Regulatory peptides in the mammalian respiratory tract.
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Animals↗
Biomedical subjects
T E Adrian
Publications and source records attributed to T E Adrian.
Bombesin: action on gut hormones and calcium in man.
Bombesin, a peptide with widespread biological actions, has been demonstrated in human tissues by immunological methods. To investigate its effect in man, synthetic bombesin was infused at low doses in six male volunteers. Bombesin at 2.4 pmol kg-1 min-1 produced significant rises in plasma insulin, glucagon, pancreatic polypeptide, gastrin, cholecystokinin, motilin, glucose-dependent insulinotropic polypeptide, neurotensin, enteroglucagon, vasoactive intestinal polypeptide, and serum calcium. In contrast, bombesin caused a profound fall in parathyroid hormone levels and reduced plasma glucose concentrations. A late rise in plasma calcitonin was also observed. Bombesin had no significant effect on the pituitary hormones, TSH, GH, PRL, or cortisol. No hormonal changes or alterations in calcium were noted during saline infusions. Bombesin has a marked stimulatory effect on gastrointestinal hormones, which is unique and opposite to the effect of somatostatin, a potent inhibitor of gut hormone release. Bombesin also influences calcium-regulating hormones, either directly or through its action on gut hormones. The bombesin concentrations achieved with the dosages used were low enough to indicate a possible physiological role for the endogenous peptide.
Adult↗
The effects of naloxone and morphine on postprandial gastrointestinal hormone secretion.
Postprandial gastrointestinal hormone secretion was not affected by the intravenous administration of naloxone. However, after the administration of morphine, multiple effects were observed. Postprandial pancreatic polypeptide, motilin, and enteroglucagon secretion were abolished and there was a reduction in the secretion of insulin, gastric inhibitory polypeptide, and neurotensin. There was prolonged secretion of gastrin. Levels of vasoactive intestinal polypeptide, somatostatin, and pancreatic glucagon were not affected. Many of these changes can be accounted for by the ability of morphine to delay gastric emptying. The prolonged secretion of gastrin could result from a combination of impaired gastric emptying and reduced postprandial gastric acid secretion. Inhibition of vagal acetylcholine release is the most likely explanation for the abolition of pancreatic polypeptide secretion. With the exception of the effects on motilin, pancreatic polypeptide, and enteroglucagon secretion this study provides no evidence that opiate substances directly affect the secretion of gastrointestinal hormones.
Adult↗
Effect of neurotensin on pancreatic function in man.
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Adult↗
Effect of gut regulatory peptides of intestinal luminal fluid in the rat.
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Animals↗
Clinicopathological study of pancreatic and ganglioneuroblastoma tumours secreting vasoactive intestinal polypeptide (vipomas).
During a six-year period (1973-9) 52 patients with pancreatic tumours and 10 with ganglioneuroblastomas were found to have raised plasma vasoactive intestinal polypeptide (VIP) concentrations. All the patients had severe secretory diarrhoea, weight loss, dehydration, hypokalaemic acidosis, and a raised plasma urea concentration. Reduced gastric acid secretion was seen in 72% of patients. Plasma VIP concentrations were not raised in patients with diarrhoea due to other types of tumour or disease or in hormone-secreting tumours not associated with diarrhoea. Plasma VIP measurement may therefore give clinical guidance in a patient with persistent watery diarrhoea and hypokalaemic acidosis. Surgical excision was clearly the treatment of choice, but metastatic pancreatic tumours usually responded to streptozotocin.
Adult↗
The effects of caerulein and a meal stimulus on gallbladder intraluminal pressure and bile flow in the pig.
The intraluminal gallbladder pressure has been measured in a conscious unsedated pig model by the use of a radiotelemetry pressure capsule. A loop fistula was incorporated to measure bile output simultaneously. Mean fasting intraluminal gallbladder pressure was found to be 15 +/- 4 mmHg above atmospheric pressure, and mean fasting bile output 7.5 +/- 0.8 ml/10 min. Following intravenous caerulein pressure peaked at 2 min with a mean rise of 17 +/- 3 mmHg above basal (P less than 0.005). Bile output was increased for 30 min following caerulein with a total mean increase for this period of 13.5 +/- 2.2 ml (P less than 0.005). Gallbladder pressure rose significantly 5 min after commencing a meal by 6.0 +/- 1.9 mmHg (P less than 0.025) reaching a peak pressure 65 min after the meal with a mean rise of 14.8 +/- 2.3 mmHg (P less than 0.005). Bile output was significantly increased for 50 min following the ingestion of food. The total increments above basal values for bile output being 15.9 +/- 2.7 ml (P less than 0.005) in the first 30 min post-prandially and 1.6 +/- 2.4 ml (P less than 0.005) in the 30--60 min period. This model re-emphasizes the rapidity of the hormonal response and may be valuable for further studies on the physiology of post-prandial gallbladder emptying.
Animals↗
Effect of a long-acting octapeptide analogue of somatostatin on growth hormone and pancreatic and gastrointestinal hormones in man.
1. The biochemical specificity and duration of action of a single 5 mg subcutaneous dose of des-AA1,2,4,5,12,13-D-Trp8-somatostatin were evaluated in eight patients with symptomatic pancreatic endocrine tumours. 2. There was a reduction by more than 50% for at least 10 h in plasma concentrations of growth hormone, glucagon, gastrin and motilin and for 4--5 h in plasma insulin, pancreatic polypeptide, gastric inhibitory polypeptide and enteroglucagon. 3. This study shows that this octapeptide analogue of somatostatin, like somatostatin itself, lacks specificity in the hormones it suppresses. However, its prolonged duration of action against several hormones when given subcutaneously suggests that it may be of therapeutic use in a number of disease states where excessive plasma concentrations of one or more of these hormones occur.
Gastrointestinal Hormones↗
The mechanism of abnormal pancreatic beta cell response to food following acute hypoglycaemia in man.
Following acute insulin-induced hypoglycaemia, an abnormal pattern of insulin secretion in response to a meal has been demonstrated in six healthy volunteers. This is characterized by an initial impairment in insulin secretion and late hyperinsulinaemia. Postprandial gastrointestinal hormone levels were normal following hypoglycaemia in these subjects. In four other subjects, the administration of intravenous glucose prior to the meal partially reversed the abnormal pattern of secretion. In two patients with a total pre-ganglionic sympathectomy, the pattern of blood glucose, plasma insulin and C-peptide was similar to that observed following hypoglycaemia in normal subjects. It is unlikely that an abnormal entero-insular axis or an elevation of plasma catecholamine levels are primarily responsible for this phenomenon. This effect of hypoglycaemia on postprandial insulin secretion may be caused by glucopenia of the pancreatic beta cells.
Blood Glucose↗
Plasma neurotensin in term and preterm neonates.
The new ileal peptide neurotensin has not been studied hitherto in the human neonate. Plasma concentrations of neurotensin were measured by radioimmunoassay in 276 healthy term or preterm infants either at birth or pre- or post-prandially during the neonatal period. In addition, a group of 10 6-day-old preterm infants were studied who had never been enterally fed on account of hyaline membrane disease. Plasma neurotensin values were obtained also in 12 healthy fasting adults. Term infants had higher plasma neurotensin concentration than preterm infants at birth. Both groups showed a significant postnatal surge in basal (pre-prandial) neurotensin concentrations exceeding adult values, but no postnatal neurotensin elevation was found in the unfed group. In preterm infants, who were studied further into the neonatal period than term infants, there was a progressive increase in the rise of neurotensin following a milk feed, with a massive neurotensin response by 24 days of age. In 6-day-old term infants, the neurotensin response to bottle feeding was significantly greater than to breast feeding. These findings add further weight to the concept that neurotensin may be of physiological importance as a gut hormone. The high neurotensin levels and large feed responses seen in neonates may indicate a unique role for neurotensin in early life.
Bottle Feeding↗
Effect of somatostatin infusion on intermediary metabolism and entero-insular hormone release in infants with hyperinsulinaemic hypoglycaemia.
The hypoglycaemia of infantile hyperinsulinism is often exceedingly difficult to control. The use of somatostatin has been advocated recently in such infants because of its effect on inhibiting insulin release, but nothing is known of the wider effects of this potent hormone in the young child. Two infants presenting at 9 weeks and 5 days of age with severe hyperinsulinaemic hypoglycaemia were studied during an infusion of somatostatin. In both infants normoglycaemia was restored with suppression of insulin secretion. An increase in blood ketone bodies occurred, but no change was seen in blood pyruvate, lactate or alanine concentrations. The plasma concentrations of glucagon, cortisol, growth hormone, motilin, pancreatic polypeptide, gastric inhibitory of polypeptide, neurotensin, gastrin and vasoactive intestinal peptide decreased markedly during the somatostatin infusion. No consistent change occurred in plasma enteroglucagon or secretin values. We conclude that somatostatin effectively suppresses abnormal insulin secretion in infants, but it has profound effects on the release of nine other hormones. Further studies are needed to define the consequences of suppressing the release of these hormones before somatostatin can be used routinely in the management of infantile hyperinsulinism.
Adenoma↗
Effects of vasoactive intestinal peptide and pancreatic polypeptide in rabbit intestine.
The effects of porcine vasoactive intestinal peptide (VIP) and bovine pancreatic polypeptide (PP) on jejunal, ileal, and colonic fluid transport were studied in the rabbit. VIP produced secretion in the small intestine (jejunum greater than ileum) but did not affect absorption in the colon. PP had no secretory effects in jejunum, ileum, or colon. The small intestinal secretion induced by VIP was not associated with raised cAMP concentrations in the mucosa; this suggests that the secretory effects of VIP in vivo are mediated by a mechanism other than stimulation of adenylate cyclase.
Animals↗
Lack of effect of pancreatic polypeptide in the rate of gastric emptying and gut hormone release during breakfast.
Bovine pancreatic polypeptide (PP) was infused intravenously in 5 healthy subjects on two separate occasions with mean doses of 1 and 2 pmol kg-1 min-1, respectively, which achieved plasma levels equal to and twice those observed after a normal mixed breakfast. The gastric emptying rate of a carbohydrate-rich breakfast 20 min after the start of each PP infusion was not significantly different from a control infusion of 0.15 M saline. PP is unlikely to be an important physiological modulator of gastric emptying rate in man.
Adult↗
Pancreatic tumours produce neurotensin.
Tumour tissue may secrete substances which are not normally secreted by the original tissue. We have found that 6 out of 21 pancreatic tumours producing vasoactive intestinal peptide also produce neurotensin-like peptides. These are sometimes secreted and very high plasma levels of neurotensin-like immunoreactivity may be found in the circulation.
Female↗
The effect of somatostatin analogs on secretion of growth, pancreatic, and gastrointestinal hormones in man.
The potency and specificity of somatostatin (SS) and four of its analogs were compared in seven patients with pancreatic endocrine tumors. The analogs tested were [D-Trp8]-SS, [D-Trp8, D-Cys14]-SS, Des-Asn5-[D-Trp8, D-Ser13]-SS, and Des (AA)1,2,4,5,12,13, [D-Trp8]-SS, and they did not show selective effects on the suppression of basal concentrations of GH, insulin, glucagon, pancreatic polypeptide, gastrin, gastric inhibitory peptide, motilin, enteroglucagon, or neurotensin. The observation that the potency of these analogs is similar to that of the parent molecule throws considerable light on the structure/activity relationship of the somatostatin molecule. Des-AA1,2,4,5,12,13, [D-Trp8]-Ss has been reported to have a prolonged action when administered sc. When administered iv, however, this octapeptide analog ws not long acting, suggesting that the prolonged action seen in the previous study was a result of delayed uptake from the injection site. An increment in plasma SS concentrations of 19 +/- 3 pmol/liter suppressed basal concentrations of GH, insulin, glucagon, and several gastrointestinal hormones by more than 50%, suggesting that even small changes in plasma SS levels may be physiologically important.
Adult↗
Physiology of the porcine gastrointestinal regulatory peptides.
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Animals↗
Pancreatic polypeptide from pancreatic endocrine tumours.
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Adenoma, Islet Cell↗
Serum trypsin concentration and pancreatic trypsin secretion in insulin-dependent diabetes mellitus.
Fasting serum trypsin concentration and pancreatic trypsin output, stimulated by secretin and cholecystokinin-pancreozymin, were measured in 18 patients with insulin-dependent diabetes, to assess a possible correlation between these two indices of exocrine pancreatic function. Serum trypsin concentration was subnormal in 13, and pancreatic trypsin output was decreased in 14 patients, but there was no significant correlation between the two measurements. There was no correlation between serum trypsin and residual beta cell function measured by plasma C-peptide immunoreactivity (CPR). After an interval of four years serum trypsin measurements were repeated in 11 subjects. All individual trypsin levels were lower than the previous results, the difference being highly significant (t = 9.0; p < 0.001). Serum trypsin concentration therefore represents a qualitative index of reduced exocrine pancreatic function in diabetes, but has no value in quantitating the degree of deficiency.
Adolescent↗