Neurohormonal control of human pancreatic exocrine secretion.
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Acetylcholine↗
Biomedical subjects
M Katschinski
Publications and source records attributed to M Katschinski.
Gastrointestinal motor and secretory responses to cholinergic stimulation in humans. Differential modulation by muscarinic and cholecystokinin receptor blockade.
The present study investigated how a cholinergic agonist modifies interdigestive motility and secretion of the upper gastrointestinal tract and how muscarinic and cholecystokinin receptor blockade interfere with this direct cholinergic stimulation. In eight healthy volunteers, gastrointestinal motor and secretory responses to bethanechol (12.5, 25, and 50 micrograms kg-1 h-1) with and without a background of atropine (5 micrograms kg-1 h-1) or loxiglumide (10 mg kg-1 h-1) were studied. Stepdoses of bethanechol caused a parallel stimulation of antroduodenal motility and gastropancreatic secretion (P < 0.01) without inducing a fed pattern. However, duration of phase I was shortened (P < 0.05). Only high doses of bethanechol enhanced gastrin (P < 0.05), cholecystokinin (P < 0.05), and pancreatic polypeptide (P < 0.01) release. Atropine completely antagonized motor and secretory responses to cholinergic stimulation. Loxiglumide left cholinergically stimulated motility and pancreatic enzyme secretion unaltered. With co-infusion of bethanechol and loxiglumide, PP release dropped by 63% (P < 0.01); gastric acid output, gastrin and CCK release increased by 56%, 16%, and 25%, respectively (P < 0.05). We conclude that stimulation by a cholinergic agonist preserves the interdigestive pattern. Low dose muscarinic receptor blockade abolishes cholinergic stimulation over the full dose range. Inhibition of somatostatin release would explain stimulation of gastrin release and gastric acid secretion with co-infusion of bethanechol and loxiglumide. Endogenous CCK appears to interact with direct cholinergic stimulation at the pancreatic PP cell and the gastric D-cell but not at pancreatic acinar and antroduodenal smooth muscle cells.
Adult↗
Cisapride stimulates human esophageal motility.
The potency of cisapride to stimulate esophageal motility is still a matter of conjecture. This double-blind placebo-controlled study assessed the effect of repeated oral doses of cisapride at 10 and 20 mg on interdigestive esophageal motility in 10 healthy male volunteers. In each experiment, esophageal motility was recorded continuously for 60 min with a sleeve sensor straddling the lower esophageal sphincter and four series of 10 wet swallows being performed. Analysis of motor events was computer assisted. Plasma cisapride levels amounted to 72.3 +/- 6.1 ng/ml with 10 mg cisapride and 142.5 +/- 11.9 ng/ml with 20 mg cisapride (p < 0.001 vs. 10 mg). Lower esophageal sphincter pressure increased from 20.6 +/- 2.3 mm Hg (placebo) to 28.9 +/- 2.3 mm Hg with 10 mg cisapride (p < 0.0001 vs. placebo) and to 26.8 +/- 1.8 mm Hg with 20 mg cisapride (p < 0.001 vs. placebo). Cisapride increased amplitude, duration, and area but not contractility and peristaltic velocity of esophageal contraction waves. Cisapride caused a maximum rise in amplitude of 22.4%, in area of 19.4%, and in duration of 9.6%. Its effects were greatest in the proximal and middle smooth muscle segments and more pronounced with 10 than with 20 mg. We conclude that cisapride clearly increases lower esophageal sphincter pressure and, to a lesser extent, raises amplitude and prolongs duration of esophageal contraction waves. Effects on contraction waves seem to correlate with the density of cholinergic innervation. Increasing the dose above 10 mg in the steady state does not further enhance the effect in healthy subjects.
Administration, Oral↗
Ulcerative colitis and Crohn's disease: factor XIII, inflammation and haemostasis.
An important role has been ascribed to plasma factor XIII (FXIII) in inflammation and wound healing. FXIII is necessary for fibrin stabilization and interacts with connective tissue and adhesive proteins and cells. In a prospective study, FXIII activity and parameters of coagulation, fibrinolysis and inflammation, were determined in patients with ulcerative colitis (UC; 13 active, 22 moderate) and Crohn's disease (CD; 36 active, 45 moderate). FXIII levels were lower in active than in moderate UC and CD, and were < 70% of normal values in 7/13 patients with active UC, and in 7/36 patients with active CD, although the median values did not fall below the normal range. FXIII was somewhat higher in active UC patients responding to therapy. The FXIII levels were widely scattered, and low values appear to be due to greatly enhanced turnover. A correlation between FXIII and the systemic levels of markers of activation of haemostasis and inflammation was lacking, but there was a correlation with the extent of bowel involvement. FXIII levels were lower in the patients with involvement beyond the sigmoid colon in CU (p = 0.0045), and both small and large bowel segments in CD (p = 0.0223) patients. This points to local consumption and/or loss of FXIII within the inflamed tissue, and provides an argument for FXIII substitution in the treatment of acute episodes of inflammatory bowel diseases.
Adolescent↗
The effect of cisapride and metoclopramide on human digestive and interdigestive antroduodenal motility.
BACKGROUND: To date, there is little information available about the effect of cisapride and metoclopramide on gastroduodenal pressure waves and their space/time orientation. METHODS: Antroduodenal pressures (two antral, three duodenal recording sites) were measured in nine healthy volunteers. Cisapride (10 mg), metoclopramide (10 mg), and placebo were administered intravenously on different days in a randomized manner. RESULTS: During the interdigestive state cisapride increased the motility index significantly in the antrum (p < 0.05) and duodenum (p < 0.005), metoclopramide only in the duodenum (p < 0.01). Antroduodenal coordination was significantly (p < 0.01) improved by cisapride but not by metoclopramide. There is evidence of antroduodenal coordination even during the interdigestive state. After a liquid test meal an increase in the antroduodenal motility index (p < 0.05), in the rate of prograde antroduodenal peristalsis (p < 0.01), and in antroduodenal coordination (p < 0.01) was caused by cisapride but not metoclopramide. Both prokinetics decreased (p < 0.01) retrograde antroduodenal peristalsis. CONCLUSION: Cisapride significantly improves antroduodenal coordination and antroduodenal motility; metoclopramide seems to be less effective.
Adult↗
Induction of the fed pattern of human exocrine pancreatic secretion by nutrients: role of cholecystokinin and neurotensin.
The aim of the present study was to assess the role of cholecystokinin and neurotensin in converting the cyclical interdigestive pattern of pancreatic secretion into the non-cyclical fed pattern. Six healthy male volunteers were studied on 4 separate days. During each experiment a mixed liquid meal or solutions of individual nutrients were perfused intraduodenally for 180 min at 2 ml/min. The mixed meal contained 4.3 g glucose, 2.0 g fractionated soya oil, and 1.7 g casein hydrolysate per 100 ml, which delivered a caloric load of 0.9 kcal/min into the duodenum. The isocaloric and isotonic solutions of individual nutrients contained 44.5 g glucose, 17.8 g fractionated soya oil, or 44.5 g hydrolysed serum bovine albumin per liter and delivered 0.36 kcal/min into the duodenum. Duodenal aspirates and blood samples were collected at regular intervals for determination of pancreatic enzyme outputs and plasma levels of cholecystokinin and neurotensin, respectively. The mixed meal converted the cyclical interdigestive secretory pattern into the noncyclical fed pattern whereas none of the three individual nutrients abolished the interdigestive pattern. Not only the mixed meal but also lipid and protein perfusion consistently stimulated cholecystokinin release. Integrated incremental cholecystokinin release amounted to 32.3 +/- 9.9 pg/ml x 180 min with the mixed meal, 23.2 +/- 6.5 with lipid perfusion (P < 0.05 versus mixed meal) and 13.4 +/- 3.8 with protein perfusion (P < 0.05 versus mixed meal). The carbohydrate solution did not significantly release cholecystokinin. None of the duodenal perfusates raised neurotensin plasma levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Cephalic stimulation of gastrointestinal secretory and motor responses in humans.
The present study was designed (a) to investigate the cephalic phase of gastropancreatic secretion, antroduodenal motility, and regulatory peptide release in six healthy young men and (b) to assess its regulation by the cholinergic system and endogenous cholecystokinin. Sham feeding performed for 15 minutes induced a concurrent stimulation of gastropancreatic secretion, antroduodenal motility, and pancreatic polypeptide release that lasted for 30 minutes. Reappearance of interdigestive phases III was retarded in the post-sham-fed state. Atropine abolished secretory, motor, and pancreatic polypeptide responses to sham feeding and enhanced gastrin release. The cholecystokinin receptor antagonist loxiglumide did not attenuate pancreatic enzyme response but diminished antral motor response by 72% (P less than 0.05) and release of pancreatic polypeptide by 91% (P less than 0.05); it enhanced gastrin release and abolished retardation of reappearance of phase III with sham feeding. It is concluded that (a) there is a distinct cephalic phase of gastropancreatic secretion, antroduodenal motility, and pancreatic polypeptide release in humans that is primarily under cholinergic control and that (b) endogenous cholecystokinin is involved in antral motor, gastrin, and pancreatic polypeptide responses to sham feeding.
Adult↗
[Conservative treatment of florid peptic esophageal stenosis. Complete elimination by dilatation and omeprazole in H2-blocker refractory cases].
23 patients with severe reflux oesophagitis complicated by peptic erosive strictures requiring dilatation and resistant to H2-blocker therapy were treated with the proton pump inhibitor omeprazole (initial dosing: 40 mg daily) and dilated. Combination of dilatations (median 2, range 1 to 12 courses) and omeprazole therapy facilitated complete resolution of strictures and disappearance of peptic lesions after four and eight weeks in 30% and 70%, respectively. In all remaining cases healing could be achieved by perpetuation of omeprazole therapy though three patients (13%) required omeprazole doses higher than 40 mg daily for healing and maintenance. Follow-up investigations available in 17 patients during continuation of omeprazole therapy revealed no recurrence of strictures. It is concluded that more pronounced and particularly longer lasting inhibition of acid secretion is effective even in these most severe cases of reflux oesophagitis.
Adolescent↗
[Electrochemical measuring system for the registration of transmucosal gastrointestinal potential differences].
An electrochemical measuring system for the recording of transmucosal gastrointestinal potential differences based on silver electrodes with double-junctions and continuous-flow saline bridges is described. Under bioelectrochemical control, a probe can passed from the esophagus via the stomach into the duodenum can be accurately assigned to each of these three segments of the intestine. Measurements are demonstrated and applications discussed.
Animals↗
[Mechanisms of postprandial stimulation of gastrointestinal motility and pancreatic secretion].
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Animals↗
Myoelectric and manometric patterns of human rectosigmoid colon in irritable bowel syndrome and diverticulosis.
Rectosigmoid electric control activity and intraluminal pressure were measured in the fasting state and after a standard 3040-kJ meal in irritable bowel syndrome (IBS) patients (n = 41), diverticulosis patients (n = 15), and healthy controls (n = 13). Analysis of myoelectric and motor patterns was performed computer-based with home-made software. Spectral analysis (fast Fourier transform) and computer recognition of slow waves emulating visual scoring showed very similar slow-wave frequency patterns in all three groups. Calculation of contractile indices displayed a widely scattered variable of motility in all three groups without significant differences. IBS subgroups with different bowel patterns showed very similar frequencies of basic myoelectric rhythm and a considerable overlap of contractile activity without significant differences among the subgroups and compared with controls. Slow-wave rhythm seems unlikely to be the basis of disturbed motility in IBS and diverticular disease. A specific pattern of contractile activity was not detectable in either condition.
Adult↗