Chronic Gastric Cannulas Research Articles

Prior pregastric food stimulation and gastrin-releasing peptide 1–27 (GRP) synergize to inhibit sham feeding

The hypothesis that prior pregastric food stimulation is sufficient to reveal an inhibitory effect of gastrin-releasing peptide 1–27 (GRP) on sham feeding was tested in 11 male rats equipped with chronic gastric cannulas. Rats were sham fed a high-carbohydrate solution during a 45-min test session, after 17-h food deprivation. GRP (16 or 32 μg/kg) or saline was injected intraperitoneally either at the onset or 5 or 15 min after the onset of sham feeding. This allowed for a 0-, 5-, or 15-min period of pregastric food stimulation before GRP or saline injections. Sham intake was recorded every 5 min, and behavior was observed every minute. GRP inhibited sham feeding when it was administered after 5 or 15 min of prior pregastric food stimulation, but not when it was administered at test onset. A nonsignificant increase in resting behavior and decrease in feeding behavior were associated with the decrease in sham feeding. No anomalous behaviors were noted. We conclude that a synergy between GRP and prior pregastric, presumably oral, food stimulation is sufficient to inhibit sham feeding.

Behaviorally specific inhibition of sham feeding by amylin

To further characterize amylin’s inhibitory action on feeding, we examined the effects of intraperitoneal injections of amylin on sham feeding of sucrose in food-deprived male rats with chronic gastric cannulas. Thirty and 100 μg/kg amylin reduced sham feeding, but did not terminate it or elicit the behavioral sequence of satiety. Real feeding of sucrose, but not sham feeding, was reduced after injection of 10 μg/kg amylin. Amylin’s inhibitory effect on sham feeding appeared behaviorally specific because neither 30 nor 100 μg/kg amylin affected sham drinking of water in thirsty rats and because no abnormal behaviors occurred. We conclude that amylin has a behaviorally specific satiating effect on sucrose sham feeding that is insufficient to elicit satiety in absence of gastric or postgastric food stimulation.

Endogenous cholecystokinin in the control of gastric emptying of liquid nutrient loads in rhesus monkeys

A role for the brain/gut peptide cholecystokinin (CCK) in the control of gastric emptying has been proposed. In the present studies, we have used a potent type A CCK-receptor antagonist (devazepide) to examine the quantitative contribution of endogenously released CCK in the control of liquid gastric emptying of 100 ml lipid, protein, and carbohydrate test loads in rhesus monkeys. Emptying was studied in conscious monkeys equipped with chronic indwelling gastric cannulas. Prior intragastric administration of devazepide (1.0-320 micrograms/kg) differentially affected the 10-min emptying of glucose (0.125/ml), peptone (4.5%), and Intralipid (4.5%). Glucose emptying was not affected by any dose of the CCK antagonist. The emptying of peptone was accelerated by doses of 10 micrograms/kg or higher. This effect, however, was only partial and plateaued at a dose of 100 micrograms/kg. The gastric emptying of Intralipid was accelerated at a dose of 32 micrograms/kg, and the inhibitory effect of the Intralipid was completely eliminated at a dose of 320 micrograms/kg. At this dose of devazepide, the Intralipid test meal emptied from the stomach at the same rate as physiological saline. These data demonstrate that in rhesus monkeys endogenously released CCK 1) does not play a role in the control of glucose emptying, 2) is a partial mediator of the inhibitory action of peptone on gastric emptying, and 3) is the primary inhibitory mediator in the control of the gastric emptying of Intralipid.

Effects of the Ca 2+ chelators EGTA and EDTA on ethanol- or stress-induced gastric mucosal lesions and gastric secretion

Ca 2+ modulates gastric function and dysfunction as well as the release of cysteine proteases and metalloproteinases which have been implicated in the pathogenesis of gastric mucosal lesions. We thus tested the hypothesis that pretreatment with the Ca 2+ chelators, ethylene diamine tetraacetic acid (EDTA) and ethylene glycol-bis(β-aminoethyl ether)-N,N,N′, N′ -tetraacetic acid (EGTA) might reduce the experimental gastric mucosal damage induced by restraint cold stress or 1.0 ml of 75% ethanol. Other rats were prepared with chronic indwelling gastric cannulas and the effects of EDTA and EGTA on conscious basal gastric acid output were assessed. In addition, rats were pretreated with EGTA and EDTA prior to pylorus ligation and their effects on acid and pepsin output assessed. Both EDTA and EGTA reduced significantly the extent of ethanol-induced gastric mucosal damage as well as the degree of stress-induced gastric lesions. To further characterize the mechanism of Ca 2+ chelator protection against ethanol-induced gastric lesions, some rats were vagotomized or adrenalectomized prior to treatment with EGTA or EDTA, followed by ethanol or stress. Both adrenalectomy and vagotomy abolished gastroprotection by EGTA and slightly reduced that induced by EDTA in both models of experimental gastric mucosal injury. Both EDTA and EGTA reduced significantly basal gastric acid output, an effect which persisted for at least 2 h following their administration. Both compounds also decreased significantly acid and pepsin output in pylorus-ligated rats. We conclude that Ca 2+ chelators attenuate both acid-dependent and acid-independent gastric lesions. The effects of EGTA and EDTA likely involve, at least in part, vagal and glucocorticoid/catecholamine mediation, since vagotomy and adrenalectomy completely blocked and reduced, respectively, their protective influence on the gut.

Duration of antisecretory effects of oral omeprazole in horses with chronic gastric cannulae

SummaryEight female horses with chronic gastric cannulae were given omeprazole as enteric‐coated granules (1.4 mg/kg bwt) via nasogastric tube once daily for 6 days. The effects on basal and pentagastrin‐stimulated gastric acid secretion were determined 5 h after dosing on Days 1 and 5 ofadministration. A third gastric secretion test was done on Day 7, 24 h after the dose on Day 6. Gastric juice volume, pH, acidity, and acid output were determined during a 1‐h basal secretion test followed by a 2‐h pentagastrin‐stimulated (6 μg kg−1 h−1) test.When compared with placebo controls, omeprazole significantly inhibited basal gastric acid output by 72% and pentagastrin‐stimulated acid output by 86% on Day 5. Gastric juice pH was also significantly increased. On Day 7, basal gastric acid output was significantly decreased by 90% and pentagastrin‐stimulated secretion was decreased by 72%. The effect of omeprazole administration on gastric juice volume was variable.Once daily administration of 1.4 mg omeprazole/kg bwt significantly inhibited basal and stimulated gastric acid secretion in horses by the 5th dose. Gastric acid secretion was significantly inhibited for at least 27 h after omeprazole treatment, indicating a long duration of antisecretory effect of the drug in horses.

Pharmacokinetics and antisecretory effects of intravenous omeprazole in horses

SummaryEight young female horses with chronic gastric cannulae received 0.5 mg omeprazole/kg bwt iv once daily for 5 consecutive days. Gastric secretion was measured on the 1st and 5th day. Basal secretion was determined 1 h before and 1 h after the omeprazole dose, followed by pentagastrin stimulation for 2 h. Gastric juice samples were collected from the cannula every 15 mins for the determination of volume, pH, acidity, and acid outputs. As control, sterile water was similarly administered to all 8 horses. Pharmacokinetic evaluation of intravenous omeprazole was determined concurrently on the 1st and 5th day of administration.Omeprazole reduced both basal and stimulated acid output (mmol H+/h) by more than 90%, with a significant increase in gastric juice pH both on the 1st and 5th day of administration. A trend suggesting a long duration of inhibitory action was observed 23 h after the 4th dose of omeprazole since 58% of gastric acid output was inhibited. Thus omeprazole shows potential as a once a day antisecretory drug in horses.Plasma omeprazole concentration versus time profiles were best described using a two‐compartment model. There was no statistical difference between the pharmacokinetic disposition of omeprazole on Days 1 and 5. The elimination half‐life of intravenous omeprazole was about 30 mins.

Effect of oral omeprazole on basal and pentagastrin‐stimulated gastric secretion in young female horses

SummaryOmeprazole (0.7 mg/kg bwt), as enteric‐coated pellets in capsules, was administered to 8 horses with chronic gastric cannulae to determine its effect on gastric juice acidity, acid output, pH, and volume. Omeprazole was given via nasogastric tube once daily for 5 days and gastric secretion tests were done on the 1st and 5th day of dosing. Gastric juice samples were collected every 15 mins from the cannula, starting 5 h after the administration of omeprazole. Basal secretion was determined in the first hour of collection followed by a 2‐h determination of pentagastrin (6 μg/kg/h)‐stimulated secretion. Lactose placebo studies were carried out in the same horses for comparison.Basal and stimulated gastric acid output were inhibited by 69% and 76%, respectively, by the 5th day of dosing, when compared with control values. Basal gastric juice pH increased from 3.2 in placebo‐treated horses to 4.6 by the 5th day of omeprazole treatment. Stimulated gastric juice pH was similarly increased from 1.7 to 4.6 by the 5th day of treatment.Omeprazole (0.7 mg/kg bwt) given orally once daily significantly inhibited basal and stimulated gastric acid secretion in horses by the 5th day of administration.

Peptide YY inhibits gastric acid secretion stimulated by the autonomic nervous system.

Peptide YY (PYY), a new peptide found primarily in mucosal endocrine cells of the terminal ileum and colon, inhibits pentagastrin-stimulated gastric acid secretion in several species, including man. Several studies indicate that PYY can affect autonomic neurotransmission, and we have recently shown that PYY can inhibit neurally stimulated release of insulin. The purpose of the present study was to examine the effect of PYY on gastric acid secretion stimulated by the autonomic nervous system. On separate days, 6 dogs that were prepared with chronic gastric cannulas were given 2-deoxy-D-glucose (2-DG; 90 mg/kg, i.v.) for 6 min, either alone, or in combination with PYY (100, 200, or 400 pmol.kg-1.h-1, i.v.) for 60 min. The effect of PYY, at 400 pmol.kg-1.h-1, on gastric acid secretion stimulated by either 2-DG or PG (1 micrograms.kg-1.h-1, i.v.) was studied after treatment with propranolol (0.5 mg/kg, i.v. bolus) or phentolamine 1 mg/kg, i.v. bolus). PYY reduced the 2-DG-stimulated secretion of gastric acid in a dose-dependent manner. PYY, given at 100 pmol.kg-1.h-1, reduced gastric acid output by 29 +/- 17%; PYY, at 200, by 41 +/- 7% (p < 0.05), and PYY, at 400, by 52 +/- 8% (p < 0.05). The inhibitory action of PYY on 2-DG-stimulated secretion of gastric acid persisted after treatment with phentolamine (69 +/- 14%; p < 0.05), but it was blocked by treatment with propranolol.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of endogenous prostaglandins in hormone-stimulated pancreatic exocrine secretion

The authors have previously shown that neurotensin and secretin inhibit gastric acid secretion in the dog and that these actions are inhibited by the prostaglandin synthesis inhibitor indomethacin. Conversely, neurotensin and secretin share similar stimulatory effects on pancreatic exocrine secretion. In the present study, the effects of blockade of prostaglandin synthesis by indomethacin on neurotensin-, cholecystokinin-, and secretin-stimulated exocrine secretion are examined along with the effects of these same agents on the release of pancreatic polypeptide. The studies were performed on conscious dogs with chronic gastric and pancreatic cannulas. Dose-dependent increases in pancreatic exocrine secretion of water and bicarbonate were observed with IV infusion of neurotensin or secretin; however, inhibition of prostaglandin synthesis by indomethacin abolished this response. Protein secretion stimulated by either neurotensin or cholecystokinin was not affected by prostaglandin inhibition. Cholecystokinin and neurotensin infusion stimulated release of pancreatic polypeptide; only neurotensin-stimulated release of pancreatic polypeptide was inhibited by indomethacin treatment. It is concluded that intact prostaglandin synthesis is necessary for the actions of neurotensin and secretin (but not that of cholecystokinin) on pancreatic exocrine secretion of water and bicarbonate and for neurotensin- (but not cholecystokinin-) stimulated release of pancreatic polypeptide.

New chronic gastric cannula for feeding ethanol liquid diet to young and old rats

Fifty-eight male Fischer-344 rats ages 5 and 23 mo were fed a liquid diet containing ethanol for 6 wk by means of a newly designed chronic gastric cannula that permitted maximum allowable freedom with minimum stress. Rats were weaned onto the Lieber-DeCarIi diet and fed 10 mL three times daily by bolus injection. With or without ethanol, the minimum daily intake of calories necessary to maintain body weight was determined to be approximately 150–160 kcal/kg/day for the young adult rats and 120–125 kcal/kg/day for the aged animals.

Stimulatory effect of pancreastatin on gastric acid secretion in conscious dogs

Pancreastatin, a new 49-amino acid peptide, has recently been isolated and characterized from extracts of the porcine pancreas. The objective of the present study was to examine the effect of various doses of pancreastatin on gastric acid secretion in conscious dogs that were prepared with chronic gastric cannulas. Pancreastatin, administered IV at 400 pmol · kg−1 · h−1, enhanced peptone meal [peptone (5%), phenylalanine (90 mmol/L), glucose (12 g/dL)]-stimulated gastric acid secretion by 50%; pancreastatin at 800 pmol · kg−1 · h−1 enhanced peptone meal secretion by 165% (P < 0.05). Intravenous administration of pancreastatin did not affect basal or peptone-stimulated release of gastrin. In addition, IV pancreastatin (400 pmol · kg−1 · h−1) failed to influence basal gastric acid secretion. Pancreastatin did not affect acid secretion stimulated by 2-deoxyglucose, histamine, or pentagastrin. The present study shows that pancreastatin can selectively enhance gastric acid secretion by a mechanism independent of cholinergic, histaminergic, or gastrin input.

Pancreatic glucagon does not alter intrameal gastric emptying of milk in the rat

The hypothesis that pancreatic glucagon (PG) inhibits feeding by altering intrameal gastric emptying was tested in nondeprived rats at midday, conditions under which exogenous PG is thought to elicit satiety. Rats received intraperitoneal injections of PG (400 or 800 μg/kg), cholecystokinin (CCK, 0.5 or 1.0 μg/kg) or saline and were given bolus intragastric infusions of 10 ml evaporated milk through chronic gastric cannulae. PG did not affect volumes of stomach contents recovered 20 minutes postinjection. In contrast, CCK inhibited gastric emptying in a dose-related manner. When milk was offered to the same rats to drink, 400 μg/kg PG significantly reduced meal size. These findings suggest that PG's satiety effect is not caused by its effect on stomach emptying.

Adenosine analogs inhibit gastric acid secretion

The potencies with which four adenosine deaminase-resistant analogs of adenosine affected the volume, pH and acid output of basal gastric acid secretions were examined in unanesthetized rats with chronic indwelling gastric cannulas. All four adenosine receptor agonists, R-phenylisopropyladenosine (R-PIA), S-phenylisopropyladenosine (S-PIA), N-ethylcarboxamide adenosine (NECA), and 2-chloroadenosine (CADO) significantly decreased gastric acid output in a dose-dependent manner. The rank order of potency was NECA, R-PIA > CADO > S-PIA. NECA and R-PIA were approximately equipotent in reducing gastric acid output. The levels of gastric acid output tended to increase at the lowest doses of the agonists. NECA decreased the volume of gastric secretion, whereas R-PIA had no effect on volume, but significantly increased the pH of the secretions. Valid measurements of pH in NECA-treated rats were not always obtainable because of near total inhibition of gastric secretions. S-PIA did not significantly affect volume, but increased pH at the higher doses tested. CADO decreased volume, but did not affect pH. These results indicate that adenosine analogs regulate not only the hydrogen ion concentration, but also the volume of gastric secretions.

CCK inhibits real and sham feeding in gastric vagotomized rats

We tested both sham feeding and real feeding in gastric vagotomized rats equipped with chronic gastric cannulas, either without pretest food deprivation or after 18 hr food deprivation. In each condition, 0.3–4 μg/kg CCK inhibited food intake similarly in control and vagotomized rats. Behavioral observations indicated the presence of normal postprandial satiety after CCK. We then tested real feeding in noncannulated rats after either total abdominal vagotomy, gastric vagotomy, or control operation. Doses of 0.5–4 μg/kg CCK had no effect on food intake after total vagotomy, but again inhibited feeding with equal potency in gastric vagotomized and control rats. The inhibitory effect of 6 μg/kg CCK was attenuated but not blocked by total vagotomy. Finally, we tested rats with gastric cannulas after gastric plus celiac vagotomy. CCK also inhibited both real and sham feeding after this lesion. These data confirm previous findings that abdominal vagal fibers mediate the satiety effect of moderate intraperitoneal doses of CCK, but fail to support the hypothesis that gastric branch fibers are the necessary vagal contribution.

Effect of bilateral ibotenic acid lesions in the basolateral amygdala on the sham feeding response to sucrose in the rat

To investigate the role of the basolateral amygdaloid complex in the sham feeding response to sucrose, rats received bilateral ibotenic acid lesions of the basolateral complex and were equipped for sham feeding with implanted chronic gastric cannulas. Rats were also tested on different days with 2.5%, 5%, 10%, and 40% sucrose. After 17 hours of food deprivation, bilateral, amygdaloid-lesioned rats sham fed significantly less 2.5% sucrose than sham operated (control) rats. After no deprivation, amygdaloid-lesioned rats sham fed significantly less 5% sucrose than control rats. Under both deprivation conditions, however, sham intake was a function of sucrose concentration in both groups of rats and the sham feeding responses of lesioned and control rats to 10% and 40% sucrose were similar. These results demonstrate that cells in the basolateral amygdaloid complex are necessary for the normal sham feeding response to concentrations of sucrose less than 10%, but not for the response to higher concentrations of sucrose.

A new in vivo method for repeatedly studying gastric acid secretion and other secretory parameters in awake guinea pig

A new model for measuring gastric secretory parameters in awake guinea pigs is described. A chronic cannula was surgically implanted in the stomach of each guinea pig. The rates of gastric secretion and changes in intragastric volume were measured using a dye dilution technique. In contrast to previous techniques in small laboratory animals, there was no collection of gastric juice via drainage, no oral intubation for aspiration was involved, no special or sophisticated equipment was used, no anesthesia was employed, and there was no stress associated with acute surgery. This method offers a valuable advantage by combining the chronic gastric cannula with a dye dilution technique in that the same animal can be used several times and finally, several gastric secretory parameters can be measured simultaneously. The animals were used from 3 weeks to 10 months after surgery and as many as 15 studies were performed on the same guinea pig. Samples were collected at 10-min intervals and analyzed for acid and dye concentration from which the onset and kinetics of gastric secretion were followed. Basal gastric secretion (11.8 ± 1.6 μeq/kg/min; all mean ± 1 SEM) was increased within 20 min after subcutaneous infusion of histamine (30 μg/kg/hr) and peaked by 40–60 min at a mean acid output rate of 41 ± 3 μeq/kg/min. Histamine also increased the intragastric volume from 6.3 to 13.4 ml as it increased fluid output from 1.6 ± 0.1 ml/10 min to 3.4 ± 0.2 ml/10 min. The increase in acid output caused by histamine was inhibited by the H 2-antagonists cimetidine (3 μmole/kg) and ranitidine at 0.5 μmole/kg. Omeprazole (1.2 μmole/kg), an HK-ATPase inhibitor, almost abolished acid output under both basal and histamine-stimulated conditions. Thus, the present method is simple and suitable to study the physiology and pharmacology of gastric secretion in the guinea pig with a particular emphasis on the action of histamine. Furthermore, because of the species involved, there is also a significant economical advantage and the guinea pig can also be used as a potential model for studying experimental ulcer.

Sham feeding experience produces a conditioned increase of meal size

The effect on intake of reversing the flavors and locations that had been associated with sham feeding and real feeding was measured in two experiments. Rats were equipped with chronic gastric cannulas to permit sham feeding. Flavors and locations were associated with a real meal of milk or with sham feeding the same volume of flavored milk or with sham feeding about six times as much milk. In both experiments, the flavors and locations with sham feeding produced a conditioned increase in meal size during real feeding. This conditioned increase in meal size appeared to be primarily due to a conditioned decrease in the satiating potency of the milk because it was dissociated from a conditioned increase in preference measured in a four-minute choice test.

Preparation and maintenance of rats with chronic esophagostomy and gastric cannula

We describe surgical and maintenance procedures for the “double-fistula” preparation in rat. Rats are prepared with esophageal fistulas, so that material swallowed escapes from an opening in the throat; and with gastric cannulas that permit both nutritional and hydrational maintenance, and the experimental intubation of fluids directly into the stomach.

Capsaicin effects on stress pathology and gastric acid secretion in rats

The effects of capsaicin on stress ulcer formation, plasma corticosterone levels and gastric acid secretion were examined in rats. Capsaicin desensitization did not affect restraint stress ulcer formation but was associated with markedly elevated corticosterone levels, even in non-stressed rats. Acute, orally administered capsaicin augmented ulcer formation only if its administration was followed immediately by restraint stress. Delays of 1,2, or 3 h between drug administration and stress produced ulceration comparable to control values. Capsaicin did not affect basal (non-stimulated) gastric acid secretion but substantially decreased pentagastrin-stimulated acid output. Capsaicin is a major pungent ingredient in a variety of red peppers (species capsicum used as spices in many countries. Capsaicin has been implicated as an etiologic factor in gastrointestinal disease, especially in countries where its use is prevalent (1), however, relatively few studies have examined how capsaicin affects gastrointestinal physiology and pathology. Acute, orally administered capsaicin has been associated with erosive gastritis in rats which could be prevented by pretreatment with histamine H 2 receptor antagonists (2). These data suggested that capsaicin influences histamine-mediated processes in the gut, rather than exerting a direct cytotoxic effect on the mucosal surface. Further evidence favoring this hypothesis was provided by Limlowwongse et al. (1) who showed that oral capsaicin increased gastric acid output in a dose-related fashion in anaeshetized rats. Both hexamethonium and atropine abolished this effect, suggesting that capsaicin may act by influencing cholinergic (vagal) activity associated with the gut. More recently, Szolcsanyi and Bartho (3) proposed that capsaicin exerts a dual action in the stomach. Acute, orally administered, low doses of capsaicin were found to protect rats against development of pyloric-ligation-induced ulcers. However, chronic subcutaneous administration of capsaicin, which produces desensitization (4), and which itself produced no gastric damage, was found to exacerbate subsequent pyloric-ligation-induced ulcers. The authors suggested that acute capsaicin treatment facilitates the release of substances from sensory nerve endings (substance P) which would enhance mucosal blood flow and buffer excess gastric secretion. A chronic, desensitizing regimen of capsaicin, however, would result in diminsshed release from these sensory nerve endings, reduce the extent of gastric vasodilation, and augment ulcer formation. Other studies examining capsaicin effects on the stomach, and in particular, studies employing more physiological models of gastric function are rare. The physiological relevance of studying anaesthetized rats and pyloric-ligation-induced gastric damage has been questioned (5,6) but this model is useful for examining gastric secretory function. However, one useful experimental model is that of stress ulcer, which has emerged as a new diagnostic category over the last decade and which is particularly relevant to human stress ulcer disease (6,7). These ulcers are especially common in infants, the elderly, and among patients in intensive care units following severe trauma, septic shock, burns, and intracranial disease or traumatic head injury. They are characterized by upper gastrointestinal bleeding which can result in a mortality rate of approximately fifty percent (7). Stress ulcers can be reliably produced in animals and such models are essential for understanding the pathogenesis of this disease. Restraint or immobilization is a simple, effective and reproducible animal model of stress ulcer (8,9) and is associated with a reliably high incidence of histologically verifiable ulcers (penetrating the muscularis ) (8) and which respond to current therapeutic regimens, for example, histamine H 2 receptor blockade (10). A second relevant and widely used animal model of gastric function is the chronic gastric cannula preparation (11). In this method, chronic, indwelling gastric cannulae are implanted in the rat forestomach and following a recovery period, conscious gastric acid secretion can be repeatedly sampled from the animals without contaminating effects from anaesthetics or surgery. Accordingly, in the present study, we examined (1) the effects of capsaicin on conscious gastric acid secretion in chronic gastric cannula rats and (2) the effects of capsaicin on stress ulcer and stress pathology in rats.

Release of secretin by licorice extract in dogs.

To determine the effect of a fraction of licorice extract, FM100, on the endogenous release of secretin and exocrine pancreatic secretion, five dogs were prepared with chronic pancreatic fistulas and gastric cannulas. Intraduodenal administration of licorice extract (pH 7.4) in three different doses (0.5, 1.0, and 2.0 g) resulted in significant increases of both plasma secretin concentrations and pancreatic bicarbonate secretion in a dose-related manner. The plasma secretin concentration and pancreatic bicarbonate output produced by licorice extract correlated well. Intragastric administration of licorice extract (2 g) in 5% liver extract meal (in which pH was maintained at 5.5 by the intragastric titration method) resulted in significant increases of both plasma secretin concentration and pancreatic bicarbonate output. The increase in pancreatic bicarbonate secretion was completely abolished by intravenous infusion of a rabbit antisecretin serum in the two dogs so studied. Thus, the present study indicates that the endogenous release of secretion is involved in a mechanism of an increase in exocrine pancreatic secretin induced by FM100.