimulation by 71 percent. Acid production was not further decreased by extramural division of vagal fibers. It also decreased parietal cell sensitivity to pentagastrin stimulation and did not interfere with emptying of a liquid meal. We have concluded that transmural proximal gastric vagotomy is technically straightforward, reliably divides fundic vagal fibers, produces a significant reduction in acid production equivalent to that produced by standard operative techniques, and does not interfere with gastric emptying.

Animals↗
PubMed1989

Cholecystokinin receptor antagonism of stimulated pancreatic and gastric secretion.

The effects of cholecystokinin receptor antagonist, dipentyl-3,4-dichloroproglumide (DDP), on stimulated pancreatic and gastric secretion were studied in the rat. DDP dose-dependently inhibited cholecystokinin-stimulated amylase release from dispersed acinar cells. In vivo, DDP inhibited cholecystokinin octapeptide-stimulated amylase and protein secretion. DDP also inhibited pentagastrin-stimulated gastric acid secretion in vivo. Meal-stimulated acid output was decreased by 34% (DDP 400 micrograms/kg/hr) but responsiveness to histamine or parachlorophenyl-gamma-aminobutyric acid was unchanged.

Amylases↗
PubMed1989

Trophic effect of amniotic fluid on cultured fetal gastric mucosal cells.

This study examines the hypothesis that the growth and development of fetal gastric epithelial cells is critically dependent on the presence of trophic factors in amniotic fluid. Fetal gastric epithelial cells (predominantly parietal cells) were grown in culture in the presence of graded concentrations of rabbit amniotic fluid, fetal bovine serum, or a control solution containing the nutrients specific to amniotic fluid. After 7 days, cells were harvested and growth was assessed by cell counts and DNA contents. Amniotic fluid stimulated growth of these cultured cells with a potency similar to that of fetal bovine serum. Cell growth was significantly enhanced by amniotic fluid at each dose tested, when compared to the appropriate nutrient control group. Cell growth could not be maintained in the absence of amniotic fluid or fetal bovine serum. We conclude that amniotic fluid contains factors which are trophic to the growth of cultured fetal gastric epithelial cells. The nature of these factors remains to be determined.

Amniotic Fluid↗
PubMed1989

Metabolism and inactivation of gastrin releasing peptide by endopeptidase-24.11 in the dog.

The purpose of this investigation was to examine the metabolism and inactivation of gastrin releasing peptide 10 (GRP10) by endopeptidase-24.11 prepared from the stomach wall. GRP10 was metabolized in vitro by gastric endopeptidase-24.11. The metabolites were purified by high-pressure liquid chromatography and identified as (1-8) GRP10 and (9-10) GRP10 by amino acid analysis, indicating hydrolysis of the His8-Leu9 bond. The intravenous administration of GRP10 to conscious dogs stimulated gastrin release, gastric acid secretion, pancreatic protein secretion and pancreatic bicarbonate secretion. Incubation of GRP10 with endopeptidase-24.11 significantly diminished the biological activity of the digests compared to control digests containing heat-inactivated enzyme. This effect was abolished by the enzyme inhibitor phosphoramidon. It is concluded that endopeptidase-24.11 from the stomach metabolizes and inactivates GRP10.

Animals↗
PubMed1989

Inhibition of gastric and pancreatic secretion in dogs by CGRP: role of somatostatin.

The coexistence of calcitonin gene-related peptide (CGRP) and somatostatin (SS) within the stomach and pancreas and the potent inhibitory effects of both peptides on exocrine secretions from these organs suggest that they are functionally related. To assess the potential role of SS in the mediation of CGRP action, the effects of intravenous human CGRP (64, 132, and 264 pmol.kg-1.h-1) and somatostatin-14 (SS-14; 100, 400, and 800 pmol.kg-1.h-1) on plasma levels of SS immunoreactivity (SS-IR) and on pentagastrin-stimulated gastric and pancreatic secretion were compared in conscious dogs. CGRP caused significant inhibition of gastric acid (85-102%), pancreatic protein (63-86%), and pancreatic bicarbonate (74-89%) outputs and a simultaneous dose-related rise (40-102 fmol/ml) in plasma SS-IR. Cessation of CGRP infusion resulted in prompt return of plasma SS-IR to basal levels and an increase in gastric and pancreatic secretion. Although CGRP is a potent releasor of SS into the circulation, its inhibitory action on gastric acid secretion cannot be explained solely by a rise in plasma SS-IR. In the pancreas, in contrast to the stomach, inhibition appears to be more closely related to a rise in circulating level of SS-IR.

Animals↗
PubMed1989

Management of severe acute pancreatitis: an evolving approach.

No major breakthrough has occurred in our understanding of the etiology or pathogenesis of acute pancreatitis. However, significant advances in management of the disease have resulted in improved survival. These include disease severity assessment by Ranson's criteria or by similar other clinical methods, as well as by computerized tomography (CT). The use of contrast-enhanced CT has made possible early diagnosis of pancreatic necrosis by showing areas of hypoperfusion. Once the presence of necrosis is established, CT-guided needle aspiration of necrotic tissue can be performed for gram stain and for culture of bacteria. This approach makes possible earlier diagnosis of pancreatic sepsis, and hence earlier surgery. Other important contributions have been radiologic and endoscopic interventional techniques. Percutaneous catheter drainage of rapidly enlarging acute pseudocysts can obviate the serious complication of free rupture of pseudocysts into the peritoneal cavity; similar drainage of infected pseudocysts may also provide a definitive or at least a palliative therapy. Bleeding from eroded vessels, false aneurysms or pseudocysts can often be successfully controlled by selective angiography. In severe acute biliary pancreatitis, endoscopic sphincterotomy within 72 hours of admission has been shown to reduce morbidity, mortality, and hospital stay. These interventional techniques permit surgery to be postponed until the most optimal time. The advances cited above, as well as improved intensive care and nutritional management, are beginning to reduce the high mortality of severe acute pancreatitis.

Acute Disease↗
PubMed1989

Ontogeny of the smooth muscle response to histamine in rabbit and human small bowel.

Histamine is known to stimulate small bowel smooth muscle contraction in adults. We studied the response to histamine of small bowel from 27 day gestation fetal (term = 31 days), 4 days-old neonatal, and weanling rabbits using an isolated muscle strip technique in vitro. Sensitivity to histamine stimulation decreased with increasing age, with a six-fold difference in mean D50 between fetal and weanling bowel. A strong contractile response was also obtained in human fetal bowel between 16 and 24 weeks gestation. The response to histamine was inhibited at all ages in both rabbit and human bowel by specific histamine H1 receptor blockade with diphenhydramine, and not by H2 or cholinergic receptor blockers. We conclude that histamine stimulates rabbit and human fetal small bowel contraction; stimulation specifically occurs via the histamine H1 receptor, and is unrelated to release of acetylcholine; sensitivity to histamine decreases significantly with maturity in the rabbit.

Animals↗
PubMed1989

A simplified technique for rapid truncal vagotomy.

A technique of truncal vagotomy is described that allows for rapid identification of the vagal trunks based on consistent anatomic relationships. The technique requires neither esophageal mobilization nor extensive dissection. Vagotomy is performed under direct vision and with precision.

Humans↗
PubMed1988

Postprandial neurohormonal control of gastric emptying.

The delay in gastric emptying after a meal is thought to result from nutrient distention-induced release of peptides and neurotransmitters in the gut. The potential contribution of the brain and central neuropeptides to the postprandial regulation of gastric emptying has not been studied adequately. The purpose of this study was twofold: to examine the relative importance and pure central stimulation (sham feeding) or pure peripheral stimulation (duodenal feeding) on gastric emptying, and to determine whether relevant neuropeptides act in the brain to slow gastric emptying of a meal. Six mongrel dogs were prepared with esophageal fistulas, gastric fistulas, duodenal fistulas, and chronic lateral cerebroventricular guides. Gastric emptying of a 300 ml saline solution meal was measured by a phenol red dye dilution technique. Sham feeding of a blenderized meal through the esophageal fistula was used as a central cephalic stimulus. Intraduodenal oleic acid was used as a peripheral stimulus. Both sham feeding and intraduodenal oleic acid inhibited gastric emptying by 59 +/- 12 percent, 73 +/- 5 percent, respectively. In separate studies, we examined the effect on gastric emptying of a bolus injection into the lateral cerebral ventricle of graded doses of corticotropin-releasing factor (110 to 440 pmol/kg), cholecystokinin (16 to 128 pmol/kg), somatostatin-14 (55 pmol/kg), human calcitonin gene-related peptide (230 pmol/kg), and neuropeptide Y (62 to 250 pmol/kg). These peptides are known to affect satiety, gastric emptying, and gastric acid secretion. Of these, only neuropeptide Y and cholecystokinin had an effect on gastric emptying when administered into the lateral cerebral ventricle. Neuropeptide Y inhibited emptying by 28 +/- 8 percent and cholecystokinin accelerated emptying by 32 +/- 12 percent (p less than 0.05). Sham feeding inhibits gastric emptying to a similar degree as intraduodenal feeding, and of the neuropeptides tested, only neuropeptide Y inhibited gastric emptying when given into the brain. The central release of neuropeptides such as neuropeptide Y during a meal may trigger neural pathways that promote postprandial delay in gastric emptying. Central signals may be as important as peripheral signals in the postprandial control of gastric emptying. Further studies are needed to determine the mechanism by which sham feeding inhibits gastric emptying and whether central release of neuropeptide Y is involved.

Animals↗
PubMed1988

The effect of somatostatin on experimental intestinal obstruction.

The effect of somatostatin (SS-14) was tested in an anesthetized rabbit model of closed-loop ileal obstruction. Experimental groups included (1) immediate treatment (N = 6) receiving SS-14 2,000 pmol X kg-1 X h-1 intravenously (I.V.) beginning at the time of ileal obstruction, (2) delayed treatment (N = 5) receiving SS-14 beginning 6 hours following ileal obstruction, and (3) control (N = 6) receiving only hydration. After 24 hours, all rabbits were killed. Significantly decreased intestinal luminal volume and sodium and potassium output was observed with both immediate and delayed SS-14 treatment when compared to control. Additionally, the gross and microscopic pathologic features of intestinal distension, inflammation, and necrosis seen in control rabbits were absent in rabbits treated with SS-14. The known broad spectrum of physiologic activity of SS-14 on the gastrointestinal tract appeared beneficial in this rabbit model of intestinal obstruction.

Animals↗