Pancreatic exocrine secretion in the rat after chronic alcohol ingestion: nonparallel secretion of proteins and pancreatic secretory trypsin inhibitor

Pancreatic secretion was studied in rats given 20% (v/v) ethanol or water ad libitum for 7--8 months. Basal secretion samples were collected for 30 min, after which secretion was stimulated with secretin (1.1 U/h) and cholecystokinin-pancreozymin (2.8 U/h). Then, four successive 30-min samples were collected. The flow rate, protein concentration and output, pancreatic secretory trypsin inhibitor (PSTI) concentration and output, and chymotrypsinogen concentration increased significantly from basal levels during the first stimulation period in both groups, with no significant differences between the groups. During the second, third, and fourth stimulation periods gradual decreases of these parameters were observed in both groups, and the decrease of volume, protein output, and PSTI output were significantly greater in the alcohol group than in the control group. No significant differences were observed in the concentrations of chymotrypsinogen, protein, and PSTI, but the PSTI/protein ratio was significantly lower in the alcohol group at the end of the experiment. The concentrations of bicarbonate did not decrease during stimulation and were elevated in the alcohol group compared with the control group during the fourth period. It is suggested that the decreased PSTI/enzyme ratio caused by long-term alcohol ingestion might favour premature activation of the proenzymes in the pancreatic ducts.     

Effect of ursodeoxycholate on pancreatic exocrine secretion in vitro and in vivo study]

In the present study, we examined the effect of ursodeoxycholate (UDCA) and it's taurine conjugate (TUDC) on rat pancreatic exocrine secretion using dispersed pancreatic acini (in vitro) and conscious rats (in vivo). In in vitro study 300 microM UDCA significantly increased 10(-12)-10(-9) M CCK-8 stimulated amylase release and change of intracellular Ca2+ concentration, but TUDC did not have these effects. In in vivo study intraduodenal infusion of UDCA but not TUDC stimulated pancreatic exocrine secretion. Intravenous infusion of secretin antibody decreased bicarbonate output, however, this increase was not prevented by CCK antagonist. Thus, it was suggested that UDCA has direct action on pancreatic acini and UDCA infused intraduodenally stimulates pancreatic secretion, possibly via the release of a secretin-like substance. The taurine conjugate has weak bioactivity on pancreatic exocrine secretion in both in vitro and in vivo.     

Pirenzepine inhibits pancreatic exocrine secretion in the rat

Pirenzepine is a newly developed anticholinergic drug that reduces gastric acid secretion and is therefore used in Europe and Japan to treat patients with peptic ulcer. The inhibitory effect of pirenzepine on pancreatic exocrine function and its reversibility were studied in the isolated pancreatic acini and the isolated perfused pancreas of rats. In the isolated acini, pirenzepine caused a concentration-dependent rightward shift in the dose-response curve for carbamylcholine-stimulated amylase secretion without altering the maximal increase. Addition of 10 microM pirenzepine at the beginning as well as after 10 or 20 min of stimulation with 1 microM carbamylcholine rapidly abolished pancreatic secretions in both the isolated acini and isolated perfused pancreas. The inhibitory effect of pirenzepine was fully reversible in the isolated acini, whereas pirenzepine caused a small residual inhibition on pancreatic exocrine secretion in the isolated perfused pancreas. These results suggest the existence of pirenzepine-sensitive receptors in the pancreatic vagal pathway at a site remote from the acinar cell. The present data indicate that pirenzepine may have an influence on pancreatic exocrine function by inhibiting not only acinar cell cholinergic receptor but also endogenous cholinergic activity of the pancreas when a large dose is given.     

Calcium-chlorotetracycline fluorescence and pancreatic exocrine secretion in the rat

The fluorescence and secretory response of calcium-chlorotetracycline were simultaneously and continuously measured in isolated perfused rat pancreata. Continuous vascular perfusion with 10 microM chlorotetracycline increased the fluorescence intensity exponentially. Continuous stimulation with higher nonphysiological doses of CCK (20 mU/ml) or ACh (10(-6) M) induced a gradual decrease in the Ca-cholorotetracycline fluorescence which increased to control after cessation of the stimulation, and secretory response, consisting of an initial rapid ascent followed by a decline. On the other hand, continuous stimulation with a lower concentration of CCK (5 mU/ml) or ACh (5 X 10(-8) M), which seems to be rather physiological, did not change the time course of the Ca-chlorotetracycline fluorescence increase, but it evoked a definite secretory response, consisting of an initial rapid ascent to a maximum followed by a descent to a sustained plateau. In a Ca2+-deficient environment, stimulation with 5 mU CCK/ml evoked only a small secretory response and a gradual insignificant decrease in the Ca-chlorotetracycline fluorescence. The present results may support the view that continuous stimulation with secretagogues at physiological concentrations does not cause dissociation of stored Ca2+ from intracellular sites but does initiate secretion probably via the rise in [Ca2+]i induced by the influx of extracellular Ca2+.     

A radioimmunoassay for rat pancreatic secretory trypsin inhibitor

A radioimmunoassay for the detection of pancreatic secretory trypsin inhibitor (PSTI) in the rat is described. The sensitivity of the assay enables the specific measurement of this inhibitor in the serum of normal rats. The average base-line value for multiple animal serum specimens taken from fasting female Wistar rats being fed conventional diets was 11.6 +/- 6.2 micrograms/l. The inhibitor existed in its free form in serum, and PSTI immunoreactivity increased significantly within 2 h of the induction of experimental pancreatitis. The present assay will facilitate the study of PSTI in experimental diseases of the pancreas.     

Depression of pancreatic exocrine secretion with a carbonic anhydrase inhibitor

Digestive Diseases and Sciences - Diamox, a carbonic anhydrase inhibitor, was found to be an effective pancreatic exocrine secretory depressant. In 2 patients with pure pancreatic fistulas, Diamox...     

Effects of L-364,718 on pancreatic exocrine and endocrine secretion in the rat.

We examined the inhibitory effect of L-364,718, a nonpeptide cholecystokinin (CCK) antagonist, on CCK stimulation of pancreatic exocrine and endocrine secretion in both the isolated pancreatic acini and the isolated perfused pancreata of rats. In the isolated acini, L-364,718 inhibited CCK octapeptide (CCK-8)-stimulated amylase release and binding of 125I-CCK-8 in a dose-dependent manner without appreciable effects on the basal amylase secretion. L-364,718 also inhibited amylase release in response to caerulein and gastrin I, but had no effect on amylase release stimulated by other secretagogues or by agents bypassing receptors. Similarly, binding of N-methylscopolamine to pancreatic acini was not inhibited by L-364,718. In the isolated perfused pancreata, L-364,718 inhibited CCK-8-stimulated pancreatic exocrine secretion and insulin release. The inhibitory effects of L-364,718 were more potent for insulin release than for exocrine secretion and persisted even after the removal of L-364,718 infusion. These results clearly demonstrate that L-364,718 is a specific, potent, and prolonged antagonist of CCK's stimulatory actions on pancreatic acinar and B cells.     

Changes in pancreatic exocrine secretion with age: pancreatic exocrine secretion does decrease in the elderly.

Pancreatic exocrine secretion was estimated in 180 normal control patients, free of abdominal and pancreatic disease, aged from 16 to 83 years. Duodenal juice was collected in two 15-min fractions after a single intravenous injection of 1 U/kg secretin + 3 U/kg CCK. Volume, maximal concentration and output of bicarbonate, lipase, phospholipase and chymotrypsin were estimated as well as minimal concentration and output of chloride and calcium. Each parameter was plotted against age, either individually or after separation into two age groups. Volume linearly increased up to the 3rd decade, and thereafter linearly decreased. Bicarbonate secretion paralleled fluid secretion and also decreased after the 3rd decade. The changes in chloride and calcium concentrations were different: concentrations linearly increased after the 3rd decade. Calcium concentration linearly increased with age (p less than 0.02) while chloride output was unchanged. The three enzymes that were studied linearly decreased in concentration as well as in output with age from the 3rd decade (p less than 0.02). Protein secretion decreased before water and bicarbonate secretion. One can conclude that pancreatic secretion changes in humans with age. Aging alters pancreatic secretion, through a decrease in flow rate, bicarbonate and enzyme secretion while calcium concentration is enhanced. Although not requiring substitutive therapy in the whole population, individual cases of pancreatic exocrine insufficiency might be explained by aging, without malnutrition.     

Plasma osmolality and exocrine pancreatic secretion

To confirm the influence of plasma osmolality on exocrine pancreatic secretion, hypertonic saline (4% saline) was given intravenously to dogs with gastric and pancreatic fistulae. Intravenous administration of hypertonic saline caused a reduction of pancreatic juice flow and bicarbonate output, but did not alter protein output stimulated by secretin and cerulein. The changes of pancreatic juice flow(X) exhibited negative correlations with the changes in plasma osmolality(Y)(Y = -2.2X + 6A, r = -0.74,p < 0.01). Plasma osmolality and plasma vasopressin level were measured simultaneously. Plasma osmolality was elevated from 292 to 315 mOsm/kg with concurrent increase of plasma vasopressin level from 2.4 to 19.6 pg/ mL. On the other hand, exogenous administration of vasopressin inhibited pancreatic juice flow and bicarbonate output dose-dependently. In conclusion, elevation of plasma osmolality decreased exocrine pancreatic secretion stimulated by secretin and cerulein, and vasopressin may play an important role in its mechanism.     

Plasma osmolality and exocrine pancreatic secretion

To confirm the influence of plasma osmolality on exocrine pancreatic secretion, hypertonic saline (4% saline) was given intravenously to dogs with gastric and pancreatic fistulae. Intravenous administration of hypertonic saline caused a reduction of pancreatic juice flow and bicarbonate output, but did not alter protein output stimulated by secretin and cerulein. The changes of pancreatic juice flow(X) exhibited negative correlations with the changes in plasma osmolality(Y) (Y = -2.2X + 6.4, r = -0.74, p less than 0.01). Plasma osmolality and plasma vasopressin level were measured simultaneously. Plasma osmolality was elevated from 292 to 315 mOsm/kg with concurrent increase of plasma vasopressin level from 2.4 to 19.6 pg/mL. On the other hand, exogenous administration of vasopressin inhibited pancreatic juice flow and bicarbonate output dose-dependently. In conclusion, elevation of plasma osmolality decreased exocrine pancreatic secretion stimulated by secretin and cerulein, and vasopressin may play an important role in its mechanism.     

Inhibitory effects of the cholecystokinin antagonist loxiglumide on pancreatic exocrine secretion and pancreatic growth in conscious rats.

The effects of cholecystokinin (CCK) receptor antagonist Loxiglumide (CR 1505) on pancreatic exocrine secretion and growth stimulated by chronic bile-pancreatic juice diversion to the ileum were studied in conscious rats. Pancreatic secretion was measured each day at 0900 h for 7 d. Pancreatic flow and protein output were significantly increased 24 h after bile-pancreatic juice diversion. Protein output increased each successive day, reaching maximal values of 3.6-fold above basal by the 6th and 7th d of chronic bile-pancreatic juice diversion. Fluid output reached maximal values of approx. 3.5-fold above basal by the 3rd d of chronic bile-pancreatic juice diversion. Plasma CCK increased threefold above basal levels after 24 h of bile-pancreatic juice diversion and remained three- to fourfold above basal. Intragastric bolus infusion of CR 1505 (50 mg/kg) on the 7th d of chronic bile-pancreatic juice diversion inhibited pancreatic protein and fluid secretion by 80 and 75%, respectively, 60 min after administration and by 52 and 71%, respectively, 5 h later. Pancreatic wet wt after 7 d of chronic bile-pancreatic juice diversion was significantly increased by 56%, and this was completely suppressed by 50 mg/kg of CR 1505 given intragastrically every 12 h. These rests indicate that the rat with chronic bile-pancreatic juice diversion is a useful model to examine both potency and duration of the action of CCK receptor antagonists and show that CR 1505 inhibits pancreatic exocrine secretion and growth induced by endogenous CCK.     

Allopurinol stimulates pancreatic exocrine secretion in the dog

The effects of allopurinol on the secretion of pancreatic juice were investigated both in live animals and in preparations of isolated, blood-perfused dog pancreas and were compared with those of secretin. An i.v. administration of allopurinol (3-10 mg/kg) caused a dose-dependent increase in the pancreatic secretion. The secretory responses to 3 and 10 mg/kg of allopurinol were approximately equal to those to 0.03 and 0.1 U/kg of secretin, respectively. An intra-arterial (i.a.) infusion of allopurinol (0.5-1.2 mg/min) also elicited dose-dependent increases in flow rates, bicarbonate concentrations, and outputs of pancreatic exocrine secretion, but protein concentrations were little affected by allopurinol. Similar results were obtained in the juice induced by an i.a. infusion of secretin (0.012-0.05 U/min). Both bicarbonate and protein concentrations in the juice obtained with allopurinol were almost the same as those obtained with secretin at a similar flow rate of pancreatic secretion. The secretory activities at 0.5, 1.0, and 1.2 mg/min of i.a. allopurinol infusion corresponded roughly to those at 0.012, 0.025, and 0.05 U/min of i.a. secretin infusion, respectively. Therefore, the secretory action of allopurinol was similar to that of secretin. The allopurinol-induced secretion was not modified by pretreatment with atropine sulfate, cimetidine, or sulpiride hydrochloride. These results suggest that allopurinol stimulates pancreatic secretion by acting directly on ductular cells of the dog pancreas.