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C Beglinger

Publications and source records attributed to C Beglinger.

At least 91 records · Page 5Linked to original sources
PubMed1986

What is the maximal effective dose of caerulein in stimulating pancreatic secretion in man?

The pancreatic exocrine secretory response to increasing doses of exogenous caerulein with and without a background infusion of secretin was studied in 5 healthy volunteers. Caerulein over a full range of doses (2.3-37 pmol/kg/h) produced increasing enzyme secretion up to 18.5 pmol/kg/h, whereas 37 pmol/kg/h was clearly supramaximal and caused submaximal enzyme release. We conclude that maximal pancreatic enzyme secretion is achieved with lower caerulein doses than generally used in pancreatic function tests.

Adult↗
PubMed1986

Human pharmacological effects of SMS 201-995 on gastric secretion.

The inhibition of pentagastrin-stimulated-(3 micrograms kg-1 h-1) gastric acid secretion by various doses of intravenous and subcutaneous SMS 201-995, a somatostatin analogue, was investigated in healthy volunteers by means of gastric aspiration, using phenol red as a volume marker. The intravenous doses were compared with the standard dose of somatostatin-14, 3.5 micrograms kg-1 h-1. Similarly, SMS 201-995-induced inhibition of gastric acid secretion was compared with that of exocrine pancreatic secretion assessed by gastroduodenal aspiration. The results can be summarized as follows: SMS 201-995 is a potent inhibitor of gastric acid secretion, exerting near maximal inhibition at a dose of greater than or equal to 0.56 micrograms kg-1 h-1. Near maximal inhibition equals that achieved with SST-14 (3.5 micrograms kg-1 h-1). Pancreatic enzyme secretion appears to be strongly inhibited by lower doses of SMS 201-995 than gastric secretion. Single subcutaneous injections of SMS 201-995 produce an inhibition of gastric acid secretion lasting for many hours. Near maximal inhibition was obtained with a dose of 100 micrograms.

Adult↗
PubMed1985

[Interaction of the endo- and exocrine pancreas].

The pancreas has both exocrine and endocrine components. The exocrine component of the pancreas manufactures, stores, and packages digestive enzymes for digestion of food, whereas the endocrine secretes hormones that regulate the metabolism and utilization of the absorbed nutrient components. Both components are closely related, not only anatomically but also functionally. The available evidence to support the concept of a close interrelationship of endocrine and exocrine pancreatic function is summarized. It is shown that the endocrine part exerts a profound effect upon the digestive activities of the organ, and that impairment of endocrine function, such as diabetes, severely affects the exocrine component of the gland. Furthermore, dysfunction of the exocrine gland, as in chronic pancreatitis, progressively disturbs the function of the islet cell hormones. The interactions are governed by a complicated control system, the details of which are not yet clarified. As in any partnership, dysfunction of one partner severely affects the other and vice versa.

Animals↗
PubMed1985

Pancreatic enzyme response to a liquid meal and to hormonal stimulation. Correlation with plasma secretin and cholecystokinin levels.

Pancreatic trypsin output and plasma secretin and cholecystokinin (CCK) levels were measured in five healthy volunteers to investigate the mechanisms involved in regulating postprandial pancreatic secretion. The pancreas was stimulated by a liquid test meal or by either intravenous secretin (1-82 pmol/kg-1 per h-1) or caerulein, a CCK analogue (2.3-37 pmol/kg-1 per h-1), or by a combination of secretin and caerulein. Pancreatic secretion was assessed by a marker perfusion technique (polyethylene glycol [PEG 4000]), plasma secretin, and CCK by specific radioimmunoassays. Increasing doses of secretin produced increasing bicarbonate output (P less than 0.01), whereas trypsin was not stimulated over basal. Graded caerulein produced a stepwise increase in trypsin and bicarbonate output (P less than 0.01). Potentiation occurred for bicarbonate secretion between secretin and caerulein, but not for trypsin output. Postprandial trypsin secretion averaged 29.1 IU/min-1 over 150 min (equal to 55% of maximal response to caerulein). The peak trypsin response amounted to 90% of maximal caerulein. Significant increases of plasma secretion (P less than 0.05) and CCK (P less than 0.01) were observed after the meal. Comparison of enzyme and CCK responses to the testmeal or to exogenous caerulein suggested that the amount of CCK released after the meal could account for the postprandial trypsin secretion. We conclude that (a) the postprandial enzyme response in man is submaximal in comparison to maximal exogenous hormone stimulation; (b) CCK is a major stimulatory mechanism of postprandial trypsin secretion, whereas secretin is not involved; and (c) Potentiation of enzyme secretion is not a regulatory mechanism of the postprandial secretory response.

Adult↗
PubMed1984

Exocrine pancreatic secretion in response to a new CCK-analog, CCK33 and caerulein in dogs.

We studied the relative molar potencies of a newly synthetized cholecystokinin nonapeptide [Thr28,Nle31]CCK[25-33], natural porcine CCK33 and synthetic caerulein in conscious dogs with chronic gastric and pancreatic fistulas. Peptides were dissolved in albumin-containing solutions to prevent loss from solution. The three peptides were found to be equipotent on a molar basis in stimulating exocrine pancreatic secretion. As [Thr28,Nle31]CCK9 is a peptide less susceptible to oxidation than other forms of CCK, it is an interesting analog with many uses for medical and biological research.

Animals↗
PubMed1984

Effect of proglumide, a cholecystokinin receptor antagonist, on caerulein-stimulated pancreatic enzyme secretion and pancreatic polypeptide release in the dog.

In five conscious dogs we studied the effect of proglumide, a cholecystokinin (CCK) antagonist, on caerulein-stimulated pancreatic secretion and release of pancreatic polypeptide (PP). Graded doses of caerulein (15-240 ng/kg per h) were infused intravenously. Experiments were repeated with a fixed infusion of proglumide (40 mg/kg per h). Release of PP following increasing doses of caerulein was significantly inhibited by proglumide (P less than 0.01). However, proglumide did not significantly affect caerulein-stimulated pancreatic protein secretion. Proglumide might be useful in defining the physiological role of CCK.

Animals↗
PubMed1984

Interaction between stimulants of exocrine pancreatic secretion in dogs.

We measured bicarbonate and protein secretory responses to graded doses of intravenous caerulein and bethanechol and intraduodenal L-phenylalanine alone or with background secretin; graded doses of secretin alone or with background caerulein or L-phenylalanine; and background secretin plus graded doses of caerulein or L-phenylalanine plus background atropine sulfate. Potentiation (more-than-additive response) occurred for bicarbonate secretion between secretin and caerulein, between secretin and L-phenylalanine, but not between secretin and bethanechol. The only potentiating interaction for protein secretion was between secretin and low doses of caerulein. Atropine abolished the potentiated bicarbonate response to secretin plus L-phenylalanine but had no effect on the response to secretin plus caerulein. Potentiation between secretin and cholinergic mechanisms and cholecystokinin for pancreatic bicarbonate secretion may be an important regulatory mechanism, while potentiation of protein secretion with these stimulants does not appear to be important in dogs. A cholinergic mechanism mediates much of the bicarbonate potentiation between secretin and intestinal L-phenylalanine.

Animals↗
PubMed1984

Pancreatic polypeptide inhibits exocrine pancreatic responses to six stimulants.

We determined the effects of three different doses of pancreatic polypeptide (50, 200, and 800 pmol X kg-1 X h-1) on pancreatic responses to graded doses of intravenous secretin, caerulein, and bethanechol and intraduodenal HCl, L-phenylalanine, and sodium oleate in dogs. The two lowest doses of pancreatic polypeptide (PP), which produced blood levels lower than measured after a meal, significantly inhibited the pancreatic responses to secretin, caerulein, HCl, and L-phenylalanine; the highest dose of PP inhibited the responses to bethanechol and sodium oleate. There was no difference in the degree of inhibition of bicarbonate or protein secretion caused by pancreatic polypeptide. With secretin, caerulein, bethanechol, and sodium oleate, inhibition was most pronounced against lower doses and was surmountable with higher doses of these stimulants. Inhibition of responses to HCl and L-phenylalanine was observed at all doses of these stimulants. Inhibition of the exocrine pancreatic secretory responses to six different stimulants by PP suggests that this hormone may play an important role in regulation of postprandial pancreatic secretion.

Animals↗
PubMed1984

Plasma secretin and pancreatic response to various stimulants including a meal.

In dogs with gastric and duodenal Thomas cannulas, we investigated the threshold dose range of exogenous secretin and intraduodenal HCl for pancreatic bicarbonate secretion and, with a recently developed radioimmunoassay, measured the increase in plasma secretin concentrations. Synthetic secretin (2.5, 7.5, and 22.5 ng X kg-1 X h-1) was dissolved in saline or 0.1% dog albumin and given with or without a background infusion of 30 ng X kg-1 X h-1 of caerulein. The minimal dose of secretin that elicited a significant pancreatic bicarbonate response as well as an increase in plasma secretin concentration was 7.5 ng X kg-1 X h-1 when administered with albumin and 22.5 ng X kg-1 X h-1 without albumin. The threshold dose for duodenal HCl was 2 mmol X h-1. The threshold secretin dose for bicarbonate secretion and for an increase in plasma secretin levels was unchanged with a background caerulein infusion. Furthermore, postprandial secretin concentrations were measured. After a meat meal plasma secretin release appeared to occur in spikes up to 10 pmol X l-1 corresponding to secretin levels seen during infusion of 7.5 ng X kg-1 X h-1 of secretin and intraduodenal acid perfusion at a dose of 2 mmol X h-1.

Animals↗
PubMed1984

Bioactivity of cholecystokinin analogues: CCK-8 is not more potent than CCK-33.

We determined the relative molar potencies of structural analogues of porcine cholecystokinin (CCK-39, CCK-33, CCK-8, and caerulein). Peptide concentrations delivered in infusates or present in bathing medium were measured by radioimmunoassay. The presence of albumin prevented loss of CCK-39 and CCK-33 from solution to a greater degree than loss of CCK-8 and caerulein from solution. As much as 10-fold differences in CCK-33 and CCK-39 concentrations were seen in albumin-containing versus nonalbumin-containing infusates. The potency estimates calculated from radioimmunoassay-corrected concentrations with CCK-8 as standard (potency 1.00) were canine pancreatic secretion in vivo: CCK-39 4.1, CCK-33 2.2, and caerulein 2.1; rat pancreatic secretion in vivo: CCK-39 2.1, CCK-33 5.4, and caerulein 5.4; rat pancreatic secretion in vitro: CCK-33 1.7, and caerulein 1.2; guinea pig gallbladder contraction in vivo: CCK-33 1.3, and caerulein 0.9; and guinea pig gallbladder contraction in vitro: CCK-33 1.8, and caerulein 5.8. Our data indicate that CCK-8 is not more potent than longer analogues and suggest that larger forms of CCK may be important mediators of the biological actions of CCK.

Albumins↗
PubMed1984

Pancreatic polypeptide release: role of stimulants of exocrine pancreatic secretion in dogs.

There are apparent similarities in the mechanisms of the intestinal phase of exocrine and pancreatic polypeptide (PP) secretion by the pancreas. To characterize this relationship, we measured incremental responses of protein, bicarbonate, and PP to graded doses of intravenous secretin, caerulein, CCK8, CCK33, bethanechol, and intraduodenally perfused HCl, sodium oleate, and L-phenylalanine in dogs with gastric and pancreatic fistulas and compared them with average postprandial values. Secretin did not release PP at any dose studied, whereas intraduodenal HCl increased PP levels slightly at a load maximal for pancreatic secretion. Caerulein produced dose-related increases in PP secretion (maximal, 106% of meal response) but CCK8 and CCK33 had much less effect at doses equivalent for protein secretion. Bethanechol was a weak stimulant for PP only at the largest tolerable dose. L-Phenylalanine and sodium oleate markedly increased protein secretion, but only oleate clearly stimulated PP. Our results suggest a greater quantitative importance of the intestinal phase for exocrine than endocrine (PP) pancreatic secretion.

Animals↗
PubMed1984

The effect of an octapeptide somatostatin analogue (SMS 201-995) and somatostatin-14 (SST-14) on pentagastrin-stimulated gastric acid secretion: a comparative study in man.

Using an open, randomised study design, the efficacy and tolerance of SMS 201-995 (a synthetic octapeptide SST-14 analogue with a plasma half-life of 45 min) was compared with that of SST-14 in inhibiting pentagastrin-stimulated gastric acid secretion. In 10 healthy volunteers gastric acid secretion was stimulated for 3.5 hours by an infusion of 3 microgram kg-1 h-1 pentagastrin. One hour after the start of pentagastrin a 2-hour i.v. infusion of either SST-14 (3.5 microgram kg-1 h-1) or one of 4 dosages of SMS 201-995 (0.14, 0.28, 0.56 or 1.12 microgram kg-1 h-1) was started. SMS 201-995 inhibited acid secretion in a dose-dependent manner. The inhibition achieved with the 0.56 and 1.12 microgram kg-1 h-1 dosages was comparable with that obtained with 3.5 microgram kg-1 h-1 SST-14. SMS 201-995 (1.12 microgram kg-1 h-1) appeared to have a longer duration of action than SST-14. No side effects were recorded under either of the test substances.

Adult↗
PubMed1983

[Endocrinology of exocrine pancreas function].

Recent advances in knowledge of the hormonal control of exocrine pancreatic secretion are discussed in the light of two main mechanisms of action: first, the effect of the main regulatory peptides on the exocrine pancreas, and second, the inhibitory mechanisms which may affect pancreatic secretion. A synthesis of the regulatory principles controlling exocrine pancreatic secretion is attempted.

Amino Acid Sequence↗
PubMed1983

Effect of adding albumin to solutions of somatostatin on inhibiting pentagastrin-stimulated acid secretion in dogs.

In five conscious dogs with chronic gastric fistulas we studied the effect of somatostatin solutions on pentagastrin-stimulated acid secretion. Somatostatin was dissolved in 0.154 M NaCl alone or in the same amount of saline to which dog albumin had been added to give a 0.5% solution. Somatostatin produced a dose-dependent inhibition of pentagastrin-stimulated gastric secretion. However, the inhibition was significantly less when somatostatin was dissolved in saline as compared to saline plus albumin. This study suggests that albumin should be added to somatostatin solutions to preserve biological activity, and it confirms previous reports indicating that, without albumin, basic peptides have a tendency to stick to infusion systems.

Albumins↗