Biomedical subjects

J C Thompson

Publications and source records attributed to J C Thompson.

At least 199 records · Page 11Linked to original sources

PubMed1990

Effect of oral fat on plasma levels of neurotensin and neurotensin fragments in humans. Characterization by high-pressure liquid chromatography.

The effect of ingestion of fat (Lipomul 1 g/kg) on the circulating levels of neurotensin (NT1-13) and amino-terminal fragments (NT1-8, NT1-11) and carboxy-terminal fragment (NT8-13) of NT were investigated in six healthy male volunteers. NT and NT fragments were extracted from plasma collected at 0, 15, 30, and 60 min after ingestion of fat, and the plasma levels of NT1-13 and NT fragments were characterized using high-pressure liquid chromatography and radioimmunoassay techniques. Significant elevations of plasma levels of NT1-8, NT1-11, and NT1-13 were observed at 15, 30, and 60 min after fat ingestion. The maximum elevations were 273% for NT1-8, 234% for NT1-11, and 54% for NT1-13. NT8-13 levels failed to rise significantly when compared to basal levels. These findings indicate that both the amino-terminal and carboxy-terminal fragments of NT are either released along with intact NT or are formed as metabolites from NT1-13 in response to ingestion of fat in man.

Administration, Oral↗

PubMed1990

Terbutaline, a beta 2-adrenoreceptor agonist, inhibits gastric acid secretion and stimulates release of peptide YY and gastric inhibitory polypeptide in dogs.

Terbutaline, a beta 2-adrenoreceptor agonist, inhibits pentagastrin-stimulated gastric acid secretion. The purpose of this study was to examine the effect of intravenous administration of terbutaline on plasma levels of peptide YY (PYY) and gastric inhibitory polypeptide (GIP), both of which are known to inhibit gastric acid secretion. Seven dogs with gastric and duodenal fistulas were given pentagastrin (1 microgram/kg/hr) intravenously for 150 min in combination with terbutaline (10 or 20 micrograms/kg/hr) or saline during the 60- to 120-min period of pentagastrin infusion. Pentagastrin-stimulated gastric acid secretion was significantly (P less than 0.05) inhibited by intravenous administration of terbutaline. Terbutaline significantly increased plasma PYY levels, 24% in response to terbutaline at 10 micrograms/kg/hr, and 59% at 20 micrograms/kg/hr. Plasma GIP levels were also increased significantly, 24% with terbutaline at 10 micrograms/kg/hr, and 39% at 20 micrograms/kg/hr. Our data suggest that terbutaline-induced inhibition of pentagastrin-stimulated gastric acid secretion is mediated, at least in part, by the release of PYY and GIP. The adrenergic nervous system may influence gastric acid secretion through the release of PYY and GIP.

Animals↗

PubMed1990

Growth-promoting effects of gastrin on mouse colon cancer cells in vitro: absence of autocrine effects.

We have previously demonstrated trophic effects of gastrin on mouse colon cancer (MC-26) cells, in vivo, and demonstrated the presence of gastrin receptors (GR) on these cells. The cellular and intracellular mechanism by which gastrin expresses trophic effects on colon cancer cells is, however, as yet unknown. For us to start investigating the possible mechanisms involved, it was important that we first develop an in vitro model, in which gastrin expresses its trophic effects directly on the MC-26 cells. The growth-promoting effects of gastrin on the MC-26 cells were examined in various in vitro culture models, in terms of [3H]thymidine incorporation and cell number. A significant trophic effect of gastrin could be demonstrated on quiescent cells in culture, in the absence of serum. The optimal cell-culture conditions for observing trophic effects of gastrin were defined and included a 24-h period of rapid growth of MC-26 cells in serum-supplemented normal growth medium, followed by a 24-h period of culture in serum-free medium containing an optimal dose (1.0 mM) of thymidine, to achieve growth-arrest of the cells. Addition of gastrin (0.5 to 25 nM) to the quiescent, growth-arrested cells resulted in significant dose-dependent increases in both the incorporation of [3H]thymidine uptake by the cells, and a significant increase in cell number. The concentration of GR on the growth-arrested quiescent MC-26 cells in culture was significantly increased compared to the GR concentration on the control, asynchronized cells. The increased presence of GR on the growth-arrested, synchronized MC-26 cells may have allowed us to observe a significant trophic effect of gastrin on the MC-26 cells, in vitro itself. To determine if gastrin was functioning as an autocrine growth factor for MC-26 cells, we examined the effect of gastrin antibodies on the growth of MC-26 cells; no significant effect of the antigastrin IgG on the growth of MC-26 cells was observed.

Animals↗

PubMed1990

Effect of age and sensitivity to cholecystokinin on gallstone formation in the guinea pig.

The purpose of this study was to evaluate the effect of age and the role of cholecystokinin therapy on gallstone formation in guinea pigs. Guinea pigs (31 1-mo-old, 31 1-yr-old, and 23 3-yr-old) were placed on a cholelithogenic diet for 2 wk while another 10 guinea pigs of each age group remained on regular chow. Half of each group received a daily injection of cholecystokinin (0.5 nmol/kg). After 2 wk, guinea pigs were killed and the gallbladders were examined for gallstones. The concentrations of bile constituents were determined. The prevalence of gallstones was: 1-mo-old, control 0 out of 16, cholecystokinin 1 out of 15; 1-yr-old, control 3 out of 14, cholecystokinin 5 out of 16; 3-yr-old, control 10 out of 11, cholecystokinin 3 out of 8. Gallstone formation was significantly greater in 3-yr-old controls than in the two younger control groups, and cholecystokinin treatment significantly reduced the incidence of gallstones to near the level seen in younger guinea pigs. In the two younger age groups (but not in the 3-yr-old group), the cholelithogenic diet significantly reduced the concentration of bile salts in bile below that of guinea pigs on a normal diet. The cholelithogenic diet and treatment with cholecystokinin did not alter the relative compositions of bile lipids from that of guinea pigs on a normal diet in any of the three ages studied. In the second experiment we measured gallbladder emptying in response to exogenous infusion of cholecystokinin-8 (100 fmol/kg/h-100 nmol/kg/h) in the same three age groups of guinea pigs in vivo that had been maintained on regular chow. There was no difference in cholecystokinin sensitivity between the two younger age groups, but both were significantly more sensitive to cholecystokinin than the 3-yr-old guinea pigs in rate of gallbladder emptying in the dose range 1 pmol/kg/h-1 nmol/kg/h. We conclude that a major factor in the increased incidence of gallstone formation in the aged guinea pig gallstone model is decreased gallbladder emptying due to decreased gallbladder sensitivity to cholecystokinin.

Aging↗

PubMed1990

Role of gastrin in bombesin-stimulated somatostatin release.

The intermediary pathways in the bombesin-induced somatostatin release were examined in isolated perfused rat stomach obtained from male rats that were fasted overnight. The stomachs were perfused by way of the celiac artery. On coinfusion of 1.0 mumol/L tetrodotoxin and 1 nmol/L bombesin, a significant depression in release of somatostatin was observed compared with that observed with bombesin alone. The 5-minute integrated somatostatin response after treatment with tetrodotoxin and bombesin was 173% +/- 14% of basal, which was significantly lower than that observed with bombesin alone (394% +/- 59% of basal, P less than 0.05) but significantly higher than that observed with medium-199 alone (95% +/- 7% of basal, P less than 0.05); this indicated that approximately 70% of the bombesin-stimulated somatostatin release was indirectly mediated through neural pathways, while a significant (approximately 30%) segment of it was mediated by nonneural mechanisms. To test if the 30% somatostatin release was secondary to gastrin release in response to bombesin, gastrin antiserum and bombesin (1 nmol/L) were coadministrated in the presence or absence of tetrodotoxin (1 mumol/L). Gastrin antiserum alone did not significantly affect basal release of somatostatin but caused a significant inhibition (approximately 23%) of bombesin-provoked somatostatin release. Coadministration of gastrin antiserum and tetrodotoxin attenuated bombesin-stimulated somatostatin release. Gastrin (1 mumol/L) alone significantly stimulated somatostatin release (150% +/- 10% of basal), which was completely attenuated in the presence of gastrin antiserum. Tetrodotoxin did not affect bombesin-elicited gastrin release, confirming that bombesin-stimulated gastrin release was directly mediated. To determine the nature of the neural pathways mediating the bombesin-induced somatostatin release, atropine (100 nmol/L) was used. Atropine inhibited bombesin-induced somatostatin release to the same extent as tetrodotoxin, indicating that cholinergic pathways mediated bombesin-induced somatostatin release. These results show that almost all the somatostatin response to bombesin is indirectly mediated, and is composed of a major neural (cholinergic) and a minor nonneural pathway. The nonneural mechanism appears to be contributed primarily by gastrin released in response to bombesin, which apparently has a short paracrine positive feedback effect on somatostatin release.

Animals↗

PubMed1990

Stimulatory effect of pancreastatin on gastric acid secretion in conscious dogs.

Pancreastatin, a new 49-amino acid peptide, has recently been isolated and characterized from extracts of the porcine pancreas. The objective of the present study was to examine the effect of various doses of pancreastatin on gastric acid secretion in conscious dogs that were prepared with chronic gastric cannulas. Pancreastatin, administered IV at 400 pmol.kg-1 x h-1, enhanced peptone meal [peptone (5%), phenylalanine (90 mmol/L), glucose (12 g/dL)]-stimulated gastric acid secretion by 50%; pancreastatin at 800 pmol.kg-1 x h-1 enhanced peptone meal secretion by 165% (P less than 0.05). Intravenous administration of pancreastatin did not affect basal or peptone-stimulated release of gastrin. In addition, IV pancreastatin (400 pmol.kg-1 x h-1) failed to influence basal gastric acid secretion. Pancreastatin did not affect acid secretion stimulated by 2-deoxyglucose, histamine, or pentagastrin. The present study shows that pancreastatin can selectively enhance gastric acid secretion by a mechanism independent of cholinergic, histaminergic, or gastrin input.

Animals↗

PubMed1990

The pathology of an inherited hyperlipoproteinaemia of cats.

The gross and histological features of congenital lipoprotein lipase deficiency are described in eight cats. The main histological features could be directly related to the presence of the chylomicronaemia. They consisted of lipid accumulation within clear vacuoles or ceroid accumulation within residual bodies in parenchymatous organs such as the liver, spleen, lymph nodes, kidney and adrenal gland. Xanthomata were seen in various sites, probably arising either from frank haemorrhage or the leakage of lipid-rich plasma perivascularly. As in human lipoprotein lipase deficiency there was no evidence of the formation of atherosclerotic plaques. Focal degenerative changes were, however, present within arteries and this may indicate blood vessel weakness and explain the tendency to haemorrhage and xanthomata/granulomata formation. The degeneration and fibrous replacement of glomeruli and nephrons possibly arises from pressure necrosis of adjacent xanthomata and alterations in renal blood flow.

Animals↗

PubMed1990

The effect of age on small bowel adaptation and growth after proximal enterectomy.

We examined the effect of age on the adaptive capacity of small bowel mucosa following 60% enterectomy. Two groups of male Fischer 344 rats (3 mo old and 26 mo) underwent either a mid-small bowel transection and reanastomosis (control) or 60% proximal enterectomy beginning at the duodenojejunal junction. Rats were sacrificed at 5, 14, and 21 days after operation, and the mucosa was weighed and assayed for DNA, RNA, protein, and polyamine concentration and content. Ornithine decarboxylase activity was also measured in ileal mucosa at 5 days after surgery. Young rats had completed the adaptive hyperplastic response within 2 weeks after operation by all biochemical measurements; similar adaptation was not seen until 3 weeks after operation in the old rats. We conclude that although the capacity to achieve intestinal adaptation after enterectomy is preserved into old age in rats, this compensatory response is delayed.

Adaptation, Physiological↗

PubMed1990

Effects of aging on duodenal bicarbonate secretion.

The incidence of duodenal ulcer increases with age, but acid secretion does not. We have investigated the effects of aging on a mechanism of duodenal mucosal defense. Basal and acid-stimulated bicarbonate secretions were measured in the proximal duodenum in anesthetized rats of three different age groups (3 months, 1 year, and 2 years). The proximal duodenum was cannulated in situ between two plastic tubes that extend downward from a titrating chamber, and bicarbonate secretion was measured by the method of Flemström et al. Although there was no significant difference in basal secretion among three groups, bicarbonate secretion in response to luminal acid (100 mmol/L [millimolar] HCl) was diminished in 1-year-old and 2-year-old rats (1-hour integrated bicarbonate secretions; 3 months = 5.8 +/- 0.7; 1 year = 3.1 +/- 1.0*; 2 years = 2.0 +/- 0.7*). We also studied the effects of two mediators for acid-stimulated duodenal bicarbonate secretion, vasoactive intestinal polypeptide (VIP), and prostaglandin E2 (PGE2). Intravenous infusion of VIP (0.4, 4, 40 nmol/kg/hr) and intraluminal administration of PGE2 (10(-5) mol/L [molar] and 10(-4) mol/L) induced duodenal bicarbonate secretion in a dose-dependent manner in all three groups, without significant difference between groups. These findings suggest that the release of mediator(s) in response to acid is decreased in the duodenum of the aging rats. The progressive breakdown in mucosal defense mechanisms with increasing age may explain, at least in part, the age-related increase of incidence of duodenal ulcer disease.

Acid-Base Equilibrium↗

PubMed1990

Effect of somatostatin and tamoxifen on the growth of human pancreatic cancers in nude mice.

We studied the effects of SMS 201-995 (SMS), a somatostatin analog, and tamoxifen, an antagonist of estrogenic actions, on the growth of human pancreatic cancers (SKI and PGER) in vivo. Male nude mice were inoculated with either SKI or PGER by passage of tumor chunks (3 mm2) to the scapular region. Mice from each tumor group were randomly allocated to one of four treatment groups: group 1, control group; group 2, SMS (100 micrograms/kg t.i.d.); group 3, tamoxifen (10 mg/kg three times a week); and group 4, SMS (100 micrograms/kg t.i.d.) + tamoxifen (10 mg/kg three times a week). The somatostatin analog, SMS, given alone or as a combined regimen with tamoxifen, significantly reduced (a) the rate of growth of SKI, and (b) DNA, RNA, and protein content of the tumors. On the other hand, in the case of PGER tumors, none of the treatment regimens significantly influenced the growth of PGER in vivo. Despite showing no significant effects during the study, PGER tumors in mice receiving tamoxifen alone had significantly lower total DNA, RNA, and protein contents compared to control tumors; this was reversed on combined treatment with SMS. None of the growth parameters of PGER was effected by SMS alone. We conclude that, in the case of SKI, SMS with or without tamoxifen was effective as a growth inhibitory agent, whereas in the case of PGER, tamoxifen alone was effective. This finding suggests that independent pathways mediate the growth-inhibitory effects of tamoxifen and SMS, and that different pancreatic cancers may respond to the two agents differently, some with inhibition, some not.

Animals↗

PubMed1990

Intestinal phase of pancreatic polypeptide release: the effect of segmental perfusion of the small intestine with various secretagogues.

The purpose of this study was to examine the effect of various nutrients perfused selectively into isolated sections of the small intestine on the release of pancreatic polypeptide (PP). Six dogs were prepared with chronic gastric, duodenal, and three permanent intestinal fistulas (one distal to the ligament of Treitz, one in the terminal ileum, and one halfway between). After a 24-h fast, the duodenum was perfused for 45 min (200 ml/h) via the duodenal limb with HCl (30 mM), an amino acid solution (50 mM), or sodium oleate (NaO, 40 mM). In separate studies, the jejunal and ileal segments were isolated by inflating two balloon catheters via the intestinal fistula, and these segments were perfused as described earlier. Plasma PP, cholecystokinin (CCK)-33, and secretin levels were measured. Results of this study showed that the perfusion of all segments of the small intestine with amino acid caused a significant elevation of plasma PP levels. Perfusion of the duodenum and jejunum but not the ileum with a fatty acid resulted in a significant elevation of plasma levels of PP. Perfusion of HCl into any segment did not affect plasma levels of PP. This study shows that PP is released by the presence of nutrients in all segments of the small intestine, and that a PP elevation was always accompanied with a rise in plasma levels of CCK-33.

Animals↗

PubMed1990

Autoanti-Ge associated with severe autoimmune hemolytic anemia.

Severe autoimmune hemolytic anemia due to anti-Ge is described. The patient's red cells had a positive direct antiglobulin test, and they typed as Ge+ using saline reactive reagents. Anti-Ge was eluted from her RBCs, and her serum had an IgG and IgM anti-Ge2,3.

Adult↗

PubMed1990

Reduced cholecystokinin mediates the inhibition of pancreatic growth induced by bile salts.

The effects of luminal bile salts on plasma levels of cholecystokinin (CCK) and growth of the pancreas in mice were studied. Nonfasting levels of plasma CCK in control mice were 8.1 +/- 1.5 pM. Feeding mice a 0.5% (wt/wt) sodium taurocholate-supplemented diet for 1 wk significantly lowered nonfasting levels of plasma CCK to 4.1 +/- 0.5 pM and decreased the total contents of pancreatic DNA by 22%, RNA by 25%, and protein by 24%. All of the inhibitory effects of taurocholate on pancreatic growth were completely reversed by the simultaneous administration of CCK-8 (3 micrograms/kg, 3 times daily). In contrast, intraluminal neutralization of endogenous bile salts by feeding a 4% (wt/wt) cholestyramine-supplemented diet for 1 wk significantly elevated nonfasting levels of plasma CCK to 14.7 +/- 1.5 pM and increased the total contents of pancreatic DNA by 34%, RNA by 40%, and protein by 35%. All of the stimulatory actions of cholestyramine on pancreatic growth were completely abolished by the administration of the highly potent and specific CCK-receptor antagonist L364,718 (1 mg/kg, twice daily). These findings, therefore, indicate that bile salts appear to play a physiological role in pancreatic growth by regulation of plasma levels of CCK.

Animals↗

PubMed1990

Intravenous amino acids stimulate human gallbladder emptying and hormone release.

Gallbladder stasis during prolonged total parenteral nutrition (TPN) has been documented. We have examined the effect of intravenous amino acid infusion on human gallbladder contraction and release of cholecystokinin (CCK). Five healthy adult volunteers were given amino acid infusions at different rates (65, 125, 240, and 600 mg.kg-1.h-1). The volume of the gallbladder was calculated by means of ultrasonographic measurements. Plasma samples were analyzed for CCK immunoreactivity. Gallbladder and hormone responses after intravenous amino acids were compared with responses after a fat meal, after a protein meal, and after ingestion of an oral amino acid mixture. We found that intravenous amino acids stimulated human gallbladder contraction in a dose-related manner. The mechanism of stimulation may be through the release of CCK although significant correlation was not demonstrated. The magnitude of response is similar to that seen after meal stimulation. To compare the delivery of amino acids during a standard meal and during each dose of intravenous amino acids, peripheral plasma levels of dietary amino acids were measured after a standard commercially prepared enteral supplement meal and after each dose of intravenous amino acids. Our lower doses of amino acid infused resulted in levels of circulating amino acid comparable to those after a meal. The induction of gallbladder contraction and release of CCK in human recipients of parenteral nutrition may be of value in some circumstances.

Adult↗

PubMed1990

Protective action of luminal bile salts in necrotizing acute pancreatitis in mice.

Bile salts in the intestinal lumen act to inhibit the release of cholecystokinin (CCK). Recent studies have shown that CCK may play a permissive role in the development of acute pancreatitis. In this study, the amount of luminal bile salts in female Swiss Webster mice was either decreased by feeding 4% (wt/wt) cholestyramine or increased by feeding 0.5% sodium taurocholate for 1 wk. Plasma levels of CCK were stimulated by cholestyramine and inhibited by taurocholate. Then, acute pancreatitis was induced either by caerulein injections, or by feeding a choline-deficient, ethionine-supplemented (CDE) diet. Feeding of cholestyramine significantly decreased survival from 25% to 0% in the CDE pancreatitis, and increased the magnitude of elevation of serum amylase levels and the extent of pancreatic necrosis in both models of pancreatitis; CCK-receptor blockade with CR-1409 completely abolished the adverse effects of cholestyramine. In contrast, feeding of taurocholate significantly increased survival to 100% and decreased the elevation of serum amylase and pancreatic necrosis; CCK-8 antagonized these actions of taurocholate. Luminal bile salts appear to provide a physiologic protection against necrotizing pancreatitis, at least in part, both by inhibiting the release of CCK and by promoting resistance of the pancreas to CCK excessive stimulation in vivo.

Acute Disease↗

PubMed1990

The effect of somatostatin on 5-hydroxytryptamine release from a carcinoid tumor.

One of the major manifestations of the carcinoid syndrome is secretory diarrhea thought to be due to overproduction of 5-hydroxytryptamine (5-HT). Synthetic somatostatin analogues have proved to be clinically effective in controlling this diarrhea. We have established a continuous cell line from a human pancreatic carcinoid tumor that secretes 5-HT. We examined the ability of the somatostatin analogue, SMS 201-995, to inhibit 5-HT release in vitro. Tumor cells were exposed to SMS 201-995 (10(-6) mol/L), pentagastrin (10(-9) mol/L), acetylcholine (10(-5) mol/L), and isoproterenol (10(-5) mol/L) alone and in combination; 5-HT release was assayed with high pressure liquid chromatography. We found that pentagastrin (6.43 +/- 0.64 ng/ml), isoproterenol (20.24 +/- 2.17 ng/ml), and acetylcholine (12.39 +/- 1.10 ng/ml) each stimulated release of 5-HT compared to control values (4.38 +/- 0.42 ng/ml). SMS 201-995 significantly reduced release of 5-HT in response to isoproterenol and acetylcholine but did not inhibit the effect of pentagastin. These data suggest that different agents do not act through the same pathway to stimulate 5-HT release from human pancreatic carcinoid cells.

Acetylcholine↗

PubMed1990

In vivo comparison of inhibition with proglumide and CR-1409 of cholecystokinin-induced pressure in the biliary tract of the guinea pig.

This study was done to compare the effects of two cholecystokinin antagonists, proglumide and CR-1409, on cholecystokinin-induced changes in intrabiliary pressure in vivo. We have substantially modified the constant infusion biliary manometry model, successfully used in large animals, to measure contractility of the gallbladder in guinea pigs. A silicone catheter for manometry was placed in the fundus of the gallbladder of an anesthetized guinea pig, and the biliary tree was constantly infused at 0.1 milliliter per minute with normal saline solution. The intraluminal pressure of the system was continuously recorded. The model was used to demonstrate a dose-response curve to bolus administration of exogenous cholecystokinin (0.01 to 1.0 nanomole per kilogram) and also to study the actions of proglumide, an antagonist to gastrin and cholecystokinin, and CR-1409, a newer, specific cholecystokinin antagonist, on cholecystokinin-induced contraction of the gallbladder of the guinea pig in vivo. Proglumide, at a dose of 5 millimoles per kilogram, completely abolished increases in intrabiliary pressure caused by cholecystokinin (0.5 nanomole per kilogram), whereas this effect was achieved by only 5 micromoles per kilogram of CR-1409. In both, there was full recovery from cholecystokinin antagonism within one hour. CR-1409 is one thousand times more potent than proglumide against cholecystokinin-induced changes in intrabiliary pressure in vivo and appears to be a useful pharmacologic reagent to study cholecystokinin-mediated components of physiologic contraction of the gallbladder.

Animals↗

PubMed1990

Additive interactions of calcitonin gene-related peptide and calcitonin on pancreatic exocrine function in conscious dogs.

By convention, establishing a physiologic role for a gut peptide requires demonstration of biologic activity that can be reproduced by exogenous administration of the peptide in amounts that yield plasma concentrations that are not higher than those found after a meal. We have tested the hypothesis that the combined action of two inhibitory peptides may lower the effective doses of each. We further hypothesize that combined peptide responses may be responsible for the action of peptide hormones that have been difficult to demonstrate as physiologically relevant mediators, when examined as independently acting substances. In conscious dogs prepared with chronic pancreatic cannulas, stimulated pancreatic exocrine secretions were depressed in a dose-related manner by intravenous infusions of calcitonin (CT) and calcitonin gene-related peptide (CGRP). Doses of 2.0 nmol/kg/hr of both CT and CGRP yielded maximal inhibition of stimulated secretions of both bicarbonate (greater than 85% inhibition) and protein (greater than 55% inhibition). The lowest effective dose for either CT or CGRP, given alone, was 0.75 nmol/kg/hr, but when infused simultaneously, each at the subthreshold dose of 0.50 nmol/kg/hr, significant inhibition of protein and bicarbonate secretion was achieved. Combined infusions of the submaximal dose of 0.75 nmol/kg/hr resulted in an enhanced inhibitory response. To prove that this effect is not simply combined activation of a common receptor, we tested peptide YY (0.1 to 0.5 nmol/kg/hr) combined with CGRP and obtained similar results. Because a meal simultaneously releases a large number of active peptides, we speculate that such potentiated responses do occur physiologically. Cooperative interaction with other agents may be the primary mode of action for certain gut peptides.

Animals↗