sincalide and osteum

Duodenal fat such as oleate is known to influence gut functions by release of cholecystokinin (CCK), but the contribution of CCK endogenously released by duodenal fat or by diversion of pancreatic juice from the duodenum in the mechanism of mucosal integrity and gastroprotection has been little studied. This study was designed to compare the effect of CCK-8 and intraduodenal (i.d.) instillation of sodium oleate, or diversion of the pancreatic biliary secretions that are known to release CCK, on the gastric mucosal lesions induced by topical application of 100% ethanol or acidified aspirin (ASA) in rats with or without the pretreatment with a CCK-A receptor antagonist, loxiglumide, or with L-365,260 to block CCK-B receptors. In addition, the effect of suppression of prostaglandin (PG) biosynthesis by indomethacin (5 mg/kg i.p.), inhibition of nitric oxide (NO)-synthase by L-NAME (5 mg/kg i.v.), or blockade of sensory nerves by capsaicin (125 mg/kg s.c.) on the protective activity of sodium oleate was determined. Sodium oleate (50-200 mM i.d.), or diversion of pancreatic juice from the duodenum for 3 h that produced significant rise in plasma CCK levels, significantly reduced gastric lesions induced by 100% ethanol to an extent similar to that induced by exogenous CCK-8 (5 nmol/kg s.c.). The protective effect of oleate or diversion of pancreatic juice was accompanied by an increase in gastric blood flow (GBF). Both protection and accompanying hyperemia were completely abolished by blockade of CCK-A receptors with loxiglumide, whereas L-365,260, an antagonist of CCK-B receptors, had no effect. Oleate given i.d. significantly attenuated acidified ASA-induced gastric lesions and gastric secretion while increasing the luminal concentration of somatostatin. These effects were significantly reduced by loxiglumide but not by L-365,260. In contrast, CCK-8, which stimulated gastric acid secretion, failed to affect the lesions induced by acidified ASA and the decrease in the GBF produced by this ulcerogen. Indomethacin, which suppressed PG generation by approximately 90%, failed to influence the protective activity of oleate or CCK-8 against ethanol-induced lesions, whereas L-NAME, vagotomy, or sensory denervation significantly attenuated this protection and accompanying hyperemia. Addition to L-NAME of L-arginine, but not D-arginine, restored the protective and hyperemic effects of CCK-8 and duodenal oleate against gastric lesions induced by ethanol or acidified ASA

Topics: Animals; Capsaicin; Cholecystokinin; Denervation; Dinoprostone; Dopamine Agents; Enzyme Inhibitors; Gastric Acid; Gastric Mucosa; Hormone Antagonists; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Oleic Acid; Pepsin A; Proglumide; Rats; Rats, Wistar; Receptor, Cholecystokinin A; Receptors, Cholecystokinin; Sincalide; Somatostatin; Stomach Ulcer; Vagotomy

In the present investigation, we have studied the effect of atropine on the pancreatic secretion stimulated by intraduodenal administration of either sodium oleate or exogenous cholecystokinin (CCK). In four dogs prepared with gastric and Thomas duodenal cannulas, pancreatic juice was collected for measurement of volume, bicarbonate, and protein output, and peripheral venous blood samples were obtained for radioimmunoassay of both secretin and CCK. Volume, bicarbonate, and protein output of the pancreatic juice increased significantly in response to sodium oleate (1-4 mmol/h) in a dose-dependent manner. The increase in pancreatic secretion paralleled the increments in both plasma CCK and secretin. Atropine given intravenously suppressed completely both pancreatic secretion and release of CCK stimulated by sodium oleate, whereas the release of secretin was not affected. Pancreatic secretion was significantly increased in a dose-dependent manner by exogenous CCK octapeptide (CCK-8) at 16, 32, and 64 micrograms (14, 28, and 56 pmol).kg-1.h-1. Atropine inhibited protein output only partially, but it did not influence bicarbonate output. In five additional dogs, the effect of atropine on L-tryptophan-stimulated pancreatic secretion was studied. Interestingly, atropine failed to influence the CCK release and pancreatic secretion of volume and bicarbonate, except for protein secretion, which was significantly inhibited. It was shown previously that atropine inhibited significantly the pancreatic secretion of bicarbonate stimulated by secretin in physiological doses. Thus we conclude that the inhibition by atropine of the pancreatic exocrine secretion stimulated by sodium oleate is mediated by both suppression of CCK release and inhibition of action of secretin on the exocrine pancreas.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Atropine; Cholecystokinin; Dogs; Dose-Response Relationship, Drug; Oleic Acid; Oleic Acids; Pancreas; Secretin; Sincalide; Tryptophan

The ability of intraintestinal nutrient infusions to suppress sham feeding was examined in intact rats and in rats with total subdiaphragmatic vagal transections. Vagotomy abolished the suppression of sham feeding by intraintestinal infusion of maltose or oleate. Suppression of sham feeding by intraintestinal L-phenylalanine was reduced but not abolished by vagotomy. The results of this examination indicate that the vagus nerve mediates suppression of the sham feeding by intraintestinal maltose and oleate but is only partially responsible for suppression of food intake produced by L-phenylalanine. Taken together with previously published data these results suggest that effects on feeding by specific nutrients may be mediated by anatomically distinct populations of visceral afferent neurons.

Topics: Animal Nutritional Physiological Phenomena; Animals; Cholecystokinin; Eating; Injections; Intestinal Mucosa; Intestines; Male; Maltose; Oleic Acid; Oleic Acids; Phenylalanine; Rats; Rats, Inbred Strains; Sincalide; Sucrose; Vagotomy

Amylase secretion and plasma cholecystokinin (CCK) were measured in dogs in the interdigestive state and after exogenous CCK-8 and CCK-39 (12.5 to 400 pmol.kg-1.h-1), intestinal sodium oleate, tryptophan plus phenylalanine, HCl (0.74, 2.2, 6.7, 20 mmol/h), and a meat meal (20 g/kg). Interdigestive plasma CCK did not vary, although amylase output showed periodic 15-fold increases. Plasma CCK increased linearly after doubling doses of CCK-8 and CCK-39; the slope of plasma CCK-39 vs. dose was 2.8 times steeper than that of CCK-8, suggesting a longer circulating half-life. At similar plasma concentrations, CCK-8 and CCK-39 were equipotent for stimulating pancreatic secretion. Sodium oleate and tryptophan plus phenylalanine significantly increased plasma CCK and amylase secretion in a load-dependent pattern and were equipotent for both effects. HCl stimulated bicarbonate secretion but not plasma CCK or amylase secretion. Food significantly increased plasma CCK and amylase secretion. Amylase responses to intestinal stimulants and food were significantly greater than to exogenous CCK at low plasma CCK levels. Maximal amylase responses to intestinal stimulants were similar to that after CCK-39 but occurred at 10-fold lower plasma CCK levels. These results indicate that CCK and other factors interact to regulate pancreatic responses to food and intestinal stimulants in dogs.

Topics: Amylases; Animals; Cholecystokinin; Dogs; Eating; Injections, Intravenous; Intestines; Oleic Acid; Oleic Acids; Pancreas; Phenylalanine; Sincalide; Tryptophan

We have previously described a cholecysto-sphincter of Oddi reflex whereby sphincter of Oddi (SO) motility is mediated in part by the degree of gallbladder distension. Therefore, we tested the hypothesis that cholecystectomy alters the response of the SO to endogenous and exogenous hormonal stimulation. Eight months after sham laparotomy (n = 8) or cholecystectomy (n = 10), prairie dogs were anesthetized with alpha-chloralose. The common bile duct was cannulated distally with a side-hole, pressure-monitored catheter perfused with degassed water at 0.15 ml/min. The duodenum was cannulated distal to the SO to allow perfusion of the proximal 30 cm of intestine with 20 mmol/L sodium oleate at 0.4 ml/min. In animals undergoing sham laparotomy the gallbladder was cannulated, aspirated, and kept empty throughout the experiment. SO phasic wave frequency (F), amplitude (A), and baseline pressure were measured for 60 minutes before and during intraduodenal (ID) perfusion of sodium oleate and then for 60 minutes before and 30 minutes during intravenous (IV) infusion of cholecystokinin-octapeptide (CCK-OP) at 10 ng/kg/min. A SO motility index (MI) (MI = F X A) was calculated for each 10-minute period. Common duct diameter and resting SO motility were unaltered 8 months after cholecystectomy. In animals that had sham laparotomy ID infusion of sodium oleate reduced SO MI by 46% (p = 0.06) and 75% (p less than 0.05) at 30 and 60 minutes, respectively, whereas in animals that had cholecystectomy the reduction in SO MI was only 6% and 25% (p less than 0.05) during the same periods. In animals that had sham laparotomy IV CCK-OP increased the SO MI by 175% (p less than 0.05), but in the animals that had cholecystectomy IV CCK-OP increased SO MI by only 60% (no significance). These findings indicate that after cholecystectomy resting SO motility is unaltered, but the response to ID sodium oleate and to IV cholecystokinin is blunted. We suggest that cholecystectomy alters neural pathways that mediate the normal response of the SO to endogenous and exogenous hormonal stimulation.

Topics: Ampulla of Vater; Animals; Cholecystectomy; Gastrointestinal Motility; Male; Neural Pathways; Oleic Acid; Oleic Acids; Pressure; Sciuridae; Sincalide; Sphincter of Oddi

Several secretagogues of exocrine pancreatic secretion have been proposed to act as regulators of pancreatic D-cell function. To characterize this relationship, we measured incremental responses of protein, bicarbonate, and circulating somatostatin to graded doses of intravenous cholecystokinin (CCK-33), CCK-8, caerulein, bombesin, secretin, and intraduodenally perfused HCl, sodium oleate, and L-phenylalanine in conscious dogs with gastric and pancreatic fistulas and compared them with postprandial values (to a beef meal). Bombesin produced dose-related increases in somatostatin secretion (maximal, 46% of meal response), but caerulein, CCK-33, and CCK-8 released only small amounts of somatostatin at doses equivalent for pancreatic protein secretion. Secretin did not stimulate somatostatin release at any dose studied, whereas intraduodenal HCl at a load submaximal for pancreatic bicarbonate secretion increased somatostatin levels slightly (maximal, 16% of meal response). L-Phenylalanine and sodium oleate markedly increased protein secretion, but only oleate clearly stimulated somatostatin release (maximal, 11% of meal response). Our results suggest a greater quantitative importance of the intestinal phase for exocrine pancreatic stimulation than for somatostatin release.

Topics: Animals; Bombesin; Ceruletide; Cholecystokinin; Dogs; Gastric Acid; Oleic Acid; Oleic Acids; Pancreas; Phenylalanine; Secretin; Sincalide; Somatostatin

Cholinergic receptors for cholecystokinin (CCK) have been identified on neurons of the enteric nervous system, including those of the gallbladder. To determine whether any differences exist in the extent to which CCK action depends on muscarinic cholinergic receptors in the pancreas and gallbladder, 11 dogs with pancreatic and 7 dogs with biliary fistulas were given increasing doses of intravenous CCK-8 (15-250 ng X kg-1 X h-1) or intraduodenal sodium oleate (0.1-9 mmol/h) with and without atropine pretreatment. Pancreatic protein response to CCK-8 was dose dependent, reaching a maximal of 448 +/- 76 mg/15 min at the highest dose. Atropine pretreatment caused nonsignificant reduction in the response to the lowest dose but had no effect on the responses to the other doses, with the response to the highest dose of CCK being 473 +/- 82 mg/15 min. In contrast, gallbladder contraction as measured by bile fistula bilirubin output was very sensitive to inhibition by atropine. Bilirubin responses to 16, 32, 62.5, 125, and 250 ng X kg-1 X h-1 were 14 +/- 5, 18 +/- 5, 28 +/- 5, 36 +/- 6, and 52 +/- 12 mg/h, respectively, without atropine and 0 +/- 0, 6 +/- 2, 7 +/- 2, 18 +/- 4, and 18 +/- 4 mg/h with atropine pretreatment. Similarly, pancreatic responses to sodium oleate infusion were less susceptible to inhibition by atropine than were the gallbladder responses. With respect to pancreatic protein secretion, the response to only the lowest dose of sodium oleate was significantly inhibited by atropine.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Atropine; Bile; Bilirubin; Dogs; Gallbladder; Oleic Acid; Oleic Acids; Pancreas; Proteins; Receptors, Cholinergic; Sincalide

The doses of cholecystokinin (CCK) that have been shown to cause satiety after peripheral administration are pharmacological and whether "physiological" doses of exogenous CCK or endogenously released CCK have a satiety effect is not known. The purpose of the present study is threefold: to compare the potency of endogenous and exogenous CCK for their satiety, cholecystokinetic, and pancreozyminic actions; to determine whether small doses of CCK in the presence of gastric distension cause satiety; and to test the satiety effect of CCK administered centrally into the lateral cerebral ventricle. Dogs were prepared with cerebroventricular guides and esophageal and duodenal fistulas (n = 4), with chronic bile fistulas (n = 8), and chronic pancreatic fistulas (n = 7). Satiety effect was quantified in the esophageal fistula dog by the amount of blenderized food sham fed within 7.5 min. Duodenal perfusion of fat, used as a releaser of endogenous CCK, stimulated pancreatic protein, and gallbladder contraction with D50 values of 1.5 and 0.3 mmol/h, respectively, but had no effect on the volume sham fed (316 +/- 82 ml/min without and 371 +/- 41 ml/min with the maximal dose of sodium oleate infused). The D50 values of CCK-8 (pmol X kg-1 X h-1) for satiety and for stimulation of pancreatic enzyme secretion and gallbladder contraction were 440, 120, and 22, respectively. Injection of CCK-8 into the lateral cerebral ventricle inhibited sham feeding in a dose-dependent manner. We conclude that duodenal fat in doses producing maximal gallbladder and pancreatic stimulation has no satiety effect in the dog.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Bilirubin; Dogs; Dose-Response Relationship, Drug; Eating; Gallbladder; Haplorhini; Humans; Mice; Oleic Acid; Oleic Acids; Pancreas; Rabbits; Rats; Satiation; Sheep; Sincalide; Stomach

Truncal vagotomy results in diminished pancreatic protein secretion in response to intraduodenal fat. This diminished secretion may be due, at least in part, to interruption of the vagal reflexes between the intestine and the pancreas that work independently of cholecystokinin (CCK). In five dogs with chronic pancreatic fistulas, plasma CCK concentrations and pancreatic protein secretion in response to an intestinal stimulant (intraduodenal oleate) and to two exogenous peptides (bombesin and CCK-33) were compared before and after bilateral truncal vagotomy. Vagotomy decreased integrated protein secretion by about 50% in response to intraduodenal oleate. In contrast, protein output in response to parenteral stimuli increased after vagotomy. Integrated output of CCK in response to intraduodenal oleate or to exogenous bombesin or CCK was not significantly affected by vagotomy, but release of pancreatic polypeptide was decreased significantly in response to all stimuli after truncal vagotomy. These data provide evidence that truncal vagotomy decreases pancreatic protein secretion in response to intestinal stimulants by interrupting enteropancreatic reflexes mediated by the vagus, while maintaining normal (or supranormal) sensitivity of the pancreas to endogenous and exogenous CCK.

Topics: Animals; Bombesin; Cholecystokinin; Dogs; Duodenum; Female; Male; Oleic Acid; Oleic Acids; Pancreas; Pancreatic Fistula; Pancreatic Polypeptide; Peptide Fragments; Proteins; Reflex; Sincalide; Stimulation, Chemical; Vagotomy; Vagus Nerve

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.

Topics: Animals; Bethanechol; Bethanechol Compounds; Ceruletide; Cholecystokinin; Dogs; Food; Hydrochloric Acid; Oleic Acid; Oleic Acids; Pancreas; Pancreatic Polypeptide; Phenylalanine; Secretin; Sincalide

The effect of atropine and truncal vagotomy on the latency of the secretory response of the exocrine pancreas to rapid intraduodenal injection of L-tryptophan, sodium oleate and HCl or to rapid intraportal injection of secretin or CCK octapeptide has been determined in conscious dogs with pancreatic fistulae. The intraduodenal stimulants were injected either alone or in the presence of an intravenous infusion of secretin, CCK octapeptide or a combination of both hormones. The mean latency of response to tryptophan alone (62 +/- 2 s), oleate alone (64 +/- 5 s) and HCl alone (91 +/- 3 s) was significantly longer (P less than 0.05) than the latency to intraportal secretin (28 +/- 5 s) or CCK octapeptide (45 +/- 4 s). Infusion of secretin alone or with CCK octapeptide significantly shortened the latency of response to tryptophan (38 +/- 3 s) and oleate (41 +/- 5 s), but had no effect on the latency to intraduodenal HCl (96 +/- 4 s). Atropine and truncal vagotomy both increased the latency to intraduodenal tryptophan and oleate threefold but did not affect the latency to intraduodenal HCl or intraportal secretin or CCK octapeptide. These data support the hypothesis that the stimulus to pancreatic fluid secretion evoked by intraduodenal HCl is humoral rather than neural, while the responses to intraduodenal tryptophan and oleate are mediated, at least in part, via an enteropancreatic, vago-vagal, cholinergic reflex.

Topics: Animals; Atropine; Bicarbonates; Cholecystokinin; Dogs; Duodenum; Female; Hydrochloric Acid; Male; Oleic Acid; Oleic Acids; Pancreas; Peptide Fragments; Secretin; Secretory Rate; Sincalide; Tryptophan; Vagotomy