Infusion Of Secretin Research Articles

Inhibition of Cholecystokinin-Stimulated Pancreaticobiliary Output in Man by the Cholecystokinin Receptor Antagonist MK-329

MK-329 (formerly L-364,718) is a new nonpeptide antagonist for the peripheral (type-A) cholecystokinin (CCK) receptor, which has proved effective in blocking the actions of both exogenous and endogenous CCK in several species. To evaluate the effect of MK-329 on CCK-stimulated pancreaticobiliary output in man, six normal subjects received 10 mg MK-329 or placebo orally in a randomized, crossover fashion, before a background intravenous infusion of secretin (5 pmol/kg/h) and two doses of CCK-8 (approximately 15 and 40 pmol/kg/h, each for 1 h). Gastric and duodenal juice were aspirated separately via two double-lumen tubes, with 51Cr-ethylene-diaminetetraacetic acid as a duodenal marker. After placebo treatment the background infusion of secretin produced maximum plasma concentrations of secretin similar to postprandial values, averaging about 5 pM. After placebo treatment the low dose CCK-8 infusion (15 pmol/kg/h) increased circulating CCK concentrations from basal levels of 1.8 +/- 0.2 pM to levels similar to those observed postprandially, averaging 9.2 +/- 1.3 pM, and the high dose of CCK-8 (40 pmol/kg/h) induced supraphysiologic levels of CCK, averaging 23.4 +/- 3.2 pM. Plasma concentrations of secretin and CCK were not significantly different during MK-329 treatment. As expected, infusion of CCK-8 at both doses stimulated pancreatic exocrine secretion and gallbladder contraction in placebo controls, as indicated by increases in the output of trypsin, amylase, bicarbonate, and bilirubin. Whereas MK-329 did not significantly reduce basal pancreatic secretion, the integrated incremental output of trypsin, amylase, and bicarbonate in response to stimulation with the low (physiologic) CCK dose was inhibited by 74% (p less than 0.01), 89% (NS), and 75% (p less than 0.05), respectively. Basal bilirubin output was virtually abolished after treatment with MK-329, and the response to the low dose of CCK was reduced by 98% (p less than 0.01), indicating almost complete inhibition of gallbladder contraction at physiologic circulating concentrations of CCK. It is concluded that MK-329 is an orally active antagonist of CCK-stimulated pancreaticobiliary output in man and could thus be utilized to explore the physiologic regulation of the exocrine pancreas and gallbladder by CCK.

Vasoactive Intestinal Peptide and Secretin: Effects of Combined and Separate Intravenous Infusions on Bile Secretion in Man

The effects of intravenously administered vasoactive intestinal peptide (VIP) and secretin on bile secretion were studied in 12 patients with complete biliary fistulas. The two peptides were administered both simultaneously and separately. During VIP infusion bile volume increased by 60%, and during the combined VIP and secretin infusion bile volume increased by another 70%. VIP increased bile bicarbonate concentration by some 30%. Although secretin did not increase the concentration, bicarbonate output increased threefold during secretin infusion but only twofold during VIP infusion. The outputs of bile acids were not significantly affected by the two peptides, whereas the concentrations decreased by 40% and 70% after VIP and secretin, respectively. The canalicular bile flow, measured by [14C]erythritol, was unaffected by VIP infusion, whereas secretin alone and the combination of the two peptides increased the canalicular clearance by 80%. The choleretic effect of VIP thus seems to occur only at the ductular level. Secretin exerts its effect at the ductular level and possibly also at the canalicular level. It is concluded that the two peptides have additive effects on the ductular bile flow.

Somatostatin Analog, SMS 201-995, Inhibits Pancreatic Exocrine Secretion and Release of Secretin and Cholecystokinin in Rats

We studied the effect of a synthetic octapeptide somatostatin analog, SMS 201-995 (sandostatin), on pancreatic exocrine secretion and on plasma secretin and cholecystokinin (CCK) levels in vivo in anesthetized rats. The exocrine pancreas was stimulated by either intravenous infusion of both secretin (0.06 CU/kg/h) and cholecystokinin octapeptide (CCK-8) (0.03 micrograms/kg/h) or intraduodenal infusion of oleic acid (pH 6.5) in a dose of 0.25 mmol/h. Intravenous administration of SMS 201-995 in three different doses of 100, 200, and 400 ng/kg/h resulted in dose-related inhibition of pancreatic secretion in terms of volume, bicarbonate, and amylase stimulated by exogenous secretin and CCK. Intraduodenal oleic acid stimulated pancreatic secretion, including volume, bicarbonate, and amylase, and this was accompanied by a significant elevation in the plasma concentrations of secretin and CCK. Intravenous administration of SMS 201-995 in the three different doses described above caused dose-dependent suppression of the increase in pancreatic exocrine secretion as well as the plasma concentration of secretin and CCK induced by intraduodenal infusion of oleic acid. It is concluded that SMS 201-995 inhibits pancreatic exocrine secretion and the release of endogenous hormones, such as secretin and CCK, in rats.

Prolactin response to secretin during the spontaneous menstrual cycle in women.

The effect of an intravenous infusion of secretin (2.0 CU/kg/h) on serum prolactin (PRL) and estradiol levels and plasma levels of vasoactive intestinal polypeptide and somatostatin (SRIH) was studied in 8 healthy and normally cycling women during the midfollicular phase (cycle day 7), at midcycle (day 14), and during the midluteal phase (day 21) of the menstrual cycle. When compared to basal preinfusion levels, a significant decrease in serum PRL levels was observed at steady state concentrations of plasma secretion (+30 to +60 min) both during the follicular (p less than 0.03) and the luteal (p less than 0.0001) phases. At midcycle a nonsignificant decrease was observed. A significant and negative correlation existed between serum PRL and plasma secretin levels in the follicular phase (r = -0.33; p less than 0.05) and in the luteal phase (r = 0.73; p less than 0.0001). The plasma concentrations of SRIH increased significantly at steady state conditions of secretin at midcycle (p less than 0.02) and in the luteal phase (p less than 0.04), while no effect was found during the follicular phase. A significant and positive correlation between plasma levels of SRIH and secretin was observed at midcycle (r = 0.63; p less than 0.002) and in the luteal phase (r = 0.46; p less than 0.02). No effect of secretin on plasma vasoactive intestinal polypeptide and serum estradiol concentrations was demonstrated. These results suggest that the suppression of PRL in the follicular phase of the spontaneous menstrual cycle can be ascribed to an effect of secretin alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Failure of secretin to exert an ameliorative effect on acute reflux pancreatitis in the rat

This study was undertaken to evaluate the possible ameliorative effect of secretin on acute reflux pancreatitis in the rat. Thirty days after the performance of a gastrojejunal anstomosis, in all rats (36 Sprague-Dawley, mean weight 250 g) acute pancreatitis was induced by creating a closed duodenal loop for 12 h. In the subsequent 12 h group A (14 rats) received continuous intra-arterial infusion of secretin (5 CU/kg/h); group B (22 rats) received equal volumes of saline solution. Serum amylase and pancreatic histology were evaluated. In group B a mild form of pancreatitis was observed, since the mean values of haemorrhage, necrosis and steatonecrosis, indices of severe disease, were found to be low. Group A presented similar results. No difference was documented between the two groups for both the histological findings and serum amylase. We can conclude that despite the reported protective and ameliorative effects of secretin in cerulein-induced acute pancreatitis in the rat, our data do not support a similar action of secretin in the closed duodenal loop model.

Pancreatic Secretory Responses to Long-Term Infusions of Secretin and Cerulein in Humans

We measured pancreatic enzyme and bicarbonate responses to graded doses of intravenous secretin or cerulein alone or together in healthy human subjects. Bicarbonate responses were steady and well maintained during the last 3.5 h of the 4 h of infusions of secretagogues, giving evidence for a constant pancreatic flow rate. Potentiation (more-than-additive response) was observed between secretin and cerulein for bicarbonate secretion, but not for enzyme secretion. Secretin stimulated pancreatic enzyme secretion. The effect was most pronounced with amylase secretion and less prominent with lipase, trypsin, and chymotrypsin secretion. Changes in the proportion of enzymes were seen over time, with trypsin and chymotrypsin output declining towards the end of cerulein infusion. We conclude that in humans the effects of secretin on pancreatic enzyme secretion are complex and include time-dependent changes in the enzyme mixture, but potentiation between secretin and cerulein does not occur for enzyme output.

Plaunotol inhibits postprandial gastrin release by its unique secretin-releasing action in humans

Plaunotol, an acrylic diterpene alcohol, is a new antiulcer agent derived from the "plau-noi" plant and has been reported to stimulate the release of endogenous secretin in humans. We investigated the effect of plaunotol on postprandial gastrin release, comparing it to the effect of exogenous secretin in a physiological dose in eight healthy volunteers. Four sets of experiments were performed in each volunteer: (1) meal alone, (2) meal after intravenous ranitidine (50 mg), (3) meal after oral administration of plaunotol (320 mg) in addition to ranitidine, and (4) meal after ranitidine with simultaneous intravenous infusion of secretin (0.03 CU/kg/hr). The postprandial increase in plasma secretin concentration was significantly reduced by ranitidine, while postprandial gastrin release was markedly exaggerated. Plaunotol in combination with ranitidine significantly increased secretin release and inhibited gastrin release after a meal. Intravenous infusion of secretin resulted in significant suppression of postprandial gastrin release exaggerated by ranitidine. The present study indicates that plaunotol inhibits postprandial gastrin release by its unique secretin-releasing action.

Effect of acid-base balance on biliary bicarbonate secretion in the isolated perfused guinea pig liver

Secretin-induced choleresis is of ductal origin and involves bicarbonate transport. Its mechanism is unknown. To determine the relative effects of systemic pH, PCO2, and bicarbonate concentration on secretin-stimulated bicarbonate transport, states of acute metabolic and respiratory acidosis or alkalosis were created in isolated perfused guinea pig livers with or without secretin infusion. During spontaneous secretion conditions, biliary bicarbonate secretion was not correlated with perfusate pH (7.19-7.62) or perfusate PCO2 (23.9-59.7) but was significantly correlated with perfusate bicarbonate concentration (17.5-37.9 mM). Under secretion infusion (25 mU/min), bile flow and biliary bicarbonate concentration increased significantly (109 and 51%, respectively). Biliary bicarbonate secretion was not correlated with perfusate pH (7.19-7.60) but was significantly correlated both with perfusate bicarbonate concentration (14.6-36.8 mM) and PCO2 (25.8-54.3 mmHg). Spontaneous and secretin-induced bile flow were correlated with biliary bicarbonate concentration. The correlation between biliary bicarbonate secretion and PCO2 during secretin-induced choleresis supports the hypothesis that secretin-induced biliary bicarbonate secretion could, at least in part, involve a transport of H+ (or OH-) rather than HCO3- itself and that intracellular pH could play a role in the regulation of this secretion. Amiloride (5 X 10(-4) M) did not influence secretin-induced biliary bicarbonate secretion. This result suggests that the Na(+)-H+ exchange is not involved in bicarbonate secretion by ductular cells.

Structural and Functional Effects of Long-Term Alcohol Administration on the Dog Exocrine Pancreas Submitted to Two Different Diets

Our purpose was to study the influence of two different levels of dietary protein and fat on the action of chronic alcohol feeding on the exocrine pancreatic secretion and the pancreatic morphology of conscious dogs. Ten animals were provided with gastric and duodenal cannulas. Five of them (group H) received a high-protein (39% of calories), high-fat (34%) diet, and the five others (group L) a moderately low-protein (15%), low-fat (20%) diet. Animals were housed in closed kennels lightened with artificial light and did not have free access to sunlight. Five series of experiments were performed just before and 5 and 12 months after daily alcohol administration through the gastric cannula (2 g/kg/day). Volume, bicarbonate, and protein were measured under basal conditions after intragastric ethanol infusion (1.5 g/kg), under hormonal stimulation with 1 clinical unit (CU)/kg/h secretin or 1 CU/kg/h secretin plus 3 Crick Harper Rate (CHR) U/kg/h cholecystokinin (CCK), before and after intravenous ethanol 1.3 g/kg for 20 min, and after intragastric ethanol (1 g/kg) given with a meal. Group H was the most sensitive to the action of chronic alcohol feeding. At the end of 1 year of alcohol administration, volume and bicarbonate were not affected, but protein secretion was significantly increased in basal conditions and under secretin infusion, but not under CCK infusion or in response to a meal. The secretory pattern of these dogs was different from the response of dogs studied in previous experiments having the same diet but housed in an open kennel and having free access to outside and sunlight. In group L, protein was less affected, but volume and bicarbonate were significantly decreased 1 year under secretin stimulation. Histological damages were seen in the two groups characterized by a slight periacinar fibrosis and alterations of ductal cells. Acinar and ductal luminae were dilated and filled with protein plugs also present in pancreatic juice and able to stop the flow of juice. At the difference from human beings, these plugs were built up of all secretory protein but not of an insoluble fibrillar molecular form of pancreatic stone protein. This study confirms the role of chronic alcoholism on the formation of protein plugs and shows the influence of nutritional and environmental conditions.

Effects of pancreatic polypeptide on biliary flow and bile acid secretion stimulated by secretin and cholecystokinin in the conscious pig

Fourteen castrated male Large White pigs, weighing 42.5 ± 1.0 kg, were fitted with biliary and duodenal fistulae for biliary secretion studies. Furthermore, catheters were placed in a carotid artery for blood sampling and in a jugular vein for peptide infusion. Bile was automatically restituted to the animals and continuously sampled for analysis on experimental days. Following an 8 day recovery period, infusion studies were performed after an overnight fast. After a 30 min basal period, sustained biliary flow and bile acid output were obtained and maintained throughout the assay with secretin (36 pmol/kg/h) and CCK-8 (600 pmol/kg/h) infusion. Then, 200, 400, 600, 800 or 1200 pmol/kg/h of porcine pancreatic polypeptide (PP) were infused for 60 min. Secretin plus CCK infusion was continued for 1 h after PP infusion was stopped. Each dose of PP was given on a separate day. Biliary flow was not affected by PP except for the dose of 400 pmol/kg/h. On the contrary, bile acid concentration and output decreased with the lowest dose of PP (200 pmol/kg/h). As soon as the first dose of PP was infused, bile acid concentration and output fell to about 60% of values obtained with secretin plus CCK. Plasma levels of PP were below or similar to postprandial values for 200, 400 and 600 pmol/kg/h and they were significantly larger with 800 and 1200 pmol/kg/h. Bile acid concentration and output did not return to values obtained with secretin plus CCK infusion after cessation of PP infusion. In conclusion, porcine PP given in physiological doses to the pig decreases bile acid output whereas biliary flow remains unaffected.

Secretion of gamma-glutamyltranspeptidase by the pancreas: Evidence for a membrane shedding process during exocytosis

Gamma Glutamyltranspeptidase (GGT) is a membrane-bound enzyme involved in glutathione metabolism. It is present in rat exocrine pancreas at a level which is only exceeded by the kidney. It has been previously shown that most of the enzyme activity is located in the apical area of the acinar cell, more precisely at the level of zymogen granules and plasma membrane. The aim of the present study was to examine the secretory behavior of that enzyme. Under resting conditions, in vivo, high levels of GGT were found in pancreatic juice and its level was not related to protein concentration. Under secretin infusion, a relatively constant level of GGT was released, and again, there was no correlation between enzyme activity and protein concentration. Following a bolus injection of caerulein, an analog of cholecystokynin, marked and concommitant rises in protein and GGT levels were observed. Ultracentrifugation, as well as gel filtration on Sepharose 4B, demonstrated that the enzyme was not released in a soluble form. This observation is in agreement with in vitro determinations on isolated zymogen granules showing that GGT is totally associated with the ZG membrane and undetect-able in the content of these organelles. The present data show that 1° GGT is released from the rat pancreas acinar cells in a particulate form; 2° GGT release is elicited by hormonal stimulation coinciding with the exocytotic release of secretory proteins. Our observations lead us to propose that in rat pancreas, ZG membrane fragments are released along with secretory proteins during exocytosis.

Inhibition of Human Gastric Acid Secretion by Peptide YY and Secretin

In 6 healthy volunteers we investigated the effect of secretin and peptide YY (PYY) on gastric acid secretion stimulated by pentagastrin (100 ng/kg/h). Secretin (0.05 CU/kg/h) and PYY (10.0 pmol/kg/h) were given intravenously either alone or in combination. Given alone secretin and PYY inhibited gastric acid output by 25 and 21%, respectively. The combined infusion of secretin and PYY inhibited acid output by 38% indicating an additive effect. The infusion of one hormone did not influence release of the other. It is suggested that the interaction of PYY and secretin on pentagastrin-stimulated gastric acid secretion in normal man is of the additive type.

Somatostatin inhibits the effect of secretin on bile flow and on hepatic bilirubin transport in the rat.

Increasing amounts of porcine secretion (0.05 to 2.00 clinical units/h/100 g body wt) given to rats during a continuous infusion of bilirubin, increased bile flow and the apparent maximal biliary excretion of bilirubin ('Tm'). This increment was caused by an enhanced biliary output of bilirubin monoconjugates. The effect was dose dependent but maximal at a secretin infusion of 0.80 CU. Somatostatin 0.2 and 0.8 microgram/h/100 g body wt caused a dose related inhibition of the hepatic effects of secretin both on bile flow and on biliary output of bilirubin conjugates. As secretin elicits the release of somatostatin, a feed-back system could be envisaged whereby the somatostatin released stops the effects of secretin.

Ovarian carcinoma as a cause of Zollinger-Ellison syndrome: Natural history, secretory products, and response to provocative tests

Zollinger-Ellison syndrome is usually caused by a gastrin-secreting tumor in or near the pancreas. We describe a patient in whom an ovarian cystadenocarcinoma was the cause of the syndrome. The patient presented with a short history of peptic ulceration and development of a large pelvic mass. Investigations demonstrated a basal acid output of 37.8 mEq/h and a maximal acid output of 36.0 mEq/h, and the plasma concentration of gastrin was 830 pg/ml (normal < 100). Secretin and calcium infusion tests were positive, and a meal test was compatible with Zollinger-Ellison syndrome. Imaging studies demonstrated a normal liver and pancreas but a large cystic right ovarian mass. Resection of the mass resulted in a marked reduction in gastric acid output, a fall in plasma gastrin concentration to normal, negative calcium and secretin tests, and a normal (positive) meal test. Histology of the mass showed it to be a mucinous cystadenocarcinoma. The tumor stained with immunoperoxidase technique was positive for gastrin, and the cyst fluid contained high concentrations of gastrin and calcitonin. One year later, the patient has no biochemical or imaging evidence of tumor. Ovarian, gastrin-producing tumors and pancreatic gastrinomas cannot be distinguished by provocative tests, and negative imaging studies do not exclude a pancreatic tumor. Patients with an ovarian mass and Zollinger-Ellison syndrome should have a bilateral oophorectomy and a careful exploration of the pancreatic area.

Evaluation of sphincter of Oddi function.

Disorders of sphincter of Oddi motility are being recognized as a cause for post-cholecystectomy pain. Objective diagnosis of sphincter of Oddi dysfunction is difficult because of the relative inaccessibility of the sphincter. In recent years, a number of investigations have been used in order to diagnose motility disorders of the sphincter of Oddi. The most useful of these investigations is endoscopic manometry. However, in addition, the morphine neostigmine provocation test, radioscintigraphy to assess bile flow, and assessment of pancreatic duct diameter following secretin infusion have been used. Specificity and sensitivity for all of these investigations of sphincter of Oddi function have been difficult to obtain due to the small number of patients and the heterogeneity of sphincter of Oddi abnormalities. Based on the manometry measurements, two major subgroups of sphincter of Oddi dysfunction have been defined. One group of patients exhibits a high basal pressure consistent with stenosis and the second demonstrates a number of dyskinetic patterns. Prospective studies currently underway will best define the most appropriate therapy for these disorders.

Inhibitory effect of calcitonin on pure human pancreatic secretion.

The inhibitory effect of calcitonin on human pancreatic secretion was evaluated to examine whether the different results reported earlier between humans, cats and dogs can be ascribed to the different sensitivity of these species to calcitonin, as suggested by some investigators. Pancreatic juice was obtained by endoscopic cannulation of the pancreatic duct from 11 patients with relapsing pancreatitis during intravenous infusion of secretin (1 U/kg/h) plus caerulein (0.04 microgram/kg/h). After steady secretion was attained 20 min after the beginning of collection, five 2-min fractions were obtained before, and ten 2-min fractions were obtained after intravenous infusion of calcitonin (1 IU/kg/h). The pre- and post-calcitonin fractions from each patient were compared by Student's t-test. Calcitonin inhibited the secretory volume (26.8 to 65.6%) and bicarbonate secretion (21.4 to 62.0%) in 8 patients, and amylase (48.4 to 89.5%) and lipase secretion (47.4 to 90.5%) in all patients. The present studies reconfirmed that prominent inhibition of enzyme secretion occurs in humans. A new finding was that significant inhibition of the secretory volume and bicarbonate secretion occurs in humans. The inhibitory effects of calcitonin in humans did not appear to differ from those in cats and dogs, when evaluated similarly with the use of pure pancreatic juice.

Biliary and pancreatic excretion of cefamandole.

After intravenous infusion of secretin and cholecystokinin in six dogs, cefamandole (50 mg/kg of body weight) was given intravenously for 10 min. Samples of serum, bile, pancreatic juice, liver, pancreas, fat, and muscle were collected over a 2-h period. Cefamandole levels were measured by a microbiological assay. The highest levels were as follows: serum, 160 micrograms/ml; bile, 3,071 micrograms/ml; pancreatic juice, 7 micrograms/ml; liver, 101 micrograms/g; pancreas, 44 micrograms/g; muscle, 20 micrograms/g; and fat, 14 micrograms/g. Levels in pancreatic juice were extremely low compared with levels in pancreatic tissue, suggesting the existence of a barrier to excretion at the ductal membrane.

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.

Effect of Low-Dose Exogenous Secretin and Somatostatin on Pentagastrin-Stimulated Gastric Acid Secretion in Man

The inhibitory effect of intravenous infusion of secretin (0.05 CU kg-1h-1) and somatostatin (60 pmol kg-1h-1), given alone or in combination, on pentagastrin-stimulated (100 ng kg-1 h-1) acid secretion was studied in 10 healthy subjects. Secretin inhibited acid secretion by 54% (p less than 0.05), and somatostatin inhibited by 70% (p less than 0.05). The combined infusion of secretin and somatostatin decreased acid output by 64% (p less than 0.05). The differences between the three groups were not significant (p greater than 0.05). Median plasma concentrations of secretin and somatostatin were of the same magnitude as seen after duodenal acidification. The present study did not demonstrate any interaction between secretin and somatostatin in the inhibition of gastric acid secretion.

Alpha-adrenergic influences on exocrine pancreatic secretion in the rabbit

Action of phenylephrine (35 micrograms/Kg/min) alone or previously blocked by phentolamine (100 micrograms/Kg/min) on exocrine pancreatic secretion of anaesthetized rabbits has been studied, in basal state or under stimulation by secretin (1 C.U./Kg/h) or by the octapeptide of cholecystokinin (OP-CCK) (0.15 Ivy dog units/Kg/h). Phenylephrine increased arterial pressure. This effect was blocked by phentolamine. However no variations were seen in pancreatic blood flow in any of the experimental conditions assayed. Phenylephrine produced a secretin-like effect on hydroelectrolytic secretion in basal conditions. This action was maintained after the infusion of secretin but not after OP-CCK. This effect was not blocked by phentolamine. Phenylephrine increased protein secretion in the basal state, an action that was blocked by phentolamine. After secretin or OP-CCK stimulation phenylephrine did not increase protein secretion. It is concluded that phentolamine blocks the effects of phenylephrine on acinar cells but not on ductular cells.