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[Gastrointestinal hormones during pregnancy--immunoreactive secretin and gastrin in serum and fetal tissue (author's transl)].

The concentrations of immunoreactive secretin (S) and gastrin (G) in maternal peripheral vein (MV) during pregnancy and MV, umbilical artery (UA) and umbilical vein (UV) at delivery and fetal tissue of 19, 23 weeks of gestation obtained after therapeutic abortion were measured by specific radioimmunoassay. S-specific antisera was generated in rabbits against highly purified synthetic S. Newly synthesized S analog (Tyr1)-S was indicated by enzymic method. The radioimmunoassay of S was performed by double antibody method using synthetic S as standard. G was measured by RIA kit (Dainabot radioisotope Lab.). The sensitivity of the assays for S and G was 50 pg/ml. The fetal tissue were extracted by water-boiling method and purified by gel filtration on Sephadex G-25 column. The S levels in MV increase as gestational age advances and reach to the maximum levels of 248 +/- 150 pg/ml, while no increase tendency was noticed in G levels. The S levels in MV, UA and UV at delivery (n = 18) were 307 +/- 158 pg/ml, 460 +/- 166 pg/ml and 424 +/- 126 pg/ml, respectively. The S levels in cord blood is statistically higher than that in MV (p less than 0.05). The G levels in MV, UA and UV were 67 +/- 22 pg/ml, 101 +/- 63 pg/ml and 91 +/- 38 pg/ml. The differences of the values between MV and cord blood are significant (p less than 0.05). S like material in fetal upper gastrointestinal tracts was found high in concentration. The extract of fetal duodenum showed a displacement curve paralleled to that of the standard S. In addition, relatively high concentration of immunoreactive S was found in cerebral cortex obtained from fetus of 23 weeks of gestation. G concentration in fetal tissue was also demonstrated. The evidence of immunoreactive S and G in fetal blood and fetal gastrointestinal tracts was reported. These results may be of importance to provide the information in understanding the physiology of the fetus.

Female↗

Effect of some gastrointestinal hormones on motor and electrical activity of the digestive tract in the conscious cat.

Three peptides structurally related to gastrin and known to be full agonists of antral motility in the conscious cat, pentagastrin (PG), cholecystokinin (CCK) and synthetic octapeptide of cholecystokinin (OP-CCK), were compared in relation to antral and duodenal electrical activity. They induced the same antral effect in eliciting an increase in the basal electrical rhythm (BER) and a short-lasting decrease in the frequency of the bursts of spikes. The electrical changes were correlated with lumen pressure changes measured in parallel, consisting of a decrease in the frequency of high-amplitude peaks and an increase in low-amplitude peaks. The additive effect of PG and CCK shows that the peptides are full agonists for antral electrical activity, as they are for antral motility and acid secretion. In contrast to the antrum, the three peptides increased the frequency of the duodenal spike bursts, CCK and OP-CCK decreased the BER frequency, while PG increased BER slightly. The increase in antral and duodenal BER obtained after a beef-liver meal, which produced a large endogenous gastrin release, suggests a major role for gastrin in antral motility induced by feeding, at least in the cat.

Animals↗

Effect of gastrointestinal hormone infusions of lower oesophageal competence of rhesus monkeys.

The lower oesophageal high pressure zone (HPZ) was studied in 5 non-refluxing and 3 refluxing Rhesus monkeys. The changes in HPZ and reflux status in response to infusion of various doses of secretin, cholecystokinin and glucagon were measured in all animals, and, in the 5 non-refluxing monkeys, after oesophagogastrectomy with replacement of the lower oesophagus by a stomach tube. All three hormones consistently produced a transient decrease in the HPZ pressure. The only change in response following oesophagagastrectomy and gastric tube replacement was a significant delay in the response to each hormone. Neither hormone infusion nor operation altered gastro-oesophageal reflux status. It appears that lower oesophageal competence in primates is more dependent on the presence of narrow, muscular, intra-abdominal tube than on a specialized segment of the lower oesophagus.

Animals↗

Central versus peripheral effects of bombesin on the release of gastrointestinal hormones in dogs.

This study compared the effects of bombesin given intracerebroventricularly and intravenously on circulating levels of gastrin, pancreatic polypeptide (PP), and cholecystokinin (CCK-33). Bilateral cannulas were implanted permanently into the lateral cerebral ventricles of five dogs. An intravenous (IV) bolus injection of bombesin (0.25 microgram/kg) significantly elevated circulating levels of gastrin, PP, and CCK-33. Vagotomy inhibited the release of PP that was induced by IV bombesin, but vagotomy did not affect gastrin and CCK-33 responses. Intracerebroventricular injection of bombesin (5.0 micrograms) significantly elevated circulating gastrin levels but did not affect circulating levels of CCK-33 and PP. Vagotomy did not alter gastrin release induced by intracerebroventricular injection of bombesin.

Animals↗

Overproduction of a gastrointestinal hormone, secretin, in Escherichia coli cells and its chemical characterization.

A cloned synthetic DNA fragment coding for 27-desamidosecretin (DAS), which differs from natural porcine secretin by the lack of the amide group at the carboxyl-terminal valine residue, was fused to the beta-galactosidase gene (lacZ) at the EcoRI site near the 3'-terminus of the gene. The fusion gene was efficiently expressed in Escherichia coli, yielding 1.15 X 10(6) fused-protein molecules per cell. After the treatment of the fused protein with cyanogen bromide, DAS was purified by a combination of ion-exchange column chromatography and reverse-phase high-performance liquid chromatography (HPLC). The structure of bacterial DAS was confirmed by tryptic mapping and amino acid composition analyses. The bacterial DAS was not amidated at its carboxyl-terminal valine residue. Nevertheless, it stimulated pancreatic secretion in rats as does authentic porcine secretin, indicating that the carboxyl-terminal amide is not essential to secretin activity.

Amino Acid Sequence↗

Production in Escherichia coli of biologically active secretin, a gastrointestinal hormone.

A synthetic gene for porcine secretin was ligated with Pst I-cleaved pBR322 by its flanking synthetic Pst I linkers to produce a fused protein consisting of an amino-terminal portion of beta-lactamase and an entire secretin molecule. The hybrid plasmid was transferred into competent Escherichia coli cells. The plasmids, which were proved in our investigation to contain the secretin gene in the desired orientation, were then screened for the production of secretin. This was shown by radioimmunoassay and gel electrophoretic analysis of the polypeptides that were synthesized in E. coli minicells transformed with the hybrid plasmids. Secretin so produced, whose carboxy terminal residue may not be amidated in contrast with natural porcine secretin, showed the same activity in stimulating pancreatic secretion in a bioassay with anesthetized rats as does natural secretin.

DNA Restriction Enzymes↗

Effect of small intestinal nutrient infusion on appetite, gastrointestinal hormone release, and gastric myoelectrical activity in young and older men.

OBJECTIVE: The mechanisms responsible for the reduction in appetite and slowing of gastric emptying in older persons are poorly understood. The aim of this study was to evaluate the effects of aging on small intestinal regulation of appetite, GI hormone release, and gastric myoelectrical activity. METHODS: Thirteen older (65-84 yr) and 13 young (18-32 yr) healthy men received isovolumetric, intraduodenal (i.d.) infusions of saline (control), lipid, and glucose for 120 min, on separate days. The energy content of the lipid and glucose infusions was identical at 2.86 kcal/min. Immediately after the i.d. infusions, each subject was offered a buffet meal, and ad libitum food intake was quantified. Blood glucose and plasma insulin, glucagon-like peptide 1, and glucose-dependent insulinotropic peptide were measured. Gastric myoelectrical activity was measured by surface electrogastrography (EGG). RESULTS: I.d. lipid suppressed food intake in both the young and older men (p < 0.05), whereas i.d. glucose suppressed food intake only in the older men (p < 0.05). The blood glucose (p < 0.01) and insulin (p < 0.05) responses to i.d. glucose were greater in older than young men. However, there were no differences in glucagon-like peptide 1 or glucose-dependent insulinotropic peptide responses to any of the infusions. There was a greater increase in the EGG power ratio both during and after i.d. glucose infusion in the young (p < 0.05) than the older men, and an attenuation of EGG frequency by nutrient infusions in older, but not young, men. CONCLUSIONS: Our findings indicate that aging is associated with nutrient-specific changes in appetite, hormonal, and gastric myoelectrical (EGG) responses to i.d. nutrients. An enhanced satiating effect of small intestinal carbohydrates may potentially contribute to the anorexia of aging.

Adolescent↗

Permeability of intestinal capillaries: effects of fat absorption and gastrointestinal hormones.

The purpose of this study was to determine whether the postprandial increase of intestinal lymphatic protein flux is due to an increased capillary permeability. Intestinal lymph flow and lymph (L) and plasma (P) protein concentrations were measured at various venous pressures under control conditions, after cream feeding, and during intraluminal perfusion with a bile-oleic acid solution. The osmotic reflection coefficient (sigma d), a measure of capillary permeability that is independent of surface area, was estimated under all conditions, assuming sigma d = 1 - L/P at high capillary filtration rates. The results acquired indicate that cream feeding and intraluminal perfusion with bile-oleic acid significantly increases intestinal capillary permeability. Pretreatment with indomethacin and antihistamines did not alter the permeability increase induced by intraluminal bile-oleic acid. Intra-arterial infusion of cholecystokinin and secretin did not increase intestinal capillary permeability. These studies indicate that the postprandial increase in intestinal lymphatic protein flux is due at least in part, to an increase in capillary permeability. Cholecystokinin, secretin, histamine, and prostaglandins do not appear to mediate the increased intestinal capillary permeability during fat absorption.

Animals↗

Gallbladder pressure-volume response to gastrointestinal hormones.

The pressure-volume (PV) response of the opossum gallbladder was studied under basal conditions and after the continuous intravenous infusion of gastrin I, secretin, and cholecystokinin (CCK). The hormone effects were examined individually and in combination. The unstimulated gallbladder was capable of accommodating increases in intraluminal volume with only slight changes in intraluminal pressure. Cholecystokinin significantly increased the pressure recorded from the gallbladder. The pressure generated depended on the concentration of CCK and the intraluminal volume. Gastrin I had no independent effect on the PV response of the gallbladder but reduced the stimulatory affect of CCK. Secretin, alone, decreased the PV response of the gallbladder. Secretin also antagonized the stimulatory response to CCK. These findings suggest that the regulation of gallbaldder motor function and pressure generation exclusive of neural input, may depend on the interaction of CCK with gastrin and secretin and the intraluminal volume of the organ at the time of stimulation.

Animals↗

Cholecystokinin receptor antagonist loxiglumide: influence on bilio-pancreatic secretion and gastrointestinal hormones in man.

We characterized the effect of the specific cholecystokinin (CCK) receptor antagonist loxiglumide (CR 1505) on gallbladder contraction, pancreatic enzyme output and plasma CCK concentrations determined by radioimmunoassay and bioassay. Gallbladder emptying and bilirubin output in response to the intraduodenal administration of a mixed liquid meal were completely inhibited by an intravenous infusion of loxiglumide (10 mg/kg/h). In contrast, meal-stimulated pancreatic enzyme secretion was diminished by only 30-40%. CCK concentrations in response to the test meal were 3-fold higher during infusion of loxiglumide, as determined by radioimmunoassay. In the absence of the antagonist, the bioassay measured CCK plasma levels identical to those determined by radioimmunoassay. In the presence of loxiglumide, CCK-like bioactivity was not detectable, indicating that the plasma concentrations of the CCK receptor antagonist were sufficient to abolish all circulating CCK-like bioactivity. We conclude that fasting volume and meal-induced contraction of the gallbladder are controlled by CCK. Postprandial pancreatic enzyme secretion, however, is mainly mediated by non-CCK-dependent mechanisms. Plasma CCK-like immunoreactivity is increased by loxiglumide, whereas plasma CCK-like bioactivity is zero in the presence of an CCK-receptor antagonist.

Adult↗