Effect of pancreatic proteases on plasma cholecystokinin, secretin, and pancreatic exocrine secretion in response to sodium oleate

Chey

American Journal of Physiology-Gastrointestinal and Liver Physi

2000

Long-chain fatty acids are potent stimulants of secretin and CCK release. The cellular mechanisms of fatty acid-stimulated secretion of these two hormones are not clear. We studied the stimulatory effect and mechanism of sodium oleate (SO) on secretin- and CCK-producing cells. SO stimulated the release of secretin or CCK from isolated rat mucosal cell preparations enriched in either secretin- or CCK-producing cells, respectively. SO also time- and dose-dependently stimulated secretin and CCK release from STC-1 cells. In STC-1 cells, SO-stimulated secretin and CCK release was potentiated by IBMX and inhibited by a protein kinase A-selective inhibitor and a cAMP-specific antagonist. SO-stimulated releases of the two hormones were also inhibited by downregulation or inhibitors of protein kinase C, a calmodulin antagonist and an inhibitor of calmodulin-dependent protein kinase II. Chelating of extracellular Ca(2+) or addition of an L-type calcium channel blocker diminished SO-stimulated hormone releases. SO caused an increase in intracellular Ca(2+) concentration that was partially reversed by diltiazem but had no effect on production of cAMP, cGMP, or inositol-1,4,5-triphosphate. These results indicate that SO acts on secretin- and CCK-producing cells. Its stimulatory effect is potentiated by endogenous protein kinase A and mediated by activation of Ca(2+) influx through the L-type channels and of protein kinase C and Ca(2+)/calmodulin-dependent protein kinase II.

mentioning

confidence: 99%

Cellular mechanism of sodium oleate-stimulated secretion of cholecystokinin and secretin

Chey

American Journal of Physiology-Gastrointestinal and Liver Physi

2000

“…However, when the increase in pancreatic secretion was reversed by either pancreatic juice or trypsin in the duodenum, the increases in plasma concentration of CCK (3)(4)(5) and secretin (6) were also abolished in rats. Recently, in rats, it was learned that the increases in both pancreatic exocrine secretion and plasma concentrations of secretin and CCK in response to intraduodenal administration of sodium oleate was suppressed significantly by either pancreatic juice or a combination of both trypsin and chymotrypsin (7). However, interestingly, in similar experiments in dogs (8), pancreatic juice or trypsin caused significant decreases in both pancreatic secretion and plasma concentration of secretin but no decrease of CCK.…”

mentioning

confidence: 99%

Mechanism of acid-induced release of secretin in rats. Presence of a secretin-releasing peptide.

Li¹,

Lee²,

Chang³

et al. 1990

J. Clin. Invest.

American Journal of Physiology-Gastrointestinal and Liver Physi

“…acinar cell proliferation; cholecystokinin antagonist; endogenous cholecystokinin release IT IS WELL KNOWN THAT the presence of trypsin and chymotrypsin in the proximal small intestine exerts a negative feedback regulation on pancreatic exocrine secretion in rats (5,8,16,20,40), guinea pigs (15), pigs (11), and humans (13,19,22,32,33). Inhibition of luminal proteolytic activities by intraduodenal infusion of soybean or synthetic trypsin inhibitors (6,8,19,30,31,40) or intact protein (17,18) or by diversion of biliary-pancreatic secretions away from the small intestine (5,8,20) has been shown to increase plasma concentrations of cholecystokinin (CCK) (6,16,30,40) and secretin (31,40) and to strongly stimulate pancreatic exocrine secretion (6,16,30,40). In our previous studies (29,30), we have demonstrated that an oral administration of the synthetic trypsin inhibitor camostat mesylate has two different stimulatory effects, immediate and delayed, on pancreatic fluid secretion.…”

mentioning

confidence: 99%

CCK-, secretin-, and cholinergic-independent pancreatic fluid hypersecretion in protease inhibitor-treated rats

Yamamoto

Shirohara

Ōtsuki

1998

Plasma cholecystokinin (CCK) levels in fed rats increased from 2.59 ± 0.13 pmol/l to the peak of 27.6 ± 4.1 pmol/l at 1 h after a single oral administration of synthetic protease inhibitor (PI; ethyl N-allyl- N-{( E)-2-methyl-3-[4-(4-amidino-phenoxycarbonyl)phenyl]propenoyl}amino acetate methansulfonate; 20 mg/kg body wt), but then returned to the preloading value at 12 h after administration. The pancreatic fluid secretion, rich in chloride but poor in bicarbonate, was significantly elevated at 6–12 h postfeeding (100.9 ± 8.2 vs. 27.3 ± 2.3 μl/30 min in control rats, P < 0.01). Loxiglumide (50 mg ⋅ kg body wt−1 ⋅ h−1), atropine (100 μg ⋅ kg body wt−1 ⋅ h−1), or antisecretin serum (100 μl/rat) at 12 h postfeeding did not modify the fluid hypersecretion. Loxiglumide, when given together with PI, completely abolished fluid hypersecretion, but it could not inhibit hypersecretion when applied 3 h after PI treatment. Labeling with 5-bromo-2′-deoxyuridine showed active proliferation of acinar cells at 3 h after PI treatment (3.56 ± 0.29% vs. 0.46 ± 0.08% in control, P < 0.001), but not in rats given loxiglumide together with PI. In rats that fasted from 12 h before to 12 h after PI feeding, neither pancreatic fluid hypersecretion nor active proliferation of acinar cells was observed. These results suggest that pancreatic fluid hypersecretion in fed rats at 6–12 h after PI treatment is caused not by CCK-, secretin-, or cholinergic-dependent mechanisms but probably by acinar cell proliferation.