Role of nonesterified fatty acids in necrotizing pancreatitis: an in vivo experimental study in rats.

Introduction: In acute pancreatitis, nonesterified fatty acids (NEFA) might be released by lipase and cause tissue necrosis by their detergent properties, but this has not been established in vivo.

Aims: To measure the release of NEFA in the blood stream, pancreatic tissue, and peritoneal cavity during taurocholate-induced acute necrotizing pancreatitis in rats.

Methodology: Ascites and blood were repeatedly sampled; after 24 hours, pancreatic lesions were scored, and NEFA were measured in the pancreas.

Caseinomacropeptide specifically stimulates exocrine pancreatic secretion in the anesthetized rat.

The effect of caseinomacropeptide (CMP) (the [106-169] fragment of kappa-casein produced during digestion of milk protein), was studied in anesthetized rats using bile diversion for a pure pancreatic juice collection system. Intraduodenal administration of CMP induced a dose-related specific stimulation of pancreatic secretion which was nearly abolished by devazepide, atropine, hexamethonium, vagotomy or perivagal capsaicin pretreatment. Moreover, CMP did not inhibit in vitro trypsin activity.

Oxyntomodulin inhibits pancreatic secretion through the nervous system in rats.

Glicentin (GLIC), oxyntomodulin (OXM), and peptide YY (PYY) released in blood by ileocolonic L-cells after meals may inhibit pancreatic secretion. Whereas OXM interacts with glucagon and tGLP-1 receptors, OXM 19-37, a biologically active fragment, does not. The purpose of this study was to measure the effect of OXM, OXM 19-37, GLIC, tGLP-1, and PYY on pancreatic secretion stimulated by 2 deoxyglucose (2DG), electrical stimulation of the vagus nerves (VES), acetylcholine and cholecystokinin octapeptide (CCK8) in anesthetized rats.

Neural mechanism of the antisecretory effect of peptide YY in the rat colon in vivo.

The purpose of this work was to determine the mechanism of the antisecretory effect of peptide YY in the rat colon and whether this effect is physiological. In this prospect, doses of exogenous peptide YY producing physiological and supraphysiological plasma levels were intravenously infused in rats provided with colonic and jejunal ligated loops in vivo, under secretory stimulation by vasoactive intestinal peptide. Peptide YY decreased the secretory effect of VIP in a dose-related fashion.

Antisecretory effect of peptide YY through neural receptors in the rat jejunum in vitro.

Basal short circuit current (Isc) was measured in stripped rat jejunum after addition of neural antagonists and of peptide YY (PYY). Basal Isc was slightly (by 10-21%) but significantly inhibited by tetrodotoxin, hexamethonium, idazoxan, and the sigma antagonist BMY 14,802. PYY (10(-7) M) reduced basal Isc by approximately 54%.

Cerium-based histochemical demonstration of oxidative stress in taurocholate-induced acute pancreatitis in rats. A confocal laser scanning microscopic study.

Direct in vivo histological detection of oxygen-derived free radicals (OFRs) in inflammatory conditions is not fully resolved. We report an application of cerium histochemistry (in which capture of OFRs by Ce atoms results in laser-reflectant cerium-perhydroxide precipitates) combined with reflectance confocal laser scanning microscopy (CLSM) to demonstrate the evolution of oxidative stress in taurocholate-induced acute pancreatitis (AP) in rats. Animals were perfused with CeCl(3) in vivo and cryostat sections of pancreata were studied by CLSM.

Effect of sumatriptan on external pancreatic secretion and its interaction with endogenous norepinephrine in the rat.

We reported previously that blocking norepinephrine reuptake by nisoxetine could modulate external pancreatic secretion in the rat. We report in this study the interaction of serotonin (5-HT) with endogenous catecholamines by using sumatriptan, an agonist of 5-HT1 receptors, in combination with nisoxetine. Urethane-anesthetized male Wistar rats were fitted with an acute pancreatic fistula.

Comparison of the postprandial release of peptide YY and proglucagon-derived peptides in the rat.

Endocrine L-cells of the distal intestine synthesize both peptide YY (PYY) and proglucagon-derived peptides (PGDPs), whose release has been reported to be either parallel or selective. Here we compare the release mechanisms of PYY, glucagon-like peptide-1 (GLP-1), and oxyntomodulin-like immunoreactivity (OLI) in vivo. Anaesthetized rats were intraduodenally (ID) given either a mixed semi-liquid meal or oleic acid, or they received oleic acid or short chain fatty acids (SCFA) intracolonically (IC).

Modulation of external pancreatic secretion by endogenous norepinephrine: study with a norepinephrine uptake blocker in the rat.

The effect of endogenous catecholamines on pancreatic secretion was analyzed with nisoxetine, a specific norepinephrine uptake blocker, and specific adrenoceptor antagonists in anesthetized acute fistula rats. Nisoxetine was administered alone or with alpha-1 (prazosin), alpha-2 (idazoxan or yohimbine), or beta (propranolol) adrenoceptor antagonists. Pancreatic secretion was measured in basal conditions or after stimulation by 2-deoxy-D-glucose (2DG), electrical vagal stimulation, or acetylcholine.

Neural modulation of cephalexin intestinal absorption through the di- and tripeptide brush border transporter of rat jejunum in vivo.

Intestinal absorption of beta-lactamine antibiotics (e.g., cefixime and cephalexin) has been shown to proceed through the dipeptide carrier system.

Inhibitory effects of peptide YY on basal and VIP-stimulated short-circuit current in the rat jejunum: influence of technical conditions on observed results.

The interaction of PYY and VIP was studied in stripped and intact rat jejunum preparations mounted in Ussing chambers. PYY decreased basal Isc in intact as well as in stripped jejunum. Stripping was necessary to evidence a stimulation of basal Isc by VIP.

Neural modulation of the antisecretory effect of peptide YY in the rat jejunum.

The endocrine and neural peptide, peptide YY, inhibits intestinal secretion of water and electrolytes in several animal species and in man. Peptide YY receptors have been evidenced on isolated rat jejunal crypt cells, but neural receptors are also likely to participate in the antisecretory effect of peptide YY in vivo. The aim of the present study was to investigate the mechanisms of the peptide YY effect on vasoactive intestinal peptide (VIP)-stimulated jejunal net water flux in the rat.

Mechanisms of peptide YY release induced by an intraduodenal meal in rats: neural regulation by proximal gut.

Peptide YY (PYY) release in anaesthetized rats was studied during the 2 h following the intraduodenal administration of a semi-liquid meal of 21 kJ. Surgical and pharmacological manipulations were performed in order to analyse the mechanisms of PYY release. Postprandial PYY release was suppressed or strongly decreased by caecocolonectomy, truncal vagotomy, tetrodotoxin, hexamethonium, sensory denervation by perivagal capsaicin, and by the NO-synthase inhibitor L-N-arginine methyl ester, while atropine, adrenergic blockers, antagonists of type-A or type-B cholecystokinin (CCK) receptors or bombesin receptors had no effect.

Several receptors mediate the antisecretory effect of peptide YY, neuropeptide Y, and pancreatic polypeptide on VIP-induced fluid secretion in the rat jejunum in vivo.

Several Y receptor subtypes have been cloned and/or pharmacologically characterized that mediate the effects of the regulatory peptides peptide YY (PYY), neuropeptide Y (NPY), and pancreatic polypeptide (PP). These peptides possess antisecretory properties on the intestine. This effect can be blocked in vivo by neural antagonists, suggesting the intervention of neural receptors, although epithelial PYY-preferring receptors have been evidenced on jejunal crypt cells.

Release of nonesterified fatty acids during cerulein-induced pancreatitis in rats.

During acute pancreatitis, data obtained in vitro suggest that pancreatic lipase, acting on circulating or tissular triglycerides, might generate nonesterified fatty acids (NEFA) that could promote pancreatic and fat tissue necrosis. This work determined whether NEFA were actually produced in vivo in pancreatic tissue and in blood during cerulein-induced pancreatitis in rats. Intraperitoneal injections of cerulein induced pancreatitis.

[Antisecretory effects of YY peptide and neuropeptide Y at three levels of the small intestine in rats].

Objectives And Methods: The purpose of this study was to compare the effects of peptide YY (PYY) and neuropeptide Y (NPY) on VIP- and PGE2-stimulated intestinal net water flux at three different levels of the small intestine (duodenum, jejunum, ileum), by a technique of in situ closed loops in anaesthetised rats.

Results: VIP-stimulated net water flux was efficiently inhibited by both peptides at all three intestinal levels studied; PYY (ID50 about 30 pmol/kg.h) was 3 to 18 fold more potent than NPY.

Peptide YY release after intraduodenal, intraileal, and intracolonic administration of nutrients in rats.

Peptide YY (PYY) release was studied by measuring radioimmunoassayable PYY in the arterial plasma of anaesthetized rats receiving into the duodenum, ileum or colon either a complete semi-liquid meal (3ml, 21kJ) or elemental nutrients as isocaloric or isoosmolar solutions. PYY release induced by the intraduodenal meal peaked at 60min and lasted more than 120min. The integrated response of PYY over 120min was larger when the meal was administered into the duodenum than into the ileum.

[Simultaneous study of duodenal and biliopancreatic bicarbonates in rats].

Objectives: The aim of the present study was to assess the relative contribution of duodenal and biliopancreatic bicarbonate secretion to acid neutralization in the duodenum, in basal conditions, during stimulation by PGE2 and during acid infusion in the duodenum.

Methods: Forty rats were anaesthetized and the duodenum was infused with 0.9% saline.

Nonesterified fatty acids in acute cerulein-induced pancreatitis in the rat. Are they really deleterious in vivo?

During acute pancreatitis, experimental data obtained in vitro suggested that pancreatic lipase generates nonesterified fatty acids (NEFA), noxious for acinar cells, by hydrolysis of pancreatic or circulating triglycerides. The purpose of this work was to determine whether experimentally induced high plasma NEFA levels do indeed aggravate in vivo cerulein-induced pancreatitis. Anesthetized Sprague-Dawley rats received cerulein and were simultaneously infused intravenously with either saline or a triglyceride + heparin mixture (TGH) in order to increase the amount of circulating NEFA.

Differential effects of peptide YY, neuropeptide Y, and sigma ligands on neurally stimulated external pancreatic secretion in the rat.

The endocrine peptide YY (PYY) inhibits pancreatic secretion in animals and in man through indirect pathways. Neuropeptide Y (NPY), whose chemical structure is very close, displays similar effects. Recently, sigma ligands were shown to produce in vivo several neural pharmacologic effects that seemed indistinguishable from those of NPY.

Modulation of pancreatic secretion by capsaicin-sensitive sensory neurons in the rat.

The purpose of this work was to study whether stimulation or destruction of sensory afferents can modulate pancreatic secretion. The neurotoxin capsaicin is specific for a subpopulation of small diameter primary afferent neurons. Small doses of capsaicin were administered to anesthetized rats as intraduodenal or intragastric bolus injections to stimulate digestive sensory fibers, and pancreatic secretory response was measured.

[Free fatty acids and acute pancreatitis. An in vivo experimental study].

Experimental in vitro studies support a theory which attributes a key role to pancreatic lipase in the physiopathology of acute pancreatitis. Pancreatic lipase would hydrolyse triglycerides either in circulation or in tissues, releasing Free Fatty Acids (F.F.

Mechanism of neurotensin stimulation of external pancreatic secretion in the rat.

The gut and brain peptide neurotensin has been claimed to directly or indirectly stimulate external pancreatic secretion. The purpose of this study was to analyze the mechanism of the neurotensin effect on external pancreatic secretion in the rat. The pancreatic dose-response curve to 40-min venous infusions of neurotensin 1-13 (0.

[Effect of nalbuphine on external pancreatic secretion in rats].

Pancreatic secretion is controlled by neural and endocrine mechanisms. The administration of 2-desoxyglucose (2DG) to rats stimulates pancreatic secretion through a mainly vagal pathway, and provides an useful pharmacological model to study the agents (especially opiates and adrenergic drugs) which can modulate this neural pathway. In the present study, basal and 2DG-stimulated pancreatic secretion were measured in anesthetized rats.

[Sensory fibers sensitive to capsaicin can modulate secretion of the duodenal mucus. A morphometric study in rats].

Many in vitro and in vivo models have been used to study the modulation of intestinal mucosecretion. In such studies, quantification of mucus secretion is usually difficult, due to several technical problems. Whether sensory mechanisms participate in the modulation of intestinal mucosecretion remains unknown.