Biomedical subjects

W Y Chey

Publications and source records attributed to W Y Chey.

At least 55 records · Page 3Linked to original sources

PubMed1997

Effect of cisapride and renzapride on gastrointestinal motility and plasma motilin concentration in dogs.

The effects of cisapride and renzapride (BRL 24924), on plasma concentration of motilin and gastroduodenal motility were studied in seven dogs with implanted force transducers in the antrum and duodenum. In the interdigestive state, the i.v. administration of cisapride (5 mg) or renzapride (5 mg) administered in phase I resulted in a prompt and marked increase in plasma motilin concentration and in gastroduodenal motility. Mean plasma motilin levels during the first 30 min after cisapride and after renzapride injection were 85.0 +/- 6.5 (+/- S.E.) and 96.1 +/- 6.3 pM., respectively. These values were significantly greater (P < .001) than those for the corresponding time period of the control cycle, 52.2 +/- 5.6 and 57.4 +/- 5.3 pM (mean phase III level, 120 +/- 8.1 pM), respectively. The increases in the motilin level after cisapride or renzapride coincided with significant increases in contractile activities of the antrum to 43.2 +/- 5.3% and 44.9 +/- 4.6% and of the duodenum to 28.4 +/- 3.1% and 34.2 +/- 2.2% of phase III activity (100%) from that in the corresponding control period, 0.7 +/- 0.4% and 0.2 +/- 0.1%, respectively. The changes in both plasma motilin and motility in response to the two drugs were abolished completely by the i.v. administration of atropine. The drugs also enhanced the meal-induced contractile activities of the antrum as well as the duodenum but failed to influence the postprandial plasma motilin concentration. We conclude that cisapride and renzapride have similar effects on plasma motilin and gastroduodenal motility: 1) the two drugs increase plasma motilin levels and stimulate gastroduodenal motility in the interdigestive state, and 2) in the digestive state, both drugs enhance motility without influencing the plasma motilin levels.

Animals↗

PubMed1996

Octreotide diminishes luminal nutrient transport activity, which is reversed by epidermal growth factor.

BACKGROUND: Octreotide (SMS) is a somatostatin analogue utilized in patients with short bowel syndrome (SBS) to decrease output. It may inhibit small bowel adaptation by blocking the secretion of trophic hormones such as epidermal growth factor (EGF). This study delineates the effects of SMS and EGF on nutrient transport in SBS. METHODS: One week after 70% jejunoileal resection, 20 New Zealand White rabbits (2 kg) received subcutaneous infusions of saline or EGF (1.5 micrograms/kg/hr) and injections of saline or SMS s.q.b.i.d. The study groups were EGF/saline, saline/saline, saline/SMS, and EGF/SMS. After 7 days of infusion, intestinal brush border membrane vesicles were prepared and nutrient transport measured. RESULTS: SMS reduced active nutrient transport. Kinetics confirmed this was secondary to a reduction in functional carriers in the brush border membrane, without a change in carrier affinity. The coinfusion of EGF ameliorated this effect. On an individual basis, EGF alone did not significantly increase nutrient transport, but when taken as a group, nutrients transport was upregulated 26%. CONCLUSIONS: SMS is detrimental to small bowel adaptation. EGF reverses this effect and may benefit patients with SBS who require SMS to control high intestinal output.

Amino Acids↗

PubMed1996

Effect of transcutaneous nerve stimulation on esophageal function in normal subjects--evidence for a somatovisceral reflex.

Transcutaneous stimulation (TNS) at esophageal acupuncture points decreases lower esophageal sphincter (LES) pressures in patients with achalasia. We examined the effect of TNS on esophageal motility and vasoactive intestinal peptide (VIP) levels in normal subjects. TNS was applied to either hand or foot (placebo) in 10 volunteers. Esophageal and LES pressures were recorded and blood was drawn for VIP analysis. Hand TNS improved LES relaxation and percent of peristaltic contractions to swallows, and decreased the number of spontaneous contractions. Foot TNS decreased only spontaneous contractions while LES pressures and VIP levels were unchanged. We conclude that a somatovisceral pathway involving the esophagus exists.

Acupuncture Points↗

PubMed1996

Adaptation to fat markedly increases pancreatic secretory response to intraduodenal fat in rats.

Exposure to higher levels of fat in the diet increases the secretion of fat-digesting enzymes in pancreatic juice. This study examines the functional consequences of this phenomenon and demonstrates that adapting rats to high fat (triglyceride) loads increases the release of cholecystokinin (CCK) and the pancreatic secretory response to intraduodenal fat. Lipolytic activity in the small intestine was also higher in adapted rats. Exchanging pancreatic juice from unadapted rats with pancreatic juice from adapted rats decreased the response to fat in adapted rats and increased the response to fat in unadapted rats. Infusing oleic acid into unadapted rats stimulated CCK secretion and pancreatic exocrine secretion to levels observed with triglycerides in adapted rats. Pancreatic exocrine secretion in response to intraduodenal fat in rats adapted to a high-fat (20%) diet were significantly higher than the responses seen in rats fed a low-fat (5%) diet. Adaptation to fat increases the pancreatic secretory and plasma CCK responses to fat, apparently by increasing the efficiency of triglyceride digestion and thereby increasing CCK release.

Adaptation, Physiological↗

PubMed1996

Pituitary adenylate cyclase-activating polypeptide stimulates cholecystokinin secretion in STC-1 cells.

Secretion of cholecystokinin (CCK) from the endocrine cells of small intestinal mucosa and the murine intestinal tumor cell line STC-1 is known to involve both adenosine 3',5'-cyclic monophosphate (cAMP)-and Ca(2+)-dependent signal transduction pathways. However, the endogenous stimulant(s) that acts through the cAMP-dependent cascade has not been identified. We determined the effect of pituitary adenylate cyclase-activating polypeptide (PACAP) on CCK secretion and cAMP production and its interaction with other CCK secretagogues in STC-1 cells. At concentrations > 10 nM, PACAP-27 stimulated the release of large intestinal CCK from STC-1 cells in a time- and dose-dependent manner. The stimulatory effect of PACAP-27 was enhanced by the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). PACAP-27, PACAP-38, and vasoactive intestinal polypeptide (VIP), with or without IBMX, were equally effective and potent to elicit CCK release with similar half-maximal doses and maximal levels of stimulation. Both forms of PACAP and VIP stimulated a transient but not significant increase in the cellular cAMP level. In the presence of IBMX, all three peptides increased significantly the cellular cAMP level between 2 and 5 min, but PACAP produced a two times higher level than VIP. The stimulatory effect of PACAP-27 on CCK release was also potentiated by bombesin and KCl but without a synergistic production of cAMP. With or without IBMX, PACAP-27-stimulated CCK secretion was not affected by the Ca2+ channel blocker diltiazem (1 microM), the cell-permeable Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester (BAPTA-AM; 25 microM), or by downregulation of protein kinase C. The stimulatory effects of KCl and bombesin were either reduced or abolished by these treatments. The synergistic effect of bombesin with PACAP was abolished by diltiazem and BAPTA-AM but not by downregulation of protein kinase C, whereas KCl remained synergistic with PACAP after these treatments. Taken together, these results indicate that PACAP may be a neuromodulator of CCK secretion that acts through activation of adenylate cyclase and may function as a coregulator with other CCK secretagogues that are known to increase intracellular Ca2+ concentration.

Animals↗

PubMed1996

Inhibition of acid secretion by electrical acupuncture is mediated via beta-endorphin and somatostatin.

Electroacupuncture (EAP) was shown to inhibit basal gastric acid secretion in dogs and sham feeding-stimulated acid secretion in humans. However, its effect on a meal-stimulated acid secretion in dogs and the mechanisms involved remain unclear. In five dogs prepared with gastric cannulas, gastric acid secretion was determined by a dye-dilution technique for 60 min after intragastric administration of 200 ml of 4% mixed amino acid meal in six different experiments: study 1, no acupuncture; study 2, sham acupuncture (SAP); study 3, EAP; study 4, EAP plus naloxone; study 5, naloxone alone; and study 6, intravenous infusion of somatostatin (SS) and vasoactive intestinal peptide (VIP) at doses of 0.5 and 1.0 micrograms.kg-1.h-1, respectively. EAP was performed on three different points including Pishu, ZusanLi, and Neiguan. Biphasic electrical pulse (25-100 Hz, 12-16 mA) was applied continuously via needles for 75 min starting 15 min before meal. SAP on nonacupoints in hind- and forelegs was performed with the same electrical pulse. Plasma SS, VIP, beta-endorphin, and gastrin were determined by specific radioimmunoassays. EAP significantly inhibited acid secretion (75%; P < 0.01), which coincided with significant increases in plasma SS, VIP, and beta-endorphin and a significant decrease in plasma gastrin. Naloxone completely reversed EAP-induced inhibition of acid secretion and changes in plasma concentration of peptides. SAP also significantly suppressed acid output (30%; P < 0.05), with a modest but significant increase in plasma beta-endorphin. However, the inhibition by EAP on the acid output was significantly greater than that by SAP (P < 0.01). Furthermore, exogenous SS (0.5 microgram.kg-1.h-1) significantly inhibited acid output (78%), whereas VIP failed to inhibit gastric acid secretion. We conclude that, in dogs, EAP significantly inhibits meal-stimulated acid secretion. This acid inhibition is mediated by the release of beta-endorphin and somatostatin, and an endogenous opiate or opiates appear to play an important role in the release of SS, VIP, and beta-endorphin.

Acupuncture Therapy↗

PubMed1995

Galanin inhibits cholecystokinin secretion in STC-1 cells.

Neuropeptides such as gastrin releasing peptide and pituitary adenylate cyclase activating polypeptide (PACAP) stimulate CCK secretion from CCK producing cells. We hypothesized that in addition to somatostatin, galanin may also play an inhibitory role on CCK secretion. The effect of galanin on CCK secretion was studied in a CCK-producing murine neuroendocrine tumor cell line, STC-1. Galanin below 10 nM did not affect basal CCK secretion but dose- and time-dependently inhibited KCl-stimulated CCK secretion. Galanin also inhibited forskolin-, bombesin- and PACAP- but not dibutyryl cAMP- or beta-TPA-stimulated CCK secretion. The inhibitory effect of galanin was reduced partially by a blocker of ATP-sensitive K+ channel (K+ ATP), glibenclamide, and prevented by pretreatment of the cells with PTX. The results indicated galanin regulates CCK secretion by modulation of K+ ATP and cAMP production through receptors coupled to a PTX-sensitive G protein.

Adenylate Cyclase Toxin↗

PubMed1995

The mechanism of inhibitory action of secretin on gastric acid secretion in conscious rats.

1. Secretin has been recognized as an important enterogastrone. In order to investigate the mechanism of secretin-induced inhibition of gastric acid secretion, the effects of both anti-somatostatin antibody and indomethacin on acid secretion were examined in conscious rats with gastric cannulas. 2. Secretin given intravenously at 5.6 pmol kg-1 h-1 inhibited profoundly the acid secretion stimulated by pentagastrin at 0.3 microgram kg-1 h-1. 3. When a rabbit antisomatostatin serum was given intravenously, it not only abolished the secretin-induced inhibition on the pentagastrin-stimulated acid secretion, but also augmented both basal and pentagastrin-stimulated acid secretion. 4. Indomethacin also significantly augmented basal acid secretion, starting 45 min after the drug delivery began. It reversed the secretin-induced inhibition but it did not augment the pentagastrin-stimulated acid secretion. 5. Neither antisomatostatin serum influenced prostaglandin E2-induced inhibition of the pentagastrin-stimulated acid secretion, nor did indomethacin affect the inhibition by somatostatin, suggesting strongly that the inhibition by somatostatin is not mediated by endogenous prostaglandins, nor is that by prostaglandins E2 mediated by endogenous somatostatin. 6. It is concluded that the inhibitory action of secretin on pentagastrin-stimulated gastric acid secretion is mediated by both somatostatin and prostaglandins in conscious rats. The two inhibitors do not seem to interact endogenously for the inhibition of acid secretion. While endogenous somatostatin exerts a tonic inhibitory effect on both basal and pentagastrin-simulated acid secretion, prostaglandins augment basal acid secretion only.

Animals↗

PubMed1995

Acid secretion during indomethacin therapy. Effect of misoprostol.

Secretin is an important physiologic regulator of gastric acid and pancreatic bicarbonate secretion. Endogenous prostaglandins play an important intermediary role, because indomethacin pretreatment prevents the physiological actions of secretin. Misoprostol is a prostaglandin E1 (PGE1) analog used for the prevention of nonsteroidal antiinflammatory drug (NSAID)-induced ulceration. This study sought to determine whether cotherapy with misoprostol reverses the NSAID-induced blockade of secretin's inhibition of human gastric acid secretion. Seven healthy volunteers were studied. Gastric acid secretion was measured during the basal, pentagastin-stimulated and intravenous secretin--inhibited states. The studies were then repeated after 3 days of oral indomethacin (50 mg p.o. t.i.d. for 10 doses) with and without concomitant misoprostol (200 micrograms q.i.d. for 13 doses). Exogenous secretin reduced pentagastrin-stimulated acid secretion by 35%, and this inhibition was reduced to 9% during indomethacin treatment (p < 0.05). Cotherapy with misoprostol during indomethacin treatment did not restore secretin's inhibition of gastric acid secretion; paradoxically, during secretin administration, acid secretion increased. When subjects received misoprostol treatment only, secretin failed to inhibit gastric acid secretion. We conclude that during indomethacin treatment, cotherapy with misoprostol cannot restore the inhibitory action of secretin to inhibit gastric acid secretion. These results suggest that PGE1 is an unlikely intermediate in secretin's physiological action. Although misoprostol can prevent NSAID-induced ulcers, it does not ameliorate all physiological perturbations induced by cyclooxygenase inhibition.

Adult↗

PubMed1995

Aspirin inhibits secretagogue-stimulated and postprandial pancreatic exocrine secretion in conscious rats.

The effect of salicylate and nonsalicylate antiinflammatory drugs and prostaglandins (PGs) on pancreatic exocrine secretion are controversial. We studied the effect of aspirin (ASA) on secretin- and cholecystokinin (CCK)- or meal-stimulated pancreatic secretion. The interrelation between ASA, PG, and pancreatic exocrine secretion was also investigated. Conscious rats with chronic duodenal, pancreatic, and biliary cannulas received secretin (5 pmol/kg/h, i.v.) and CCK (56 pmol/kg/h) or a meal with administration of cimetidine (20 mg/kg/h, i.v.), ASA (1.2, 12, or 60 mumol/h, i.v.), Salicylic acid (SA) (1.2, 12, or 60 mumol/h, i.v.), prostaglandin E2 (PGE2) (10 micrograms/kg/h), or indomethacin (2 mg/kg) was given, respectively. Pancreatic flow volume, bicarbonate, and protein were determined every 15 min. An inhibitor, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) (36 micrograms/kg/h) and an activator, phorbol ester (12-O-tetradecanoyl-phorbol 13-acetate, TPA) (100 ng/kg/h) were used for evaluation of the role of protein kinase C on basal and secretagogue-stimulated pancreatic secretion. ASA, but not SA inhibited the secretin- and CCK-stimulated pancreatic secretion including volume, bicarbonate, and protein in a dose-dependent manner without affecting basal pancreatic secretion. ASA and indomethacin suppressed meal-stimulated pancreatic secretion up to 83.8%. PGE2 significantly inhibited the secretin- and CCK-stimulated pancreatic secretion which was further suppressed by the concomitant ASA infusion. Modulation of protein kinase C failed to affect pancreatic secretion. The data indicate that ASA inhibits both secretin- and CCK-stimulated pancreatic secretion by a mechanism independent of prostaglandin biosynthesis inhibition.

Animals↗

PubMed1995

Negative feedback regulation of pancreatic exocrine secretion in guinea pigs.

We have investigated whether hormonally mediated negative feedback mechanisms regulate pancreatic exocrine secretion in guinea pigs. In anesthetized guinea pigs prepared with a tube in the proximal duodenum, pyloric ligation, and pancreatic duct cannulation with PE-10 tubing, diversion of pancreatic juice for as long as 4 h in fasting states failed to increase either pancreatic secretion or plasma levels of secretin or cholecystokinin (CCK). In the same animal preparation, intraduodenal (ID) infusion of sodium oleate (SO) resulted in significant increases in both pancreatic secretin and plasma levels of the two hormones that were significantly suppressed by ID infusion of pancreatic juice or a combination of trypsin and chymotrypsin. In another group of guinea pigs, this significant increase in pancreatic secretion was profoundly suppressed by a rabbit antisecretin serum (0.2 ml) or loxiglumide (10 mg.kg-1.h-1). Moreover, a combination of the antiserum and loxiglumide completely abolished the pancreatic secretion. The effect of atropine, 20 micrograms.kg-1.h-1 i.v., on SO-stimulated pancreatic secretion and hormone release was also studied. Atropine completely suppressed the pancreatic secretion of volume flow, bicarbonate, and protein stimulated by SO, whereas neither one of the two hormone levels was affected by intravenous atropine, indicating that atropine blocks the actions of both secretin and CCK on the pancreatic exocrine secretion. It is concluded that a negative feedback regulation of exocrine pancreatic secretion is operative in the intestinal phase of pancreatic secretion in guinea pigs and that this feedback mechanism is mediated by both secretin and CCK. Furthermore, in guinea pigs, cholinergic tone plays an important modulating role in the mechanism.

Animals↗

PubMed1995

Effect of endogenous insulin on pancreatic exocrine secretion in perfused dog pancreas.

Canine pancreas was perfused with an intraarterial infusion of Krebs-Ringer bicarbonate solution containing 5% dog red blood cells, 0.1% bovine serum albumin, and 3% dextran at 15 ml/min, while portal effluent was continuously collected. Pancreatic juice was obtained in 15-min samples via main pancreatic duct cannulation. After a 1-h basal period, secretin and cholecystokinin-8 (CCK), at doses of 2.5 ng.min-1 each, were simultaneously infused for 10 min, with background infusion of a normal rabbit serum (NRS) or an antiinsulin serum (Anti-I) in 5 ml each via a sidearm of the intraarterial catheter. The infusion of secretin and CCK resulted in a significant increase in pancreatic bicarbonate and protein secretion during the infusion of NRS, whereas the pancreatic secretory response of bicarbonate and protein was profoundly suppressed by the infusion of Anti-I in six pancreata so studied. This suppression by Anti-I coincided with significant increases in somatostatin and pancreatic polypeptide levels in portal venous effluent. In three additional pancreata, simultaneous infusions of Anti-I with antisomatostatin (5 ml) and antipancreatic polypeptide (5 ml) serum failed to inhibit the pancreatic exocrine secretion. These results indicate that secretin- and CCK-stimulated pancreatic secretion of bicarbonate and protein depends heavily on local action of insulin. The suppression by Anti-I of pancreatic secretion is mediated, in part, by local releases of somatostatin and pancreatic polypeptide. Thus, the insuloacinar axis plays an important regulatory role in pancreatic exocrine secretion in the dog, and it involves at least three islet hormones including insulin, somatostatin, and pancreatic polypeptide.

Animals↗

PubMed1995

Neuronal regulation of the release and action of secretin-releasing peptide and secretin.

The acid-stimulated release of secretin is mediated by a secretin-releasing peptide (SRP) in rats. In the present study we investigated to determine whether a neural mechanism(s) is involved in the regulation of release and action of SRP in anesthetized rats. A concentrated acid perfusate (CAP) containing SRP was obtained from donor rats. CAP administered to recipient rats significantly increased pancreatic flow volume (81.6 +/- 18.3%), bicarbonate output (188.7 +/- 15.6%), and plasma secretin level (from 0.9 +/- 0.2 to 4.4 +/- 0.5 pM). However, this effect was attenuated by CAP from donor rats pretreated with tetrodotoxin (TTX), propranolol, bilateral subdiaphragmatic vagotomy (BSV), or systemic and topical administration of capsaicin. In contrast, CAP from donor rats pretreated with phentolamine, atropine, or hexamethonium did not alter the increase in plasma secretin concentration and pancreatic secretion. Moreover, the action of CAP on secretin release was significantly inhibited in the recipient rats pretreated with TTX, BSV, and topical applications of capsaicin but was not suppressed in the recipient rats pretreated with atropine, hexamethonium, or propranolol. Furthermore, perivagal and duodenojejunal mucosal application of capsaicin abolished the pancreatic secretory response to secretin at 5 pmol.kg-1.h-1. In conclusion, the release and action of both SRP and secretin are mediated by a vagal afferent pathway. beta-Adrenergic receptors also play a significant role in the release of SRP.

Acids↗

PubMed1995

Modulation of gallbladder contraction by pirenzepine in humans.

OBJECTIVES: The mechanism(s) by which cholinergic innervation modulates gallbladder contraction are not fully understood. To elucidate the role of muscarinic M1 receptors in the mediation of gallbladder contraction, we investigated gallbladder volume reduction, plasma cholecystokinin (CCK), and pancreatic polypeptide (PP) responses in humans during cephalic and intestinal phases of a meal under M1 muscarinic receptor blockade with pirenzepine. METHODS: In eight healthy subjects, intraduodenal meal- and in seven subjects, sham feeding-induced gallbladder volume reduction was measured by real-time ultrasonography during saline or pirenzepine administration. Plasma CCK and PP were measured by radioimmunoassay. RESULTS: Pirenzepine partially inhibited gallbladder volume reduction in response to an intraduodenal fatty meal. The integrated gallbladder volume reduction over 120 min was 4462 +/- 445%.min compared with 6879 +/- 279%.min in the saline control group (p < 0.01). Integrated plasma CCK and PP responses were unchanged in the presence of pirenzepine. Pirenzepine abolished sham feeding-induced gallbladder contraction and plasma PP response. Sham feeding with either isotonic saline or pirenzepine infusion did not modify fasting plasma CCK levels. CONCLUSION: M1 muscarinic receptors play an important role in the intestinal and cephalic phases of gallbladder contraction. Plasma CCK response to intraduodenal meal is not influenced by M1 muscarinic receptor blockade with pirenzepine.

Adult↗

PubMed1995

The cause of death in inflammatory bowel disease: a comparison of death certificates and hospital charts in Rochester, New York.

OBJECTIVE: This study examines the causes of death from Crohn's disease and ulcerative colitis by comparing death certificates with hospital charts as part of an ongoing, community-based analysis in Rochester, NY. METHODS: A registry of 1358 inflammatory bowel disease patients followed from January 1973 to December 1989 was analyzed for the cause of death by a study of death certificates as well as by a study of hospital records, including surgical pathology and autopsy records. A panel of physicians defined specific criteria for diagnosis, cause of death, and relation of death to inflammatory bowel disease. RESULTS: One hundred and thirty patients (59 with ulcerative colitis and 71 with Crohn's disease) from the registry were found to have death certificates recorded by Monroe County during this period. There was an 80% concordance of the death certificate to the hospital record for the cause of death and its relationship to inflammatory bowel disease. Discordance was noted in cases of colon cancer and surgical complications. CONCLUSIONS: Sixty-eight percent of Crohn's disease and 78% of ulcerative colitis patients died from causes unrelated to their inflammatory bowel disease. Deaths caused by Crohn's disease decreased from 44% in the 1973-1980 period to 6% in the 1981-1989 period. Crohn's disease was a direct cause of death in 25% of the female patients, whereas only 6% of male patients died directly of Crohn's disease. Colorectal cancer caused 14% of the deaths in ulcerative colitis patients, three times more often than in Crohn's disease patients. Excluding cancer, there were only two deaths directly due to ulcerative colitis, both in the first 2 yr after diagnosis.

Adolescent↗

PubMed1994

Characterization of the release of cholecystokinin from a murine neuroendocrine tumor cell line, STC-1.

The murine neuroendocrine cell line, STC-1, was found to contain 296.8 +/- 1.8 fmol of cholecystokinin-like immunoreactivity (CCK-LI) per mg cell protein. Immunocytochemical stain of STC-1 cells maintained in monolayer culture indicated that CCK-LI activity was present in 93% of the cells. Analysis by reverse-phase high-performance liquid chromatography indicated that STC-1 cells contained CCK-8 and an unidentified form as the predominant storage form. form. However, only CCK-8 was released into the culture medium upon stimulation by various secretagogues. The release of CCK-LI from STC-1 cells was stimulated by dibutyryl cAMP, forskolin, KCl, A23187, 4 beta-phorbol 12-myristate 13-acetate and luminal stimulants, e.g., sodium oleate, L-tryptophan, camostat and plaunotol. The release of CCK-LI from STC-1 cells was also stimulated by a neuropeptide, bombesin. The stimulatory effects of most of these agents were dose dependent. The stimulatory effects of dibutyryl cAMP, forskolin, and plaunotol were potentiated by 3-isobutyl-1-methyl xanthine, while that of camostat was not. The results obtained in this study indicate that the release of CCK from STC-1 cells shares the same characteristics of CCK release as from the CCK-secreting cells of the intestinal mucosa observed both in the dog and the rat in vitro and in vivo. Thus, the cellular mechanism of CCK release which appears to be cAMP- and Ca(2+)-dependent may be modulated by cellular protein kinase C activity. The STC-1 cell appears to be a suitable model for studying the mechanism of CCK release.

Animals↗

PubMed1994

Physiological role of cholecystokinin on gastric emptying and acid output in dogs.

We investigated the physiological role of cholecystokinin (CCK) on gastric emptying and acid secretion in seven conscious dogs with gastric cannulae. Two hundred milliliters of a 4% amino acid meal was given via the cannula, and both gastric emptying and acid output were measured concurrently using a dye-dilution technique. Gastric emptying of the liquid amino acid meal was exponential, and the acid output and plasma concentrations of CCK, gastrin, and somatostatin peaked within 30 min after the meal. Intravenous infusion of CCK-8 at 28 and 56 pmol/kg/hr but not 14 pmol/kg/hr increased plasma levels of the peptide and inhibited gastric emptying as well as acid output. Plasma gastrin was not affected significantly by the CCK infusion, whereas plasma somatostatin increased significantly in response to 56 pmol/kg/hr of CCK-8. Loxiglumide, 22 mumol/kg/hr, significantly enhanced gastric emptying and augmented acid output, as well as plasma gastrin response, whereas it abolished the postprandial rise in plasma somatostatin. We concluded that in dogs, CCK plays an important role in the physiologic regulation of postprandial gastric emptying of a liquid caloric meal and acid output. Its inhibitory effect on gastric acid secretion appears to be mediated, at least in part, by somatostatin.

Animals↗

PubMed1994

CCK-receptor antagonists proglumide and loxiglumide stimulate bile flow and biliary glutathione excretion.

The mechanism for the choleresis induced by CCK-receptor antagonists, proglumide, loxiglumide, and CR 1409, was examined in anesthetized rats and compared to the effects of CCK itself. These agents were infused intravenously over a 2-hr period, and bile flow, and biliary excretion of bicarbonate, total bile acids, and glutathione were measured in 30-min intervals. All three antagonists produced a dose-dependent choleresis, but a significant decrease in bile acid excretion, indicating that they stimulate bile flow via a bile acid-independent mechanism. The increase in bile flow was associated with a parallel increase in biliary glutathione and bicarbonate output in rats treated with proglumide and loxiglumide. In animals pretreated with acivicin to inhibit gamma-glutamyltransferase activity, proglumide was shown to stimulate biliary excretion of reduced glutathione (GSH), but not glutathione disulfide (GSSG), indicating the absence of oxidative stress in the liver. GSH output was increased by only 0.5-0.9 mumol/30 min after infusion of proglumide at a dose of 75 mg/kg/hr, whereas bile volume was increased 0.2-0.4 ml/30 min, indicating that this increased biliary GSH excretion can account for only a small fraction of the increased bile volume, given an osmotic efficiency for GSH of 34 microliters/mumol. In contrast to CCK receptor antagonists, CCK itself had no effect on bile flow and outputs of bicarbonate, GSH, and bile acids, suggesting that the effects of the antagonists are not related to their interaction with CCK receptors. These findings demonstrate that proglumide and loxiglumide stimulate a bile acid-independent bile flow that is only partially explained by an increase in GSH excretion.

Animals↗