Biomedical subjects

I De Dios

Publications and source records attributed to I De Dios.

At least 19 recordsLinked to original sources

PubMed2003

N-acetylcysteine prevents intra-acinar oxygen free radical production in pancreatic duct obstruction-induced acute pancreatitis.

Although oxygen free radicals (OFR) are considered to be one of the pathophysiological mechanisms involved in acute pancreatitis (AP), the contribution of acinar cells to their production is not well established. The aim of the present study was to determine the effect of N-acetylcysteine (NAC) in the course of AP induced by pancreatic duct obstruction (PDO) in rats, directly analysing by flow cytometry the quantity of OFR generated in acinar cells. NAC (50 mg/kg) was administered 1 h before and 1 h after PDO. Measurements by flow cytometry of OFR generated in acinar cells were taken at different PDO times over 24 h, using dihydrorhodamine-123 as fluorescent dye. Histological studies of pancreas and measurements of neutrophil infiltration in the pancreas, pancreatic glutathione (GSH), malondialdehyde (MDA) levels, plasma amylase activity and hemoconcentration were carried out in order to assess the severity of AP at different stages. NAC effectively blunted GSH depletion at early AP stages and prevented OFR generation found in acinar cells as a consequence of AP induced by PDO. This attenuation of the redox state impairment reduced cellular oxidative damage, as reflected by less severe pancreatic lesions, normal pancreatic MDA levels, as well as diminished neutrophil infiltration in pancreas. Hyperamylasemia and hemoconcentration following AP induction were ameliorated by NAC administration at early stages, when oxidative stress seems to be critical in the development of pancreatitis. In conclusion, NAC reinforces the antioxidant defences in acinar cells, preventing OFR generation therefore attenuating oxidative damage and subsequently reducing the severity of PDO-induced AP at early stages of the disease.

Acetylcysteine↗

PubMed2003

Major pathological mechanisms of acute pancreatitis are prevented by N-acetylcysteine.

AIM: To analyze the capability of N-acetylcysteine (NAC) to prevent major intra-acinar pathogenic mechanisms involved in the development of acute pancreatitis (AP). METHODS: AP was induced by pancreatic duct obstruction (PDO) in rats. Some animals received NAC (50 mg/kg) 1 h before and 1 h after PDO. During a 24-hour period of PDO, plasma amylase activity and pancreatic glutathione and malondialdehyde levels were measured. Cytosolic Ca(2+) levels and enzyme (amylase and trypsinogen) load in acinar cells were also analyzed by flow cytometry, and histological analysis of the pancreas was performed by electron microscopy. RESULTS: NAC avoided glutathione depletion at early AP stages, thereby preventing pancreatic oxidative damage, as reflected by normal malondialdehyde levels. By limiting oxidative stress, NAC treatment effectively prevented the impairment of Ca(2+) homeostasis found in acinar cells from early AP onwards, thus protecting the pancreas from damage. In addition, lower quantities of digestive enzymes were accumulated within acinar cells. This finding, together with the significantly lower hyperamylasemia observed in these animals, suggests that NAC treatment palliates the exocytosis blockade induced by PDO. CONCLUSION: By preventing oxidative stress at early AP stages, NAC administration prevents other pathological mechanisms of AP from being developed inside acinar cells, thus palliating the severity of disease.

Acetylcysteine↗

PubMed2000

Enzyme load in pancreatic acinar cells is increased in the early stages of acute pancreatitis induced by duct obstruction in rats.

Trypsinogen and amylase content has been analysed by flow cytometry in individual pancreatic cells from rats with acute pancreatitis induced by pancreatic duct obstruction, from the earliest stages to 48 h after obstruction. Parallel morphological studies of the pancreas by electron microscopy and analysis of various parameters for the diagnosis of pancreatitis will allow research into the possible relationship between intracellular enzyme load and the severity of pancreatitis. Progressive increases in amylase activity in ascites and plasma, the volume of ascites, haematocrit, vacuolization, oedema and macrophage infiltration were observed between 1.5 h and 12 h after duct obstruction. A progressive increase in enzyme content was also observed in individual acinar cells at this stage. Interestingly, the larger increase was for trypsinogen, so that the trypsinogen/amylase ratio was significantly increased in all acinar cells by 12 h after duct obstruction. This represents a risk factor for the development of pancreatitis. Sections of pancreas taken from rats that had duct obstruction for 48 h showed massive dilatation and disorganization of the endoplasmic reticulum, focal apoptosis and necrosis. These severe alterations would affect enzyme synthesis, as reflected by the significant decrease in the intracellular enzyme load observed at this stage. However, not all acinar cells were affected equally by the damage induced by pancreatitis: R(1) cells appeared to be more sensitive than R(2) cells. In conclusion, intracellular accumulation of digestive enzymes occurs at early stages of pancreatitis, and this effect is proportionally greater for trypsinogen, a finding that could explain the degree of severity achieved in the course of pancreatitis.

Acute Disease↗

PubMed1999

The recovery of acute pancreatitis depends on the enzyme amount stored in zymogen granules at early stages.

Little is known about the changes in pancreatic enzyme storage in acute pancreatitis. We have performed flow cytometric studies of zymogen granules from rats with acute pancreatitis induced by hyperstimulation with caerulein. A comparison was made with rats treated with hydrocortisone (10 mg/kg/day) over 7 days before inducing pancreatitis in order to find out whether the amount of enzymes stored in the pancreas plays a key role in the development of pancreatitis. The potentially therapeutic effect of L-364,718 (0.1 mg/kg/day, for 7 days), a CCK receptor antagonist, was assayed in the rats with caerulein-induced pancreatitis which had previously received the hydrocortisone treatment. A significant increase in the intragranular enzyme content was observed 5 h after hyperstimulation with caerulein. The highest values were reached in the rats previously treated with hydrocortisone. The greatest pancreatic enzyme load was parallel to the highest values in plasma amylase, edema and haematocrit observed. Acute pancreatitis was reversed seven days later. At this stage smaller granules appeared in the pancreas whose enzyme content was similar to that of controls when no treatment was applied after pancreatitis. In contrast, L-364,718 administration prevented the favourable evolution of pancreatitis since the antagonism exerted on CCK receptors induced a blockade of secretion of the large amounts of enzymes stored in the pancreas. Moreover, the enzyme content in zymogen granules was below normal values since the stimulatory CCK action on enzyme synthesis can be inhibited by L-364,718. Our results suggest that the efficiency of CCK antagonists, as potential therapy, would also depend on the load of enzymes in the pancreas when acute pancreatitis is produced.

Acute Disease↗

PubMed1999

Zymogen granule alterations in caerulein-induced pancreatitis developed during continuous hydrocortisone administration.

BACKGROUND: The amount of enzymes stored in individual zymogen granules and the glycosylation of their membrane have been analysed in rats with acute pancreatitis induced by caerulein after hydrocortisone treatment. The consequences of prolonging hydrocortisone administration after pancreatitis and the use of the cholecystokinin (CCK) receptor antagonist, L-364,718, have also been evaluated. MATERIALS AND METHODS: Analysis was performed using flow cytometry. RESULTS: Caerulein-induced pancreatitis in rats previously treated for 7 days with hydrocortisone (10 mg kg-1 per day) revealed alterations in enzyme storage in the pancreas. Significant increases in amylase and trypsinogen contents in zymogen granules were observed, an effect associated with a reduction in L-fucose glycoconjugates. Pancreatitis persists 7 days later if hydrocortisone treatment is prolonged. At this stage, a reduced granule fucosylation was still observed, and a significant decrease in the amount of trypsinogen stored in the granules was found. However, hydrocortisone administration led to an increase in intragranular amylase quantities up to normal values, even when L-364,718 was simultaneously administered, but it reverted to plasma as a consequence of pancreatitis. The amount of N-acetyl D-glucosamine in the zymogen granule membrane was not altered by caerulein acute pancreatitis induced under continuous hydrocortisone treatment, but it was decreased by the administration of L-364,718 over 7 days after pancreatitis induction. CONCLUSIONS: The administration of hydrocortisone after the development of pancreatitis prevented recurrence of the disease. L-364,718 proved to be detrimental, not only failing to reduce the symptoms of pancreatitis but also altering the glycoproteins of zymogen granule membrane.

Acetylglucosamine↗

PubMed1998

Effect of cholecystokinin blockade on the recovery of alterations induced by acute pancreatitis in glycoconjugates of rat zymogen granules.

Lectin-binding studies have been performed on rat zymogen granules to investigate alterations in the carbohydrate membrane composition that occur in acute pancreatitis induced by caerulein. The influence of treatment with hydrocortisone for seven days before inducing pancreatitis was also studied. Lectin labeling on zymogen granules was also analyzed seven days after inducing pancreatitis in rats that had previously received a hydrocortisone treatment. During this period L 364,718 (0.1 mg/kg)--specific cholecystokinin (CCK) receptor antagonist--was administered daily to some of the rats, and no treatment was applied to others. Using fluorescein-labelled T. purpureus (TP)lectin, a significant decrease in the amount of L-fucose in the granule membrane was observed in rats with caerulein-induced pancreatitis. This effect was directly caused by the pancreatitis and was not influenced by previous hydrocortisone treatment. Seven days later, the density of TP receptors in the granule membrane was similar to the controls both in L-364,718-treated and untreated rats. Therefore, we suggest that endogenous CCK is not an essential factor in the recovery of L-fucose containing glycoconjugates the granule membrane after pancreatitis. Acute pancreatitis did not alter the expression of wheat germ agglutinin (WGA) receptors in the zymogen granule membrane. WGA specifically binds N-acetyl glucosamine and sialic acids. L 364,718 administered for seven days after inducing pancreatitis significantly reduced WGA binding, untreated rats showed a normal zymogen granule membrane. Therefore, the blockade of CCK-induced alterations in membrane glycoconjugates enriched in N-acetyl glucosamine and sialic acid of newly formed granules after pancreatitis, a finding that could explain the delay in the regression of the disease.

Amylases↗

PubMed1997

Hydrocortisone induces an increase of amylase content in individual zymogen granules from rat pancreas.

This study was performed to evaluate the effects of different doses of hydrocortisone (1, 10 and 25 mg/kg/day) administered for 1, 3 and 8 days on pancreatic enzyme storage in rats. The enzyme content in both pancreas homogenates and in individual isolated zymogen granules (ZGs) was measured using standard biochemical assays and flow cytometry, respectively. Hydrocortisone did not alter the total amount of pancreatic DNA but increased the pancreas enzyme content in a time-dose-dependent way. Amylase activity was significantly increased after hydrocortisone administration at day +8 when 10 mg/kg/day was used, and from the first day of treatment when 25 mg/kg/day was administered. A significant increase in trypsin activity was also observed in response to 25 mg/kg/day of hydrocortisone but only from the third day of treatment onwards. As compared with control rats, chronic administration of either 1 or 10 mg/kg/day of hydrocortisone did not alter significantly either the size or the percentage of the two ZG subpopulations (Z1 and Z2) identified in the pancreas by flow cytometry; in addition, no significant changes were observed in the mean amylase content per individual granule, although its mean concentration increased in rats treated with 10 mg/kg/day for 3 and 8 days. Nevertheless, when 25 mg/kg/day of hydrocortisone were administered for 1 and 3 days, a significant increase in the proportion of Z1 ZGs was observed, which may be related to the formation of new and smaller ZGs. When a very high dose of hydrocortisone (25 mg/kg/day) was used, an overall increase in the pancreatic enzyme content related to an increase in the mean amylase content per individual ZG was observed; this effect was apparent from the first day of treatment in the Z1 subset of ZGs and from day +3 in the Z2 subpopulation. Only a high concentration of hydrocortisone was able to alter the enzyme storage process in individual zymogen granules, but they maintain a normal enzyme load at lower hydrocortisone doses.

Amylases↗

PubMed1995

Adrenalectomy induces a decrease in the light scatter properties and amylase content of isolated zymogen granules from rat pancreas as analyzed by flow cytometry.

The effect of glucocorticoid deprivation induced in male rats by adrenalectomy on the pancreatic zymogen granules was studied. Zymogen granules were purified from control, sham-operated and adrenalectomized animals studied 1, 3 and 7 days after surgery. The zymogen granules were characterized by flow cytometry, and in each granule the size (based on the forward or low angle light scatter (FSC) parameter), membrane complexity (based on side or 90 degrees light scatter (SSC) parameter) and amylase content were evaluated. Amylase content/DNA ratio in pancreatic homogenates was also analyzed. The zymogen granules of the control rats were found to be distributed in two populations: a major one-R1 (95.45 +/- 1.21%)-containing zymogen granules with a smaller mean size and complexity, and a minor population-R2 (4.45 +/- 0.24%)-the granules of which had a mean size which was larger and more complex. At day +1 after adrenalectomy the zymogen granules were significantly (P < 0.05) smaller than those of control animals. The R2 zymogen granules were similar to those from R1 as regards their size, but were more complex, suggesting that the immediate effect of glucocorticoid deprivation is to induce a depletion of the larger granules presumably belonging to the R2 population. The amount of amylase per granule did not vary at day +1 after adrenalectomy, although the amylase content/size ratio per granule was significantly (P < 0.001) increased. This mechanism could be explained in terms of the existence of a bypass defined in the adrenalectomized animals between the granular content and cytosolic enzymes. Prolongation of the adrenalectomy period to 3 and 7 days resulted in a progressive increase in zymogen granule size and complexity, both parameters showing similar characteristics to those of the controls at day +7 after adrenalectomy. However, the percentage of zymogen granules within the R1 and R2 populations was clearly different from that of controls since the R2 population was much more numerous (11.25 +/- 0.75% and 15.25 +/- 1.15% (adrenalectomized rats at days +3 and +7 respectively) versus 4.45 +/- 0.24% (controls)). An increase in the content of amylase per DNA was observed in adrenalectomized rats at day +1 although this transient effect cannot be related to glucocorticoid deprivation because it was also observed in sham-operated rats (day +1). However, a significant reduction, nearly 64%, in the amylase content/DNA ratio is produced by the absence of glucocorticoids 7 days after adrenalectomy and this is associated with a reduction in the content of amylase in each individual zymogen granule which reaches a minimum 3 days after adrenalectomy. It should be noted that, despite this, the enzyme concentration in each granule remains constant as there is a parallel decrease in the zymogen granule amylase content and size.

Adrenalectomy↗

PubMed1995

Effects of the cholecystokinin receptor antagonist L-364,718 on pancreatitis induced by a deficient in choline and supplemented with ethionine (CDE) diet in the rat.

The role of cholecystokinin (CCK) in the development of a necrotizing acute pancreatitis induced by a diet deficient in choline and supplemented with ethionine (CDE) has been evaluated in the rat by using a potent CCK receptor antagonist L-364,718. Acute pancreatitis was induced by administration of CDE diet for 14 days. L-364,718 administration was carried out by subcutaneous injections at dose of 0.1 mg/kg/day. Pancreatic exocrine secretion (flow, protein, amylase and trypsin outputs) in resting and under infusion of 1.25 microgram/kg/h of CCK-8 were used to evaluate the pancreatic functionality. Others parameters (serum amylase, percentage fluid in pancreas, haematocrit and mortality) evaluated the severity of pancreatitis. L-364,718 slightly reduced the mortality and the increases of percentage of fluid accumulated in pancreas in CDE diet acute pancreatitis. Basal and CCK stimulated pancreatic secretion was significantly depressed 36 hours after L-364,718 treatment. A slight response to CCK was observed. Nevertheless it was lower than usually observed in control rats. Our results demonstrate that in the rat, chronic L-364,718 treatment did not completely restore pancreatic activity in acute pancreatitis induced by CDE diet. Hence CCK cannot be considered as the main factor involved in the development of this pancreatitis model.

Acute Disease↗

PubMed1995

Dose-response effects of VIP on the rabbit exocrine pancreatic secretion. Comparison with PACAP-27 actions.

A dose-response study of the effects of vasoactive intestinal peptide (VIP) on the exocrine pancreatic secretion of the rabbit has been made. Furthermore, the actions of VIP and pituitary adenylate cyclase activating peptide (PACAP) on the exocrine pancreatic secretion were compared at a similar molar dose. After the infusion of VIP a linear dose-response relationship for pancreatic flow rate and bicarbonate output, up to the dose of 4 micrograms/kg, was observed. VIP acts as a partial agonist of secretin, the rabbit pancreas being less sensitive to VIP compared with other mammals. Moreover, VIP did not significantly stimulate the pancreatic protein output. PACAP stimulated the hydroelectrolyte fraction of the exocrine pancreatic secretion in a similar manner to that of VIP. Unlike what was observed with VIP, PACAP, on the same molar basis, significantly stimulated the protein and amylase outputs. Furthermore, PACAP releases VIP, so that the action of PACAP on the hydroelectrolyte fraction may be partially mediated by VIP; on the other hand, VIP is not involved in the effect of PACAP on the pancreatic enzyme secretion of this species.

Amylases↗

PubMed1994

Effect of L-364,718 (CCK receptor antagonist) on exocrine pancreatic secretion of hydrocortisone-treated rats.

Exocrine pancreatic function was studied in control rats and animals subjected to treatment with hydrocortisone (10 mg/kg/day) over 7 days. In both cases, the cholecystokinin (CCK) receptor antagonist L-364,718 (0.1 mg/kg/day) had been administered. The administration of this nonpeptide CCK antagonist significantly reduced the basal pancreatic flow of secretion and enzymes in the control rats but did not cause a decrease in pancreatic weight. From this it may be inferred that factors other than CCK are able to exert the trophic effects of this hormone. Also, the processes of enzyme synthesis and storage, which contribute to maintaining the weight of the organ, continued to occur under conditions of deprivation of the action of endogenous CCK because pancreatic secretion in response to the infusion of CCK was similar in the animals treated and not treated with L-364,718. In contrast, no significant changes were observed either regarding pancreatic weight or basal pancreatic secretion in the animals treated with hydrocortisone and simultaneously with L-364,718, as compared with the rats treated only with hydrocortisone. This points to a predominant effect of glucocorticoids on the action of CCK during the phases of enzyme synthesis and storage, accompanied by a blockade of exocytosis due to hydrocortisone treatment. The secretagogue effect of CCK alone becomes possible with high levels of this hormone of exogenous origin, whose interaction with its specific receptors is in turn positively modulated by an excess of glucocorticoids.

Amylases↗

PubMed1994

Therapeutic and protective effect of subcutaneous injections of L-364,718 on caerulein-induced acute pancreatitis.

The prophylactic and therapeutic effects of a potent cholecystokinin (CCK) receptor antagonist, L-364,718, on acute pancreatitis induced by caerulein were evaluated, analyzing morphologic and functional pancreatic parameters jointly. Edematous pancreatitis was induced by four subcutaneous injections of caerulein (20 micrograms/kg) in rats at 1-h intervals. Prophylactic administration of L-364,718 (0.1 mg/kg) prevented rise in serum amylase levels, interstitial edema, vacuolization, and impairment of pancreatic enzyme secretion that accompany caerulein-induced acute pancreatitis. After 7 days, a spontaneous regression of the morphologic alterations caused by caerulein-induced acute pancreatitis occurs; however, recovery of the secretory function of the pancreas was only reached after this period of time when L-364,718 was administered therapeutically (0.1 mg/kg/day). Prophylactically or therapeutically administered, L-364,718 exerts a beneficial effect on caerulein-induced acute pancreatitis, indicating that CCK (exogenous or endogenous) plays an important role in the development of this pathology.

Acute Disease↗

PubMed1993

Exocrine pancreatic response to intraduodenal fatty acids and fats in rabbits.

1. The exocrine pancreatic secretion in rabbits after intraduodenal perfusion of, respectively, a short-chain fatty acid (propionate), a long-chain fatty acid (oleate) and a neutral fat (intralipid) has been studied. 2. Only the neutral fat and the long-chain fatty acid stimulated the hydroelectrolyte fraction of exocrine pancreatic secretion in a dose-related fashion, but this response was not mediated by secretin release. 3. Acinar secretion was more effectively stimulated after propionate perfusion than by oleate and this was governed by different mechanisms. 4. Neutral fat, without predigestion, stimulated the pancreatic enzyme secretion in the rabbit.

Animals↗

PubMed1993

Effect of L-364,718 (CCK receptor antagonist) on exocrine pancreatic secretion of adrenalectomized rats.

The exocrine pancreatic secretion of control and adrenalectomized rats treated with L-364,718 was studied. The blockade of the action of endogenous cholecystokinin (CCK) in the control animals was reflected in a reduction of basal pancreatic secretion. This effect was reversed by the administration of submaximal doses of CCK-8. Under treatment with L-364,718, no decrease in pancreatic weight was observed. From this it may be deduced that factors other than CCK act on the pancreas to maintain the processes of enzyme synthesis and storage. Adrenalectomy reduced the weight of the pancreata; the main cause of this was the depletion of zymogen granules, which has been reported in adrenalectomized rats and is accompanied by a reduction in enzyme secretion, especially that of amylase. By contrast, the administration of L-364,718 from the very first moments after adrenalectomy leads to a retention of pancreatic enzymes. This effect is reflected in the maintenance of pancreatic weight and a secretory capacity in response to submaximal doses of CCK-8 similar to that of nonadrenalectomized animals. Accordingly, in the absence of glucocorticoids, endogenous CCK dominates the secretory process because when the action of this secretagogue is prevented by the administration of L-364,718, the discharge of proteins able to be secreted in response to a suitable stimulus is inhibited.

Adrenalectomy↗

PubMed1990

Acinar cholecystokinin (CCK) receptors in the exocrine pancreas of the rat: effect of adrenalectomy.

The binding of [125I]BH-CCK-8 to membranes of acinar cells from rats at 6 and 21 days after adrenalectomy was studied. The optimum conditions of time and temperature were previously established as being 120 min and 30 degrees C. Under these conditions, the membranes of the adrenalectomized animals of both groups (6 and 21 days) bound more radioligand than those from control rats. However, a qualitative study of the binding showed that the affinities of binding were much lower; in particular, the high affinity receptors had a Kd of 0.94 +/- 0.33 nM in the controls and this was 14.9 +/- 1.29 nM in the 6-day adrenalectomized animals, although the maximum binding capacity did not vary significantly. However, in the case of the low affinity receptors, there was a gradual increase in the maximum binding capacity as the time after adrenalectomy progressed: 717 +/- 121, 1,987 +/- 183, and 10,175 +/- 862 fmol/mg for the control, 6-day, and 21-day adrenalectomized rats, respectively. In the latter situation, the high affinity receptors completely disappeared. These results, which coincide with a marked deficit in protein secretion already described in adrenalectomized rats, can be accounted for in terms of the possible negative cooperativity exerted by the low affinity receptors on the high affinity hormone-receptor complex, the protein secretion of the acinar cells normally mediated by the high affinity receptors becoming paralyzed.

Adrenalectomy↗

PubMed1990

Caerulein-induced acute pancreatitis in the rat. Pancreatic secretory response to cholecystokinin.

The response of pancreatic exocrine secretion to cholecystokinin (CCK), has been studied in experimental acute pancreatitis induced in rats by supramaximal doses of caerulein. Several doses of caerulein were used (4, 20 and 40 micrograms/Kg) and each one was administered by four subcutaneous injections over 3 h at hourly intervals. Pancreatic juice was collected 9 h after the first injection. The caerulein-treated animals showed a statistically significant increase in serum amylase levels. Secretory activity of ductular cells remained unchanged in all the caerulein-treated animals, but total protein and amylase secretion decreased significantly at all the caerulein doses used, both in resting conditions and under stimulation with CCK (1.25 micrograms/Kg/h). Despite this the acinar cells of rats treated with the lowest dose of caerulein retained a certain degree of secretory function since amylase activity in pancreatic juice was greater than in other groups of rats treated with higher doses of caerulein. Moreover, the percentage of increase observed in total protein and amylase in response to CCK respect to basal secretion is similar to that of the untreated animals. At higher doses (20 and 40 micrograms/Kg) the secretory capacity in response to CCK was inhibited. Therefore CCK administration in slight acute pancreatitis could be used as a therapy since it favours the secretion of pancreatic enzymes at percentual levels similar to those of the controls.

Acute Disease↗

PubMed1989

Beta 1 and beta 2 adrenergic agonists in exocrine pancreatic secretion in the rabbit.

The effect of Dobutamine (a beta 1-adrenergic agonist) and Terbutaline (a beta 2-adrenergic agonist) on exocrine pancreatic secretion was studied in anaesthetized rabbits, simultaneously controlling pancreatic blood flow and blood pressure. The secretion of fluid and ions (bicarbonate, sodium and potassium) was unaffected by the infusion of Dobutamine (8 micrograms.kg-1.min-1) or Terbutaline (10 micrograms.kg-1.min-1). Neither were pancreatic blood flow or mean blood pressure altered. Dobutamine or Terbutaline depress the function of the acinar cells, amylase secretion being more affected by the action of Terbutaline. The results show that beta 1 and beta 2-adrenergic stimulation has no effect on the ductular cells but does decrease the secretion by the acinar cells.

Adrenergic beta-Agonists↗

PubMed1989

Exocrine pancreatic response to isoproterenol in the rabbit under secretin and CCK stimulation.

The effect of isoproterenol (0.3 micrograms/Kg/min) on exocrine pancreatic secretion stimulated by secretin (1. C.U./Kg/h) and the octapeptide of cholecystokinin (OP-CCK 0.15 Ivy dog units/Kg/h) was studied in anaesthetized rabbits. Pancreatic blood flow remained unaffected by the action of isoproterenol; however, the administration of the beta-adrenergic agonist over an infusion of secretion an OP-CCK led to an increase in pancreatic juice flow (approximately 146% for secretin and 125% for OP-CCK) and HCO3-output (approximately 194% for secretin and 150% for OP-CCK), a potentiation being observed between the effects of secretin and isoproterenol. This kind of response, independent of vascular changes, is due to a direct action of isoproterenol on the ductular cells. Isoproterenol interferes with the action of secretin and OP-CCK in that it partially inhibits the stimulatory action of OP-CCK on the enzymatic secretion of the acinar cells in the rabbit pancreas and at the same time protein secretion decreases in the presence of secretin.

Acid-Base Equilibrium↗