Biomedical subjects

T E Adrian

Publications and source records attributed to T E Adrian.

At least 145 records · Page 8Linked to original sources

PubMed1990

Intra-ocular transplantation of carcinoid tumours from mastomys and humans.

Carcinoid tumours from man and Mastomys (Praomys) natalensis produce a variety of peptide hormones. The study of these peptide-secreting tumours has been difficult because of the small amount of tissue available and because of limitations with present cell culture systems. The aim of this study was to establish an experimental model where carcinoid tumours could be maintained and their hormone secretion studied. The intra-ocular transplantation technique was chosen for its simplicity and high rate of success. Gastric carcinoid tumours from mastomys (n = 4) and human carcinoids (n = 2) (one bronchial and one ileal) were transplanted to the anterior eye chamber of Sprague-Dawley rats. Pieces of fresh tumour tissue were injected into the anterior eye chamber of rats and allowed to grow for 4-8 weeks. Rats transplanted with human tissue were immunosuppressed by daily injections with cyclosporin A (20 mg/kg). Eye chambers were inspected regularly and plasma from transplanted rats was collected for assay of peptide YY (PYY) and glucagon. Vascularization of transplants occurred within 1-2 days after transplantation in 70-80 per cent of all experiments. Microscopic analysis of transplants demonstrated a rich supply of blood vessels to tumour cells which contained characteristic neurosecretory granules. Transplanted rats had significantly (P less than 0.05) elevated levels of PYY (44-165 pmol/l) and glucagon (67-162 pmol/l) in plasma as compared with sham-operated rats (PYY 28-40 pmol/l, glucagon 33-40 pmol/l), indicating that hormone secretion by tumour cells in oculo was maintained.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Pepsinogen release and acid secretion from human and guinea pig gastric mucosa compromised by hypoxia, endotoxin, or critical illness.

Despite blockade and neutralization of gastric acid, acute gastric lesions cause substantial morbidity and mortality in critically ill patients. Pepsinogen release in response to noxious stimuli such as hypoxia and endotoxin might contribute to mucosal damage. Guinea pig fundic mucosa was mounted in Ussing chambers. Acid secretion, pepsinogen release, potential difference (PD), and resistance were monitored. Gassing with room air or nitrogen diminished acid secretion and PD but increased pepsinogen release 9.7- and 15.5-fold, respectively (both p less than 0.001). Similarly, endotoxin (0.01 and 0.1 units/ml) dose-dependently inhibited acid secretion and PD but increased pepsinogen release 3.3- and 6.1-fold (both p less than 0.05). Endotoxic and air-gassed tissues were edematous with scattered cellular damage by light and transmission electron microscopy; nitrogen-exposed membranes appeared necrotic. Pepsin release may therefore have resulted from cell damage rather than exocytosis. Intragastric peptic activity in critically ill H2-receptor-blocked patients (n = 20) was 5490 +/- 1701 U/ml. The gastric juice of H2-blocked convalescing surgical patients (n = 20) contained 315 +/- 101 U/ml (p less than 0.0001). Occult blood correlated with intragastric peptic activity (r = 0.59, p less than 0.0001) but not with gastric pH (r = 0.04, p = 0.6). These data suggest that the complex of pathophysiologic abnormalities common in critical illness causes substantial pepsin release. Efflux of this potent mucolytic barrier breaker may damage gastric mucosa in severely stressed patients.

Animals↗

PubMed1990

Effects of cholecystokinin and cholinergic receptor blockade on guinea pig pepsinogen secretion.

Although cholecystokinin (CCK) has been reported to stimulate pepsinogen secretion, this action has been poorly characterized. To assess the ability of CCK to regulate mammalian pepsinogen secretion, guinea pig fundic mucosa was incubated in Ussing chambers with CCK-8, carbamylcholine, and pentagastrin, and with cholinergic and CCK antagonists. CCK-8 stimulated pepsinogen secretion at 10(-10) M, with an ED50 of 10(-9) M and maximally (26-fold over basal) at 10(-8) M. Carbachol stimulated pepsinogen and acid secretion with an ED50 of 3 x 10(-7) M and maximally at 10(-6) M. Pentagastrin (10(-9) M-10(-6) M) did not affect acid or pepsinogen secretion, whereas gastrin-I (10(-6) M) stimulated acid secretion slightly but did not alter pepsinogen secretion. L364, 718 (10(-5) M), a specific CCK peripheral receptor antagonist, abolished all pepsigogic effects of 3 x 10(-9) M CCK-8 without altering basal acid or pepsinogen secretion or mucosal electric characteristics. L364,718-treated tissues unresponsive to CCK-8 nevertheless secreted pepsinogen and acid in response to 3 x 10(-7) M carbachol identically to control carbachol-treated preparations. Atropine (10(-5) M) blocked the response to 3 x 10(-7) M carbachol without inhibiting 10(-9) M CCK stimulation. These results support a specific receptor-mediated role for cholecystokinin in the physiologic regulation of guinea pig pepsinogen secretion.

Animals↗

PubMed1990

A novel micromethod for pancreatic acinar secretion. Time course of CCK stimulation and its inhibition by L-364,718.

Dispersed acini have proven to be particularly valuable in the study of pancreatic enzyme secretion. Complex time course studies or experiments requiring large numbers of replicates have proven difficult, however, with currently available techniques. Using a custom-designed incubation chamber, a miniaturized incubation method has been devised, which allows for continuous oxygenation of acini in 96-well microtiter plates and rapid separation of medium from acini by vacuum filtration. The filtrates from individual wells are collected into the wells of a second microtiter plate for pancreatic enzyme measurement. Using the above method, the dose response and time course of cholecystokinin (CCK-8)-stimulated amylase secretion was investigated. During a 1-h incubation, unstimulated amylase secretion was 4.1 +/- 0.3% of total acini content. Response to CCK was very sensitive, being detected at 10(-13) M (p less than 0.05), half-maximal at 10(-11) M CCK (14.0 +/- 0.6%, p less than 0.001) and maximal at 10(-9) M CCK (24.8 +/- 1.0%, p less than 0.001). In the time course experiments, an increase in amylase secretion was detected by 2.5 min and continued to increase steadily to a plateau at 40 min, with both submaximal (10(-11) M) and maximal (10(-9) M) CCK concentrations. The potent and specific CCK-receptor antagonist, L-364,718, caused a dose-dependent decrease in CCK-stimulated amylase secretion, with a half-maximal effect at 10(-10) M. The receptor antagonist, L-364,718, at 10(-8) M completely abolished CCK-stimulated amylase secretion. This microtechnique provides a simple, reliable, and reproducible method for the study of dispersed pancreatic acini.(ABSTRACT TRUNCATED AT 250 WORDS)

Amylases↗

PubMed1989

A micromethod for the assay of cellular secretory physiology: application to rabbit parietal cells.

A micromethod for investigating secretory physiology in isolated cells was evaluated. The method utilized a specially designed polycarbonate incubation chamber to provide constant oxygenation to cells incubating in a 96-well microtiter plate. Cells were rapidly separated from media by vacuum filtration. Isolated parietal cells were utilized to demonstrate the versatility of the method for assay of intracellular accumulation of [14C]-aminopyrine, secretion of intrinsic factor into the medium, and assay of intracellular cAMP. Histamine stimulated the uptake of [14C]aminopyrine and intrinsic factor secretion in a sustained and linear fashion. At the end of the 2-h period uptake of aminopyrine and secretion of intrinsic factor were increased 17- and 5-fold, respectively. This response to histamine was accompanied by a rapid and sustained 3-fold rise in intracellular cyclic AMP. In contrast, carbamylcholine caused a transient increase in [14C]aminopyrine accumulation and intrinsic factor secretion which was most pronounced during the first 10 min and had almost ceased by 30 min. Carbamylcholine had no effect on intracellular cAMP levels. This new method, which can handle 400 replicates using parietal cells from the fundic mucosa of a single rabbit, is suitable for studying the time course of intracellular events which accompany general secretory processes.

Aminopyrine↗

PubMed1989

Cholecystokinin augmentation of 'surgical' pancreatitis. Benefits of receptor blockade.

The management of acute pancreatitis has not changed appreciably throughout several decades. Recent evidence has suggested that cholecystokinin (CCK) may play an important role in pancreatic disease. Investigations into the precise role of CCK in acute pancreatitis have been hampered by the lack of a specific CCK receptor antagonist. Using a newly described, highly potent and specific CCK receptor antagonist, L-364,718, the effect of CCK in two models of acute "surgical" pancreatitis was examined: (1) the bile salt ductal perfusion model in the rat and (2) a traumatic model in the guinea pig. At a suboptimal dose for pancreatic enzyme secretion (25 pmol/kg/h), CCK was found to potentiate the severity of the ensuing pancreatitis in both models. Continuous CCK receptor blockade with L-364,718 (25 nmol/kg/h) improved biochemical, morphologic, and survival indexes. This study suggests that physiologic levels of CCK play an important permissive role in the evolution of acute pancreatitis. The use of L-364,718 as an investigative probe or therapeutic tool for acute pancreatitis is worthy of further consideration.

Acute Disease↗

PubMed1989

Intramural distribution of immunoreactive vasoactive intestinal polypeptide (VIP), substance P, somatostatin and mammalian bombesin in the oesophago-gastro-pyloric region of the human gut.

The intramural distribution of vasoactive intestinal polypeptide (VIP), substance P, somatostatin and mammalian bombesin was studied in the oesophago-gastro-pyloric region of the human gut. At each of 21 sampling sites encompassing this entire area, the gut wall was separated into mucosa, submucosa and muscularis externa, and extracted for radioimmunoassay. VIP levels in the mucosa were very high in the proximal oesophagus (1231 +/- 174 pmol/g, mean +/- SEM) and showed varied, but generally decreasing concentrations towards the stomach, followed by a clear-cut increase across the pyloric canal (distal antrum: 73 +/- 16 pmol/g, proximal duodenum: 366 +/- 62 pmol/g); consistent levels were found in submucosa and muscle (200-400 pmol/g) at most sites, the stomach again showing lower concentrations. By contrast, substance P was present in small amounts as far as the proximal stomach, but sharply increased across the pyloric canal, especially in mucosa and submucosa (distal antrum: 20 +/- 6.5 and 5.5 +/- 1.3 pmol/g; proximal duodenum: 62 +/- 8.5 and 34 +/- 11 pmol/g, respectively). Somatostatin concentrations were very low in the mucosa of the oesophagus and stepwise increased in the cardiac, mid-gastric and pyloric mucosa (cardia: 224 +/- 72 pmol/g; distal antrum: 513 +/- 152 pmol/g; proximal duodenum: 1013 +/- 113 pmol/g); concentrations in the submucosa and muscularis were generally low, with the exception of antrum and duodenum. Mammalian bombesin was comparatively well represented throughout the oesophageal muscularis (5-8 pmol/g), but most abundant in the stomach in all layers (oxyntic mucosa: 24 +/- 2.7 pmol/g; submucosa: 20 +/- 5.7 pmol/g; muscle: 28 +/- 5.0 pmol/g).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1989

Regional differences in concentrations of regulatory peptides in human colon mucosal biopsy.

The study was undertaken to examine regional differences in the concentrations of five regulatory peptides in the human colonic mucosa. Biopsies were obtained during routine colonoscopy from 33 patients whose colonic mucosa was macroscopically and histologically normal. Regulatory peptides were extracted, and measured by specific radioimmunoassays. Concentrations of three peptides that are present predominantly in endocrine cells within colonic mucosa increased significantly towards the rectum: Mean concentrations of peptide YY, enteroglucagon, and somatostatin were about three times greater in the rectum than in the cecum. However, concentrations of two peptides that are present in mucosal nerve fibers diminished significantly towards the rectum: Mean rectal concentrations of vasoactive intestinal peptide and peptide histidine methionine were both about 0.6 of mean cecal concentrations. Concentrations of all five peptides were lower in biopsies taken from colonic polyps than in normal colonic mucosa. Regional differences in colonic mucosal concentrations of regulatory peptides probably reflect differences in the physiological functions of different parts of the colon.

Adolescent↗

PubMed1989

Does vasoactive intestinal polypeptide mediate the pathophysiology of bowel obstruction?

We hypothesized that bioactive peptides might be released into the portal circulation and mediate pathophysiologic alterations accompanying small bowel obstruction. We studied this question in a subacute canine small bowel obstruction model using 50 percent diameter occlusion. Control animals underwent sham laparotomy. Vasoactive intestinal peptide (VIP), peptide YY, and gastrin were measured in portal and systemic plasma by specific radioimmunoassays at 24-hour intervals as the obstruction progressed to completion over 5 days. All peptides in both groups demonstrated portal and peripheral gradients. In control dogs, peptide concentrations did not change postoperatively but VIP increased markedly in obstructed dogs, demonstrating a median portal level of 95 pmol/liter at 96 hours compared with 31.5 pmol/liter in control animals. These portal VIP levels are known to cause hypersecretion and splanchnic vasodilation in experimental models. The release of vasoactive compounds such as VIP may mediate local pathophysiology in human small bowel obstruction. A similar explanation of the systemic effects is consistent with the known cardiopulmonary bioactivity of VIP.

Animals↗

PubMed1989

Decreased parietal cell secretory capacity following vagotomy and pyloroplasty.

Although vagotomy reduces acid secretion in vivo, the effects of vagotomy at the level of the parietal cell are not known. In the present study we examined the in vitro secretory characteristics of parietal cells in rabbits 8 weeks following vagotomy compared to unoperated and sham-operated controls. Acid secretion was assessed by the uptake of [14C]aminopyrine (AP) in isolated gastric glands. Also, gastric fundus histology, mucosal thickness, parietal cell density, and gastric gland somatostatin content were examined. Basal AP uptake was decreased following vagotomy (8 +/- 0.4 pmole/mg dry wt) compared to controls (21 +/- 2) (P less than 0.001). Increase in AP uptake by the cholinergic agonist carbachol was unaffected after vagotomy (P greater than 0.5) suggesting intact muscarinic receptors and calcium second messenger system. Increase in AP uptake was significantly reduced following vagotomy by the cyclic AMP-mediated agonist histamine (P less than 0.05) and the cyclic AMP mimetic 8-bromo cyclic AMP (P less than 0.001) suggesting an alteration in the ability of the parietal cell to utilize cAMP following vagotomy. There were no discernible differences in histology, mucosal thickness, or parietal cell number in vagotomized animals compared to controls (P greater than 0.5). There was a significant increase in gastric gland somatostatin content following vagotomy (37 +/- 10 fmole/mg dry wt) compared to control (14 +/- 1.5) (P = 0.025). These results suggest that there is a decrease in the capacity of parietal cells to secrete acid following vagotomy. In addition, the decrease in cAMP utilization following vagotomy suggests that the cAMP second messenger system is dependent, at least in part, on an intact vagus nerve.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1989

Prostaglandin E analogue inhibition of pancreatic enzyme secretion.

The effect of native prostaglandins and their methylated analogues on pancreatic enzyme secretion remains unclear, with previous studies reporting inconsistent results. To determine whether the E series prostaglandins directly influence pancreatic secretion, we studied the effect of rioprostil, a prostaglandin E1 analogue, and 16,16-dimethyl prostaglandin E2 (DMPGE2), a prostaglandin E2 analogue, on enzyme release from dispersed guinea pig pancreatic acini. Basal amylase release (4.3 +/- 0.6% of total acinar content) was not altered by either analogue (10(-10)-10(-5) M). A 50% inhibition of maximal cholecystokinin stimulation (10(-9) M; 28.8 +/- 1.2%) was seen with rioprostil (10(-7) M; 14.6 +/- 1.3%) and DMPGE2 (10(-6) M; 15.9 +/- 0.7%) (both p less than 0.005). Prostaglandin inhibition of carbachol-stimulated amylase was less pronounced. The most effective inhibitory dosage with maximal carbachol (10(-5) M; 30.2 +/- 1.9%) was 10(-6) M for both rioprostil (19.2 +/- 1.6%) and DMPGE2 (22.4 +/- 1.7%) (both p less than 0.005). Incubation of acini with A23187, phorbol ester, and 1-oleoyl-2-acetyl-glycerol resulted in a dose-dependent increase in amylase release that was not altered by maximal concentrations of either prostaglandin analogue. Our results indicate that rioprostil and DMPGE2 can directly inhibit pancreatic acinar secretion. This effect appears to occur before activation of the inositol phospholipid system.

16,16-Dimethylprostaglandin E2↗

PubMed1989

Effects of the CCK receptor antagonist L364,718 on pancreatic growth in adult and developing animals.

Although exogenous administration of cholecystokinin (CCK) or dietary manipulation to increase circulating CCK have previously been shown to promote pancreatic growth, the role of CCK in controlling normal pancreatic development remains unclear. A potent CCK receptor antagonist, L364,718, was administered to rats, guinea pigs, and hamsters to block the effect of endogenous CCK. Animals were given continuous infusions of L364,718 (25 nmol.kg-1.h-1), CCK octapeptide [(CCK-8) 200 pmol.kg-1.h-1], or both CCK-8 and L364,718 for 14 and 28 days. Adult (4-mo-old) and young (4-wk-old) animals were used. CCK-8 and L364,718 were administered via separate, subcutaneously implanted mini-osmotic pumps. Infusions of CCK-8 alone for 28 days resulted in a 21.7% increase in wet pancreatic weight in 4-wk-old rats and a 22.7% increase in 4-wk-old guinea pigs (both P less than 0.001 compared with controls). Similar increases were found in DNA, RNA, and total protein contents. Coadministration of L364,718 totally blocked the trophic effects of exogenously infused CCK-8 in rats and guinea pigs. Administration of L364,718 alone in hamsters, guinea pigs, and rats for 14 and 28 days failed to alter the normal growth of the pancreas gland as measured by these parameters. Although elevated levels of CCK appear to promote a potent trophic response in the growing pancreas, this regulatory peptide does not appear to be an essential trophic factor for the normal growth of the exocrine pancreas in these animals.

Aging↗

PubMed1989

Deoxycholate-stimulated release of peptide YY from the isolated perfused rabbit left colon.

The purpose of this study was 1) to measure the effect of graded concentrations of oleic acid and deoxycholic acid (DCA) on the release of peptide YY (PYY) and enteroglucagon and 2) to test whether DCA-stimulated release of PYY was neurally mediated by blocking neuronal conduction with tetrodotoxin. Studies were performed in isolated left colons from New Zealand White rabbits. Oleic acid in concentrations from 0.22 to 22 mM suspended in 10 mM DCA significantly stimulated release of PYY (P less than 0.01) but resulted in no graded response (Bartlett's test, P = 0.15). Similarly, oleic acid (2.2 mM) suspended with ursodeoxycholic acid (10 mM) produced no increased release of PYY above that achieved by ursodeoxycholic acid alone. In contrast, oleic acid (2.2 and 22 mM suspended with 10 mM DCA) produced a graded release of enteroglucagon during the stimulated period. Deoxycholic acid caused a concentration-dependent release of PYY (1, 3.3, 10, and 25 mM) during the stimulated period. Deoxycholic acid (1 and 10 mM) did not significantly increase enteroglucagon release. Tetrodotoxin blockade had no effect on release of PYY stimulated by 10 mM DCA. Because PYY and enteroglucagon are both found in colonic endocrine cells, these results suggest that the release of PYY and enteroglucagon are mediated by specific secretagogues and not simply caused by noxious effects of the agonists. Also, this study has demonstrated that DCA-stimulated release of PYY is not dependent on neuronally mediated mechanisms.

Animals↗

PubMed1989

Gut hormone release by intraduodenal stimulation in duodenal ulcer patients.

After an overnight fast, plasma levels of gut peptide hormones were determined before and after intraduodenal stimulation (IDS) with glucose and citric acid in 8 patients with a recent endoscopically proved duodenal ulcer (DU) attack and in 8 healthy volunteers. The DU patients had a hyperacidic mean BAO of 6.6 and an average PAO of 41.8 mEq/h. In DU, basal secretin levels were similar to those in controls, and after IDS secretin release was not impaired. There was no defect of VIP liberation or of the neurotensin response (basal 21 +/- 7 vs 16 +/- 3, after IDS 68 +/- 28 vs 35 +/- 5 pmol/l) which could account for gastric acid hypersecretion. Although fasting GIP levels were significantly lower than in controls (16 +/- 2.5 vs 25 +/- 1.4 pmol/l), they did not correlate negatively with BAO. In contrast to former studies with oral test meals, integrated GIP release was rather reduced after IDS. Basal plasma levels of gastrin were significantly lower in DU (4.0 +/- 0.4 vs 12 +/- 2 pmol/l) and were inversely related to BAO (r = -0.82, p less than 0.02). From the present data, there is insufficient evidence for abnormal plasma levels of gut hormones as major etiologic factors for basal hyperchlorhydria in ordinary DU disease.

Adult↗

PubMed1989

Coeliac sprue: abnormalities of the hormone profile of gastroduodenal mucosa.

To further characterize coeliac sprue, the hormonal content of routine endoscopic biopsies of gastroduodenal mucosa was estimated in 5 coeliac sprue patients and in 8 volunteers without upper gastrointestinal disease. Levels of cholecystokinin-like immunoreactivity tended to be lower in duodenal mucosa of coeliac sprue patients, while the mucosal map of GIP and somatostatin exhibited no peculiar profile. Gastrin was markedly elevated in the antral mucosa of coeliac sprue patients (3013 +/- 760 versus 1048 +/- 392 pmol/g), while basal plasma gastrin was normal. The mucosal VIP content of the descending duodenum was significantly higher in coeliacs than in controls (409 +/- 161 versus 81 +/- 16 pmol/g) and tended to be increased also in the remaining upper small intestine. This rise may be a reaction to mucosal irritation and a reason for enhanced fluid secretion. Even in antral mucosa of coeliac sprue patients, VIP levels were elevated when compared to controls (82 +/- 14 versus 40 +/- 8 pmol/g) and may have some impact, e.g. on local mucosal blood flow or mucus secretion. The mucosal concentration of another putative neurotransmitter, substance P, also showed a tendency to be raised in the mucosa of upper small intestine of coeliac sprue patients.

Biopsy↗

PubMed1989

Hypergastrinemia after vagotomy is not associated with decreased gastric somatostatin.

Although hypergastrinemia occurs after vagotomy, the mechanisms responsible are not understood. Somatostatin (SRIF) is a peptide that inhibits gastrin release, is present within the gastric fundus and antrum, and is under vagal control. In this study we have investigated the hypothesis that hypergastrinemia is associated with a decrease in gastric SRIF. We examined tissue levels of SRIF in gastric mucosa and muscle wall in rabbits undergoing vagotomy and pyloroplasty compared with sham-operated controls. We also compared the release of SRIF from gastric glands in response to vasoactive intestinal peptide and calcitonin gene-related peptide. Vagotomy resulted in an increase in gastrin compared with controls in both antrum (1062 +/- 176 pmol/gm vs 484 +/- 48 pmol/gm) and plasma (236 +/- 72 pmol/L vs 29 +/- 4 pmol/L; p less than 0.05). This was accompanied by an increase in the number of gastrin cells (25 +/- 4 vs 9 +/- 3; p less than 0.05). No significant differences were observed in gastric SRIF levels in either the fundus or antrum (p greater than 0.5). In addition, there were no differences in the release of SRIF from gastric glands of vagotomized animals compared with controls in response to vasoactive intestinal peptide and calcitonin gene-related peptide (p greater than 0.5). These data suggest that the elevations in plasma and antral gastrin levels after vagotomy are not a result of alterations in gastric SRIF.

Animals↗

PubMed1989

H2-receptor blockade induces peptide YY and enteroglucagon-secreting gastric carcinoids in mastomys.

Gastric carcinoid tumor formation has been reported with prolonged achlorhydria in both animals and human beings. The hypothesis in this study was that the ablation of parietal cell function in an animal (mastomys) genetically predisposed to gastric neuroendocrine neoplasia would promote and accelerate tumor formation. Loxtidine, an irreversible H2-receptor blocker, was administered at 1 mg/kg/day in drinking water for 4 months to young mastomys (n = 16). After 4 months of treatment, 14 of 16 animals had gastric carcinoids compared with 0 of 16 young control animals and 4 of 16 older control animals. Ultrastructurally, these tumors were characterized by the presence of neurosecretory granules. Serum gastrin levels were elevated (230 +/- 40 pmol/L) in loxtidine-treated animals compared with control animals (26 +/- 8 pmol/L) (p less than 0.05). In addition, both peptide YY (620 +/- 160 pmol/L) and enteroglucagon (500 +/- 147 pmol/L) were significantly elevated compared with control groups (p less than 0.05). Similarly, in tumor tissue, peptide YY (676 +/- 152 pmol/gm) and enteroglucagon (551 +/- 164 pmol/gm) were found in large quantities, whereas gastrin was undetectable. These observations provide substantial support for the possible pathophysiologic role of gut peptides, particularly gastrin, in the generation of endocrine neoplasia. The advent of endocrine tumors after inhibition of a gut secretory cell (parietal) may be of considerable significance in understanding the genesis of endocrine neoplasia. Whether the drug acts as a neoplastic promoter of enterochromaffin-like cells or the tumor development is related to elevation of peptides such as gastrin cannot be established in this study. Long-term H2-receptor blockade with new potent, irreversible agents as an alternative to surgery may have potential grave implications that require careful consideration.

Animals↗

PubMed1989

Malignant diathesis from jejunal-ileal carcinoids.

A facet of carcinoid tumors often not recognized is their close association with other, noncarcinoid malignancies. The clinical course of two patients with multiple ileal-jejunal carcinoids and multiple other noncarcinoid malignancies is described. These patients were found to have elevated circulating levels of gastrin, bombesin, glucagon, enteroglucagon, pancreatic polypeptide, and peptide tyrosine tyrosine. These regulatory peptides have been demonstrated to promote trophic effects on the gastrointestinal tract as well as malignant tumors. We propose that the release of these bioactive hormones into the portal and systemic circulation by carcinoid tumors may play some role in their association with these multiple second tumors.

Adolescent↗