Biomedical subjects

M Papp

Publications and source records attributed to M Papp.

At least 73 records · Page 4Linked to original sources

PubMed1990

Cholinergic and adrenergic control of enzyme secretion in isolated rat pancreas.

While cholinergic nervous control of pancreatic enzyme secretion is well documented, data concerning adrenergic regulation of the exocrine pancreas are contradictory. In the present study we attempted to elucidate the direct action of adrenergic stimulation on pancreatic enzyme secretion. Rat pancreatic segments were set up in an organ bath and superfused with modified Krebs-Henseleit solution. Electrical field stimulation (EFS) stimulated amylase release from the segments. This stimulation was subject to inhibition with atropine up to 80%. Atropine-resistant enzyme discharge in response to EFS could be blocked by propranolol. Cholinergic agonist urecholine-induced amylase release was completely blocked by atropine. Noradrenaline (NA) exhibited a biphasic effect on amylase release. It inhibited the urecholine-induced amylase release in lower concentrations (10(-8)-10(-7) M), while it stimulated basal enzyme secretion in higher concentrations (10(-5)-10(-4) M). The inhibitory effect was mimicked by phenylephrine and completely prevented by prazosin. Isoprenaline concentration dependently enhanced, while clonidine and guanfacine did not affect amylase discharge. In conclusion, in rat pancreatic acinar tissue it seems likely that acetylcholine is the main neurotransmitter. Adrenergic action can be dual, inhibitory via alpha 1-adrenoceptors or stimulatory via beta-adrenoceptors on amylase secretion.

Amylases↗

PubMed1990

Pimozide does not impair sweetness discrimination.

In an initial experiment pimozide decreased preference for a weak sucrose solution but increased preference for a strong solution on the descending limb of the concentration-intake function. As these effects resemble those of dilution, we therefore investigated whether pimozide decreases the perceived intensity of sweet stimuli. Rats were trained to perform a conditional discrimination in a T-maze. A correct response was rewarded by access to a 10% sucrose solution; an incorrect response was punished by confinement in the non-rewarded arm. In the first part of this experiment the discriminative stimulus, located at the choice point of the T-maze, was either water or sucrose, initially a 10% solution, but reduced gradually to 0.0003%. In the second part of the experiment, the discriminative stimulus was either 1% sucrose or a weaker solution, which was initially 0.0001% then raised gradually to 0.5%. Performance fell below 75% accuracy at 0 versus 0.0012% and at 1% versus 0.1%. Pimozide (0.5 mg/kg) administered at these (and other) levels of difficulty decreased running speed but had no effect on discrimination accuracy. As pimozide did not affect either the threshold for sweetness perception or the discrimination of a just noticeable difference, the decreased responsiveness of neuroleptic-treated rats to sweet rewards cannot be explained by a change in the perception of sweetness.

Animals↗

PubMed1990

Secretin potentiates, caffeine does not affect caerulein--stimulated pancreatic enzyme depletion and growth in newborn rats.

We studied the effect of two peptides, the intracellular Ca2(+)-mobilizing caerulein and the cAMP-mediated secretin, and also the phosphodiesterase inhibitor caffeine on pancreatic secretion and growth in newborn rats. To investigate the secretory response of these substances, and to construct dose-response curves 10-day-old conscious rats were given subcutaneously a single injection of caerulein, secretin, caffeine or the combination of these compounds (caerulein + secretin, caerulein + caffeine). Fifteen min after the injection pancreatic specific trypsin activities were measured in order to estimate depletion of enzymes from the pancreas. To study the pancreatic growth--promoting effect of these substances, newborn rats were treated three times daily for 10 days from the day of birth, using the same experimental groups as described above. Caerulein stimulated both enzyme depletion and pancreatic growth. Secretin stimulated enzyme depletion and increased the trophic effects of caerulein on the pancreas. Caffeine alone or in combination with caerulein did not affect pancreatic enzyme depletion and growth.

Amylases↗

PubMed1990

Bombesin-induced pancreatic secretion and growth in rats: effect of proglumide, spantide and ranitidine.

The effect of proglumide (400 mg/kg), spantide (400 g/kg) and ranitidine (20 mg/kg) on pancreatic secretory and trophic response to bombesin (10 micrograms/kg) was studied in the rat. Drugs were administered alone or combined with bombesin three times daily for 5 days. Saline-treated rats were used as controls. At the end of treatment, animals were anaesthetized and pancreatic juice was collected for 1 h after caerulein stimulation (1 microgram/kg intraperitoneally). Afterwards, rats were sacrificed and the weight and composition of pancreatic tissue were determined. As compared with control (saline) values, the volume of pancreatic juice and the output of trypsin and amylase were increased by treatment with bombesin. Neither proglumide nor spantide affected basal and caerulein-stimulated pancreatic exocrine secretion. Ranitidine, although unable to modify protein and enzyme content of pancreatic secretion, significantly reduced the volume of pancreatic juice in both basal conditions and after caerulein stimulation. Bombesin increased pancreatic weight as well as the protein and enzymatic contents of the gland. Neither the weight of the pancreas nor its composition were significantly affected by CCK-antagonist proglumide, the putative bombesin antagonist spantide or the H2-receptor antagonist ranitidine. These results show that bombesin has a trophic effect on rat pancreas and concomitantly increases its secretory capacity. Both effects are likely to be mediated through a direct action of the peptide on the pancreatic gland.

Animals↗

PubMed1989

[The effect of somatostatin on pancreatic enzyme secretion in rats in vivo and in vitro].

Authors investigated the inhibitory effect of somatostatin on pancreatic enzyme secretion in vivo and in vitro, in rats. In conscious animals somatostatin strongly inhibited pancreatic amylase secretion. In vitro, however, amylase secretion was not affected by the peptide: it had no affect either on basal secretion, or on stimulated secretion induced via CCK-, or cholinergic receptors. Furthermore, it did not modify nerve-stimulation induced enzyme secretion. The results suggest that the in vivo inhibitory action somatostatin on pancreatic enzyme secretion is an indirect one.

Amylases↗

PubMed1989

The influence of repeated treatment with imipramine, (+)- and (-)-oxaprotiline on behavioural effects of dopamine D-1 and D-2 agonists.

The paper examined the action of imipramine, (+)- and (-)-oxaprotiline, administered repeatedly to rats, on the behavioural effects of the dopamine D-1 and D-2 agonists, SKF 38393 and quinpirole, respectively. The three antidepressants studied, given in the single dose or repeatedly, attenuate the enhanced grooming evoked by SKF 38393. The locomotor hyperactivity, evoked by quinpirole administered s.c., is increased by repeated but not single-dose treatment with imipramine and (+)-oxaprotiline [but not with (-)-oxaprotiline]. Quinpirole at a low dose produces the locomotor hypoactivity which is attenuated by repeated, but not single-dose, treatment with the anti-depressants studied here. Repeated imipramine and (+)-oxaprotiline [but not (-)-oxaprotiline] increase the locomotor activity effect of quinpirole injected into the nucleus accumbens. The results indicate that the enhanced responsiveness of the dopamine system, observed previously after repeated treatment with antidepressants, may be mediated by the dopamine D-2 receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1989

Caerulein stimulates pancreatic secretory response in conscious newborn rats.

UNLABELLED: The aim of our study was to measure age-dependent, caerulein-stimulated pancreatic enzyme secretion of conscious CFY suckling rats without pancreatic duct cannulation. Pancreatic secretory response was expressed as the decrease in specific enzyme (trypsin, amylase) activity compared to saline-injected control. The study was performed in three phases. In 10-d-old conscious newborn rats, single 1 and 3 micrograms/kg sc doses of caerulein induced significant decreases in specific trypsin (42 and 47%) and amylase (34 and 33%) activity 15 min after the caerulein injection; the same doses injected at 0 and 30 min evoked a similar decrease 90 min after the first injection. The 0.5 microgram/kg dose was ineffective. In 10-d-old anesthetized rats, the 90-min-decrease in total pancreatic trypsin activity, induced by graded doses (1,3,10, and 30 micrograms/kg) of caerulein, was compared to the 90-min output of trypsin in their bile-pancreatic juice. Each of the applied doses induced significant change in the total trypsin activity both in the pancreas (-33-57%) and juice (+21 +/- 49%) and its decrease in the gland corresponded quantitatively well (r = 0.52; p less than 0.01) to the increase in the simultaneous 90-min trypsin output. The age- and dose-dependent pancreatic response of 3-, 5-, 10-, and 20-d-old conscious rats was investigated under the effect of 1,3,10, and 30 micrograms/kg sc doses of caerulein injected at 0 and 30 min. In 3-d-old rats, the 10 and 30 micrograms/kg and in 20-d-old rats, the 1 and 3 micrograms/kg doses were effective, whereas in 5- and 10-d-old rats each caerulein dose applied evoked a significant decrease in pancreatic-specific trypsin activity. CONCLUSION: The pancreas of newborn rats is in vivo less sensitive to caerulein between postnatal d 3 and 10 than in already weaned rats.

Aging↗

PubMed1989

Pancreatic secretory and trophic response to caerulein in rats: effect of proglumide and lorglumide.

The effect of proglumide and lorglumide, two CCK-receptor antagonists, on caerulein-induced pancreatic secretion and growth was studied in the rat. In anaesthetised animals, caerulein (1 microgram/kg) significantly increased the volume of pancreatic juice and protein output. Lorglumide (5 and 10 mg/kg), administered intraperitoneally 15 min before stimulation, reduced peptide-induced pancreatic exocrine secretion. By contrast, proglumide (100 and 400 mg/kg) was completely ineffective. In experiments dealing with the trophic effect of caerulein, both drugs were administered alone or combined with the peptide (1 microgram/kg) 3 times daily for 5 d. Saline-treated rats served as controls. At the end of the experiment, rats were sacrificed, and growth and composition of pancreatic tissue were determined. Pretreatment of the animals with either proglumide or lorglumide did not affect pancreatic size and composition. Caerulein increased the weight of the pancreas, the total pancreatic protein, trypsin, amylase, and DNA content. After pretreatment with proglumide, all these parameters were not significantly different from those obtained with caerulein alone. In contrast, when lorglumide was given together with caerulein, it significantly reduced caerulein-induced pancreatic growth and decreased enzymatic protein content of the gland. These results show that lorglumide is a much more potent and effective CCK-receptor antagonist than proglumide. Its ability to antagonize the pancreatic secretory and trophic action of a CCK-analogue (i.e. caerulein) supports the view that these physiological actions of CCK are mediated through an interaction of the hormone with specific receptors.

Amylases↗

PubMed1989

Effect of a new potent CCK antagonist, lorglumide, on caerulein- and bombesin-induced pancreatic secretion and growth in the rat.

1. The effect of lorglumide, a new potent cholecystokinin (CCK) antagonist, on pancreatic secretion and growth induced by caerulein and bombesin was studied in the rat. 2. Pancreatic exocrine secretion was studied both in vitro (isolated and perfused pancreatic segments) and in vivo (anaesthetized animals with cannulation of the common bile duct) whereas the trophic effect was investigated after short-term (5 days) administration of the peptides and/or lorglumide. 3. Both caerulein and bombesin stimulated amylase release from in vitro pancreatic segments in a concentration-dependent manner. Although the efficacy of both peptides was virtually identical, the potency of caerulein was higher than that of bombesin. Lorglumide displaced the concentration-response curves to caerulein to the right without affecting the maximum response, suggesting a competitive antagonism. The Schild plot analysis of data gave a straight line with a slope not significantly different from unity. The calculated pA2 for lorglumide was 7.31 +/- 0.45. The antagonist, however, was completely ineffective when tested against bombesin-induced amylase release. 4. In vivo experiments confirmed results from in vitro studies since lorglumide (5 and 10 mg kg-1) significantly reduced pancreatic exocrine secretion induced by caerulein without affecting the response to bombesin. 5. Administration of either peptide increased the weight of the pancreas, the total pancreatic protein and DNA, trypsin and amylase content. Lorglumide (10 mg kg-1), administered together with caerulein, reduced the peptide-induced increase in pancreatic weight, protein and enzyme content. On the contrary, when lorglumide was given together with bombesin, all the parameters that were examined were not altered by concomitant administration of the antagonist. 6. These results have demonstrated the ability of lorglumide to antagonize the effects on the pancreas of a CCK-analogue, caerulein, and its inability to affect bombesin-induced pancreatic secretion and growth, suggesting that lorglumide is a potent and selective antagonist of CCK-receptors in the pancreas.

Amylases↗

PubMed1989

Time-specific development of pancreatic hypersecretory capacity during chronic caerulein treatment in rats.

It is well established that repeated injections of the cholecystokinin (CCK) analogue caerulein induce pancreatic hypersecretion and growth, but so far the time-specific development of hypersecretory capacity has not been studied. Rats were given intraperitoneal injections of caerulein (1 microgram/kg) three times daily for 0-7 days. On the day after the last injection a secretory test was performed with the rats under urethane anaesthesia. Subsequently, pancreatic tissue composition was analysed. Basal and caerulein-stimulated secretion rates of fluid and trypsin were elevated after as little as 1 day of caerulein treatment. These values remained significantly greater than those of the controls after 2-7 days' administration of the peptide. Pancreatic tissue hypertrophy (increases in absolute pancreatic weight, protein and trypsin contents, and also in these values normalized to DNA) appeared after 2 days' pretreatment. Tissue growth turned to hyperplasia (increase in tissue DNA content) after 5 days' caerulein administration. We conclude that chronic administration of the CCK analogue caerulein induces adaptation of the pancreas in a sequential order. First, the hypersecretory state appears, followed by hypertrophy, and, finally, pancreatic growth turns into hyperplasia.

Animals↗

PubMed1989

Activity of "nonspecific pancreatic carboxylesterase" in rat serum in experimentally induced acute pancreatitis (preliminary results).

The aim of this study was to obtain more information on the serum level of "nonspecific pancreatic carboxylesterase" (PCE) in experimentally induced acute pancreatitis in rats. The effects of caerulein stimulation, hepatic duct ligation, bile-pancreatic duct ligation or the effect of retrograde injection of saline, 5% taurocholate and sunflower oil were investigated. The activity of PCE and amylase was measured in the serum, pancreatic tissue, pancreatic juice and ascitic fluid. The changes in PCE activity were greater (both in directions to increase or decrease) than that of amylase, produced by different experimental procedures. The results confirm the thesis that the serum activity of PCE is a more sensitive diagnostic method than that of amylase to detect the inflammatory process in the pancreas or the effect of obstruction of the pancreatic duct.

Acute Disease↗

PubMed1989

Effects of some gastrointestinal peptides on pancreatic growth in rats (preliminary results).

The purpose of this study was to estimate the effects of cholecystokinin (CCK), somatostatin (SS) pancreatic polypeptide (PP) and their interaction with each other, given them in single doses, on pancreatic secretion and pancreatic growth after long-term treatment in rats. The acute secretory effects of the above mentioned peptides were studied on conscious rats supplied with pancreatic, gastric and jugular vein cannulae. The pancreatic growth was characterized by measurements of pancreatic weight, desoxyribonucleic acid (DNA), protein, trypsin and amylase content after 5 days treatment. Amylase output was increased by caerulein alone, and given it in combination with somatostatin (SS), while its value decreased by SS alone. After 5 days treatment, the pancreatic weight, trypsin and amylase activity (hypertrophy) was increased by caerulein, and these values were not altered by S alone. In combinative administration of caerulein with somatostatin, the stimulatory effect by caerulein was decreased. PP given alone or in combination with caerulein decreased both the basal and stimulated amylase output. PP given for 5 days decreased pancreatic trypsin and amylase contents and counteracted the stimulatory effect by caerulein to these enzymes' contents. It has been concluded that: 1. caerulein stimulates both pancreatic enzyme secretion and pancreatic growth; 2. somatostatin inhibits the pancreatic secretion and caerulein induced pancreatic growth, but it does not affect the spontaneous growth of pancreas; 3. pancreatic polypeptide inhibits the pancreatic secretion and decreases pancreatic trypsin and amylase contents.

Amylases↗

PubMed1989

Caerulein-induced desensitization of enzyme secretion fails in neonatal rat pancreas.

Pancreatic segments of 1-, 3-, 5-, 10-day-old and adult female OFA (Sprague-Dowley strain) rats were superfused with graded concentrations of caerulein (10(-12)-10(-7) M) to establish concentration-response relation of amylase release. Furthermore, pancreatic segments of 3-, 5-, 10-day-old and adult rats were superfused with 10(-10) or 10(-8) M caerulein and then superfusion was repeated with 10(-10) M concentration of caerulein to show whether the phenomenon of desensitization of amylase release can be induced in the postnatal period. The 1-day-old pancreas was found practically insensitive to caerulein. The 3- and 5-day-old gland was by one order of magnitude less sensitive (EDmax = 10(-8) M) than the adult pancreas (EDmax = 10(-9) M). Repeated superfusion of the 3- and 5-day-old pancreas with 10(-10) M caerulein after the first 10(-8) M caerulein superfusion failed to cause desensitization, while the same (10(-10) M) repeated superfusion of the 10-day-old adult pancreatic segments after the first 10(-8) M caerulein superfusion evoked desensitization of enzyme release. The authors suggest that the failure of desensitization of enzyme secretion for caerulein may be due to the maturation process of newborn rat pancreatic acinar cells at receptorial and postreceptorial level.

Aging↗

PubMed1989

Effect of treatment with submaximal and excessive doses of caerulein on pancreatic growth in newborn rats.

Different groups of CFY female newborn rats were treated with saline, or 1 microgram/kg or 100 micrograms/kg doses of caerulein given s. c. 3 x/day. Application of 100 micrograms/kg dose of caerulein for 3 days stimulated pancreatic growth inducing pancreatic hyperplasia; both (1 and 100 micrograms/kg) doses evoked increase in trypsin/DNA ratio inducing pancreatic hypertrophy in 4-days-old rats. Using the indices as before application of 1 microgram/kg caerulein for 10 days stimulated pancreatic growth and both (1 and 100 micrograms/kg) doses elicited glandular hypertrophy in 11-days-old rats. In 24-old-rats the 1 microgram/kg doses of caerulein given for 3 days stimulated pancreatic growth and induced pancreatic hypertrophy, the 100 micrograms/kg doses of the peptide given for 3 days, however, evoked pancreatic aplasia and atrophy.

Animals↗

PubMed1989

The pancreas and oxygen consumption (Part 2). Steroids do not modify resting pancreatic oxygen consumption in dogs: a preliminary report.

In order to evaluate the effect of methylprednisolone sodium succinate (MPSS) on the alteration of pancreatic oxygen consumption (VO2) in hypovolemic shock, MPSS was administered to four normal canines and three hypovolemic animals. All were treated according to the protocol used in the initial report. (The Pancreas and Oxygen Consumption 1: Pancreatic Oxygen Consumption in Normo- and Hypovolemic Dogs.) All seven underwent a splenectomy at the beginning of the experiment. Pancreatic VO2, obtained by adding up VO2 for the head (minus the uncinate process) and tail of the pancreas, was equal to the product of regional blood flow, Q, determined electromagnetically on the gastroduodenal (GDA) and splenic (SA) arteries, times O2 extraction, (a-v)O2; O2 content (in mL%) was measured in the femoral artery (RFA), in the splenic (SV) and superior pancreaticoduodenal (SPDV) veins. Similar determinations were carried out on the right hind limb that served as a control. Recordings were made for 4 h in both groups, the first hour determinations (five in all) serving as reference values. Methylprednisolone did not appear to alter pancreatic VO2, which showed a significant increasing trend from + 77% 1 h after MPSS had been given, to + 98% 3 h later (vs + 56 and + 92%, respectively, in the control group). As in the control group, these increases were owing to augmented O2 extraction by the pancreas. No significant change was noted between the head and tail of the pancreas. In the hind limb, VO2 increased significantly the first 2 h and differed from control VO2 at the end of the first hour only.

Animals↗

PubMed1989

Pancreatic cytoprotection: a survey.

The author gives a brief survey on the concept of cytoprotection, the generation of prostaglandins and the mechanism of their action. The effect of exogenous prostaglandins and the mechanism of their action. The effect of exogenous prostaglandins on pancreatic vasculature, secretion, ductal permeability and their therapeutic effect on experimentally induced acute pancreatitis is discussed. Pancreatic "self-defence" mechanism is also discussed the mechanism of which may be rather different from that of cytoprotection. In such pancreatic "self-defense" mechanism decrease in pancreatic protein synthesis and secretion induced by pancreatic duct ligation or decrease in sensibility of pancreatic acinar cells or their receptors against specific stimulants may participate.

Animals↗

PubMed1989

The pancreas and oxygen consumption. 1. Pancreatic oxygen consumption in normo- and hypovolemic dogs.

Pancreatic oxygen consumption (VO2) was studied in hypovolemic shock: 4 dogs served as controls and 4 others were kept at 50 mm Hg of mean arterial blood pressure. All 8 were studied for a period of 3 h. Pancreatic VO2 was obtained by adding up VO2 for the head (minus the uncinate process) and tail of the pancreas both equal to the product of regional blood flow times O2 extraction. Regional blood flows were measured electromagnetically on the gastroduodenal (GDA) and the splenic (SA) arteries, whereas O2 extraction was derived from total hemoglobin (THb) and oxygen saturation of hemoglobin (%O2 Hb) determined on the right femoral artery (RFA), the superior pancreaticoduodenal (SPDV), and splenic (SV) veins. A splenectomy was performed in all 8 dogs. Controls showed a significantly elevated pancreatic VO2 from the first hour of observation on (+56% after 1 h, +92% after 3), whereas pancreatic VO2 remained strictly unchanged throughout shock (+2% and +6%, at one and 3 h, respectively), despite significant increases in O2 extraction. These findings give support to the deleterious effects of hypovolemia to the pancreas and that pancreatic O2 extraction indicates metabolic damage to be less severe than observed in experimental bile-trypsin-induced acute pancreatitis.

Acute Disease↗

PubMed1988

Similar effects of diazepam and the 5-HT3 receptor antagonist ICS 205-930 on place aversion conditioning.

The anti-anxiety effect of diazepam and the antagonist of 5-HT3 receptors, ICS 205-930, was studied with a conditioned place aversion test design. The results showed that when one of two distinctive and previously preferred compartments was associated with an inescapable footshock, the control animals avoided that compartment in the post-conditioning test. Both diazepam (1-4 mg/kg i.p.) and ICS 205-930 (0.125-1.0 mg/kg i.p.), given before the post-conditioning test, increased in a dose-dependent manner the amount of time spent by the animals in the compartment conditioned to footshock. The results support the view that central 5-HT3 receptors may be involved in the control of anxiety.

Animals↗