Microinjection of TRH analogue into the dorsal vagal complex stimulates pancreatic secretion in rats

1995 ◽  
Vol 269 (3) ◽  
pp. G328-G334 ◽  
Author(s):  
T. Okumura ◽  
I. L. Taylor ◽  
T. N. Pappas
Keyword(s):  
Vagus Nerve ◽  
Pancreatic Secretion ◽  
Exocrine Secretion ◽  
Dependent Manner ◽  
Dorsal Vagal Complex ◽  
Pancreatic Exocrine Secretion ◽  
Pancreatic Fluid ◽  
Neurophysiological Studies ◽  
Pancreatic Exocrine ◽  
The Brain

Thyrotropin-releasing hormone (TRH) stimulates pancreatic exocrine secretion through the vagus nerve when injected into rat cerebrospinal fluid. However, little is known about the exact site of action of TRH in the brain to stimulate pancreatic secretion. Recent neuroimmunochemical and neurophysiological studies suggest that TRH could be a neurotransmitter in the dorsal vagal complex, which sends fibers to the pancreas through the vagus nerve. We therefore hypothesized that TRH may act centrally in the dorsal vagal complex to stimulate pancreatic exocrine secretion. To address this question, a TRH analogue, [1-methyl-(S)-4,5-dihydroorotyl]-L-histidyl-L-prolinamide- NH2, was microinjected into the dorsal vagal complex, and basal pancreatic fluid flow and protein secretion were measured in urethan-anesthetized rats. Microinjection of TRH analogue (0.2-2 ng/site) into the dorsal vagal complex significantly stimulated pancreatic flow and protein output in a dose-dependent manner. As a control, microinjection of the TRH analogue into the brain stem outside the vagal complex failed to stimulate pancreatic secretion. Either bilateral subdiaphragmatic vagotomy or atropine abolished the ability of the TRH analogue to stimulate pancreatic secretion. Our data suggest that TRH acts in the dorsal vagal complex to stimulate pancreatic secretion through vagus-dependent and cholinergic pathways. The dorsal vagal complex may play an important role as a central site for control of the exocrine pancreas.

scholarly journals MEK inhibits secretin release and pancreatic secretion: roles of secretin-releasing peptide and somatostatin

2001 ◽  
Vol 280 (5) ◽  
pp. G890-G896 ◽  
Author(s):  
James P. Li ◽  
Kae Yol Lee ◽  
Ta-Min Chang ◽  
William Y. Chey
Keyword(s):  
Pancreatic Secretion ◽  
Inhibitory Effect ◽  
Exocrine Secretion ◽  
Rabbit Serum ◽  
Normal Rabbit Serum ◽  
Pancreatic Exocrine Secretion ◽  
Pancreatic Fluid ◽  
Pancreatic Exocrine ◽  
Small Intestinal ◽  
Secretin Release

We investigated the mechanism of action of methionine enkephalin (MEK) on HCl-stimulated secretin release and pancreatic exocrine secretion. Anesthetized rats with pancreatobiliary cannulas and isolated upper small intestinal loops were perfused intraduodenally with 0.01 N HCl while bile and pancreatic juice were diverted. The effect of intravenous MEK on acid-stimulated secretin release and pancreatic exocrine secretion was then studied with or without coinfusion of naloxone, an anti-somatostatin (SS) serum, or normal rabbit serum. Duodenal acid perfusate, which contains secretin-releasing peptide (SRP) activity, was collected from donor rats with or without pretreatment with MEK, MEK + naloxone, or MEK + anti-SS serum, concentrated by ultrafiltration, and neutralized. The concentrated acid perfusate (CAP), which contains SRP bioactivity, was infused intraduodenally into recipient rats. MEK increased plasma SS concentration and inhibited secretin release and pancreatic fluid and bicarbonate secretion dose-dependently. The inhibition was partially reversed by naloxone and anti-SS serum but not by normal rabbit serum. In recipient rats, CAP increased plasma secretin level and pancreatic secretion. CAP SRP bioactivity decreased when it was collected from MEK-treated donor rats; this was partially reversed by coinfusion with naloxone or anti-SS serum. These results suggest that in the rat, MEK inhibition of acid-stimulated pancreatic secretion and secretin release involves suppression of SRP activity release. Thus the MEK inhibitory effect appears to be mediated in part by endogenous SS.

Neurohormonal mechanism of pancreatic exocrine secretion stimulated by sodium oleate and L-tryptophan in dogs

1992 ◽  
Vol 263 (1) ◽  
pp. G12-G16 ◽  
Author(s):  
Y. H. Jo ◽  
Y. L. Lee ◽  
K. Y. Lee ◽  
T. M. Chang ◽  
W. Y. Chey
Keyword(s):  
Pancreatic Juice ◽  
Sodium Oleate ◽  
Pancreatic Secretion ◽  
Exocrine Secretion ◽  
Dependent Manner ◽  
Pancreatic Exocrine Secretion ◽  
Pancreatic Exocrine ◽  
Protein Output ◽  
Dose Dependent ◽  
Cck Release

In the present investigation, we have studied the effect of atropine on the pancreatic secretion stimulated by intraduodenal administration of either sodium oleate or exogenous cholecystokinin (CCK). In four dogs prepared with gastric and Thomas duodenal cannulas, pancreatic juice was collected for measurement of volume, bicarbonate, and protein output, and peripheral venous blood samples were obtained for radioimmunoassay of both secretin and CCK. Volume, bicarbonate, and protein output of the pancreatic juice increased significantly in response to sodium oleate (1-4 mmol/h) in a dose-dependent manner. The increase in pancreatic secretion paralleled the increments in both plasma CCK and secretin. Atropine given intravenously suppressed completely both pancreatic secretion and release of CCK stimulated by sodium oleate, whereas the release of secretin was not affected. Pancreatic secretion was significantly increased in a dose-dependent manner by exogenous CCK octapeptide (CCK-8) at 16, 32, and 64 micrograms (14, 28, and 56 pmol).kg-1.h-1. Atropine inhibited protein output only partially, but it did not influence bicarbonate output. In five additional dogs, the effect of atropine on L-tryptophan-stimulated pancreatic secretion was studied. Interestingly, atropine failed to influence the CCK release and pancreatic secretion of volume and bicarbonate, except for protein secretion, which was significantly inhibited. It was shown previously that atropine inhibited significantly the pancreatic secretion of bicarbonate stimulated by secretin in physiological doses. Thus we conclude that the inhibition by atropine of the pancreatic exocrine secretion stimulated by sodium oleate is mediated by both suppression of CCK release and inhibition of action of secretin on the exocrine pancreas.(ABSTRACT TRUNCATED AT 250 WORDS)

Central somatostatin prevents vagal efferent nerve excitation produced by TRH but not by 2-deoxy-D-glucose

1997 ◽  
Vol 272 (2) ◽  
pp. G351-G356 ◽  
Author(s):  
M. Masuda ◽  
S. Kanai ◽  
K. Miyasaka
Keyword(s):  
Intravenous Injection ◽  
Pancreatic Secretion ◽  
Exocrine Secretion ◽  
Dependent Manner ◽  
Pancreatic Exocrine Secretion ◽  
Efferent Nerve ◽  
Trh Stimulation ◽  
Pancreatic Exocrine ◽  
Nerve Excitation ◽  
Vagal Efferent Nerve

Thyrotropin-releasing hormone (TRH) administered intracerebroventricularly and intravenous injection of 2-deoxy-D-glucose (2-DG) stimulate pancreatic exocrine secretion via vagal efferent nerve excitation. We examined whether centrally administered somatostatin would inhibit pancreatic exocrine secretion that was stimulated by vagal efferent nerve excitation in conscious rats. The animals were prepared with cannulas draining bile and pancreatic juice separately and with a duodenal cannula, a cerebroventricular cannula, and a right jugular vein cannula. Intracerebroventricular injection of somatostatin (0.4 or 4 nmol) significantly inhibited pancreatic secretion induced by TRH (50 or 500 pmol) in a dose-dependent manner. Intravenous injection of somatostatin had no effect on pancreatic secretion stimulated by TRH. On the other hand, somatostatin injected centrally did not affect pancreatic secretion induced by 2-DG (75 mg/kg) or basal secretion. These results suggest that TRH and 2-DG stimulate vagal efferent nerves via distinct mechanisms and that central somatostatin selectively inhibits excitation of the vagus induced by peptidergic (TRH) stimulation.

Vagally mediated, nonparacrine effects of cholecystokinin-8s on rat pancreatic exocrine secretion

2007 ◽  
Vol 293 (2) ◽  
pp. G493-G500 ◽  
Author(s):  
Eddy Viard ◽  
Zhongling Zheng ◽  
Shuxia Wan ◽  
R. Alberto Travagli
Keyword(s):  
Brain Stem ◽  
Protein Secretion ◽  
Exocrine Secretion ◽  
Vagal Afferents ◽  
Dependent Manner ◽  
Pancreatic Exocrine Secretion ◽  
Sprague Dawley ◽  
Pancreatic Exocrine ◽  
Vagal Afferent

Cholecystokinin (CCK) has been proposed to act in a vagally dependent manner to increase pancreatic exocrine secretion via actions exclusively at peripheral vagal afferent fibers. Recent evidence, however, suggests the CCK-8s may also affect brain stem structures directly. We used an in vivo preparation with the aims of 1) investigating whether the actions of intraduodenal casein perfusion to increase pancreatic protein secretion also involved direct actions of CCK at the level of the brain stem and, if so, 2) determining whether, in the absence of vagal afferent inputs, CCK-8s applied to the dorsal vagal complex (DVC) can also modulate pancreatic exocrine secretion (PES). Sprague-Dawley rats (250–400 g) were anesthetized and the common bile-pancreatic duct was cannulated to collect PES. Both vagal deafferentation and pretreatment with the CCK-A antagonist lorglumide on the floor of the fourth ventricle decreased the casein-induced increase in PES output. CCK-8s microinjection (450 pmol) in the DVC significantly increased PES; the increase was larger when CCK-8s was injected in the left side of the DVC. Protein secretion returned to baseline levels within 30 min. Microinjection of CCK-8s increased PES (although to a lower extent) also in rats that underwent complete vagal deafferentation. These data indicate that, as well as activating peripheral vagal afferents, CCK-8s increases pancreatic exocrine secretion via an action in the DVC. Our data suggest that the CCK-8s-induced increases in PES are due mainly to a paracrine effect of CCK; however, a relevant portion of the effects of CCK is due also to an effect of the peptide on brain stem vagal circuits.

Effect of [(CH2NH)4,5]secretin on pancreatic exocrine secretion in guinea pigs and rats

1993 ◽  
Vol 265 (5) ◽  
pp. G805-G810 ◽  
Author(s):  
C. D. Kim ◽  
P. Li ◽  
K. Y. Lee ◽  
D. H. Coy ◽  
W. Y. Chey
Keyword(s):  
Pancreatic Secretion ◽  
Guinea Pigs ◽  
Partial Agonist ◽  
Inhibitory Effect ◽  
Exocrine Secretion ◽  
Pancreatic Exocrine Secretion ◽  
Pancreatic Acini ◽  
Secretin Receptor ◽  
Pancreatic Exocrine

[psi 4,5]Secretin was shown to be a secretin receptor antagonist that inhibits secretin-stimulated increase in adenosine 3',5'-cyclic monophosphate in isolated pancreatic acini of the guinea pig. To determine whether it inhibits pancreatic exocrine secretion in vivo, we have studied the effect of [psi 4,5]secretin on the pancreatic secretion stimulated by secretin in anesthetized guinea pigs and rats. In basal state, [psi 4,5]secretin given intravenously for 2 or 3 h in varying doses of 1.6-32.7 nmol.kg-1.h-1 dose dependently increased pancreatic secretion of both fluid and bicarbonate during the 1st h, but it returned gradually to basal level within 2 or 3 h. On the other hand, [psi 4,5]secretin significantly inhibited the pancreatic secretion stimulated by either exogenous or endogenous secretin in a dose-related manner. The inhibitory effect of [psi 4,5]secretin in guinea pigs was greater than that in rats. However, it did not completely block the secretin-stimulated pancreatic secretion, whereas a rabbit antisecretin serum suppressed it completely. We conclude that 1) in the unstimulated state, [psi 4,5]secretin is a partial agonist of pancreatic exocrine secretion of both fluid and bicarbonate; and 2) when pancreatic secretion is stimulated by secretin, unlike an antisecretin serum, it is a partial inhibitor in intact guinea pigs and rats.

Effect of ACh and calmodulin inhibitor on O2 transfer from exocrine pancreatic microvessels of rats

1996 ◽  
Vol 271 (1) ◽  
pp. H1-H7 ◽  
Author(s):  
A. Seiyama ◽  
H. Kosaka ◽  
T. Shiga
Keyword(s):  
Pancreatic Secretion ◽  
Binding Protein ◽  
Control Level ◽  
Exocrine Secretion ◽  
The Other ◽  
Pancreatic Exocrine Secretion ◽  
O2 Extraction ◽  
Pancreatic Exocrine ◽  
O2 Transfer ◽  
Krebs Henseleit Buffer

Effects of acetylcholine (ACh) and calmodulin (CaM) inhibitor, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride (W-7), on the rate of O2 release (Ro2) from single exocrine pancreatic microvessels of anesthetized rats were investigated with dual-spot microspectroscopy. The surface of the pancreas was superfused with Krebs-Henseleit buffer containing various concentrations of ACh and/or W-7. Superfusion of ACh (> or = 20 microM) elevated Ro2 as well as pancreatic secretion approximately 2.5 times higher than that of control level, whereas superfusion of W-7 (> or = 100 microM) reduced approximately 50%. In both cases, O2 inflow in single microvessels, as quantified by oxyhemoglobin inflow into the microvessels, was maintained at control level. On the other hand, superfusion of both ACh and W-7 did not modify Ro2 and pancreatic secretion, despite significant reduction in O2 inflow. These results indicate that 1) the ACh-induced elevation of O2 release from single microvessels is accomplished by increased O2 extraction instead of increased O2 inflow in the microvessels, and 2) the activity of a W-7-sensitive Ca2+ binding protein, most likely CaM, is responsible for half of the microvascular O2 transfer and of the pancreatic exocrine secretion.

Inhibitory effect of central dopamine on basal pancreatic secretion in conscious rats

1998 ◽  
Vol 274 (1) ◽  
pp. G29-G34 ◽  
Author(s):  
Masao Masuda ◽  
Setsuko Kanai ◽  
Kyoko Miyasaka
Keyword(s):  
Pancreatic Secretion ◽  
Sch 23390 ◽  
Sympathetic Nerves ◽  
Inhibitory Effect ◽  
Exocrine Secretion ◽  
External Jugular Vein ◽  
Pancreatic Exocrine Secretion ◽  
Conscious Rats ◽  
Brain Ventricle ◽  
Pancreatic Exocrine

We examined the role and the peripheral mechanism of action of central dopamine on basal pancreatic exocrine secretion in conscious rats. Rats were fitted with bile and pancreatic catheters to collect bile and pancreatic juice separately and also with a left lateral brain ventricle and external jugular vein catheters. After 90-min basal collection, the D1- and D2-receptor antagonists (Sch-23390 and eticlopride, respectively) and dopamine were administered into the lateral brain ventricle. Sch-23390 (30, 100, and 300 nmol/rat), but not eticlopride (300 nmol/rat), stimulated pancreatic fluid and protein secretion. Dopamine (30, 100, and 300 nmol/rat) inhibited pancreatic secretion dose dependently. Pretreatment with Sch-23390 prevented the inhibitory effect of dopamine. Intravenously injected Sch-23390 or dopamine had no effect on pancreatic secretion. The inhibitory effect of dopamine was blocked by bretylium, an inhibitor of norepinephrine release, and phentolamine, an α-blocker, but not by vagotomy. The β-antagonist propranolol alone significantly inhibited basal pancreatic secretion, and dopamine did not modify the inhibitory effect of propranolol. The proton pump inhibitor omeprazole partially but not completely reduced the inhibition by dopamine. These results suggest that central dopamine inhibits pancreatic exocrine secretion via D1-like receptors and that the inhibitory effect is mediated via sympathetic nerves, especially α-adrenoceptors.

Effects of slaframine and 4-diphenylacetoxy-N-methylpiperidine methiodide (4DAMP) on pancreatic exocrine secretion in the bovine

1994 ◽  
Vol 72 (1) ◽  
pp. 39-44 ◽  
Author(s):  
J. A. Walker ◽  
C. R. Krehbiel ◽  
D. L. Harmon ◽  
G. St. Jean ◽  
W. J. Croom Jr. ◽  
...  
Keyword(s):  
Latin Square ◽  
Fluid Secretion ◽  
Positive Control ◽  
Exocrine Secretion ◽  
Muscarinic Agonist ◽  
Pancreatic Exocrine Secretion ◽  
Pancreatic Fluid ◽  
Treatment Interaction ◽  
Quadratic Response ◽  
Pancreatic Exocrine

Three Holstein steers (345 ± 22 kg) surgically fitted with a pancreatic cannula were used in two 3 × 3 Latin square design experiments to examine the effects of slaframine (SF), a muscarinic agonist, or 4-diphenylacetoxy-N-methylpiperidine methiodide (4DAMP), an M3 muscarinic glandular receptor antagonist, on pancreatic exocrine secretion. Pancreatic exocrine secretion was collected for 8 h postdosing at 30-min intervals beginning 1 h postfeeding. In experiment 1, steers were dosed with 0, 25, or 50 μg∙kg−1 body weight (BW) of SF. Secretion of pancreatic juice and the pH of the secreted juice increased linearly (p < 0.05) with SF; however, secretion rate showed a time by treatment interaction (p < 0.05), as treatments converged 7 h postdosing. Trypsin secretion tended (p < 0.10) to show a quadratic response to SF administration, with the 25 μg SF∙kg−1 BW dose having the lowest value. In experiment 2, steers received 50 μg∙kg−1 BW of SF (positive control), 113 μg∙kg−1 BW of 4DAMP (isomolar with SF), or both. SF caused a greater pancreatic fluid secretion (p < 0.10) than 4DAMP, with SF plus 4DAMP intermediate. A time by treatment interaction (p < 0.04) was found, since treatments converged 8 h postdosing. Trypsin secretion was higher (p < 0.05) for SF than the other treatments. Chymotrypsin, α-amylase, and protein secretion were not affected. SF and 4DAMP alter pancreatic fluid secretion in the steer but have minimal effects on enzyme secretions.Key words: slaframine, 4-diphenylacetoxy-N-methylpiperidine methiodide, bovine, pancreatic exocrine secretion.

Peptide YY inhibits meal-stimulated pancreatic and gastric secretion

1985 ◽  
Vol 248 (1) ◽  
pp. G118-G123 ◽  
Author(s):  
T. N. Pappas ◽  
H. T. Debas ◽  
Y. Goto ◽  
I. L. Taylor
Keyword(s):  
Oleic Acid ◽  
Pancreatic Secretion ◽  
Peptide Yy ◽  
Potent Inhibitor ◽  
Liver Extract ◽  
Exocrine Secretion ◽  
Pancreatic Fluid ◽  
Meat Meal ◽  
Pancreatic Fistulas ◽  
Pancreatic Exocrine

Peptide YY was recently isolated from porcine intestine and shown to exhibit marked structural homology with pancreatic polypeptide, a potent inhibitor of pancreatic exocrine secretion. We have examined the effects of infused peptide YY on gastric and pancreatic secretion in four mongrel dogs with gastric and pancreatic fistulas. A 15% liver extract meal was instilled intragastrically, and normal saline or one of three doses of peptide YY (200, 400, and 800 pmol X kg-1 X h-1) was infused into a peripheral vein. All three doses of peptide YY significantly inhibited meal-stimulated pancreatic fluid and bicarbonate secretion, with the lowest dose inhibiting secretion by 44.5 +/- 3.5 and 53.6 +/- 8.5%, respectively. Pancreatic protein secretion and gastric acid secretion were significantly inhibited by the two highest doses. The 200, 400, and 800 pmol X kg-1 X h-1 doses of peptide YY were associated with increments in peripheral blood of 201 +/- 24, 357 +/- 50, and 971 +/- 139 pM, respectively. These values compared with mean increments of 86.3 +/- 8.5 pM after a meat meal and 403 +/- 63 pM after intestinally perfused oleic acid. The present studies demonstrate that peptide YY inhibits gastric and pancreatic secretion and suggest that peptide YY may be the gastric and pancreatic inhibitor in ileocolonic mucosa that is released by perfusion of the intestine with oleic acid.

Mechanism of action of insulin on pancreatic exocrine secretion in perfused rat pancreas

1994 ◽  
Vol 267 (2) ◽  
pp. G207-G212 ◽  
Author(s):  
K. Y. Lee ◽  
Y. L. Lee ◽  
C. D. Kim ◽  
T. M. Chang ◽  
W. Y. Chey
Keyword(s):  
Pancreatic Secretion ◽  
Exocrine Pancreas ◽  
Exocrine Secretion ◽  
Rabbit Serum ◽  
Normal Rabbit Serum ◽  
Pancreatic Exocrine Secretion ◽  
Arterial Infusion ◽  
Perfused Rat Pancreas ◽  
Pancreatic Exocrine ◽  
Protein Output

In conscious rats, we have previously shown that immunoneutralization of circulating insulin with a rabbit anti-insulin serum abolished the pancreatic exocrine secretion stimulated by a meal or a combination of exogenous secretin and cholecystokinin octapeptide (CCK-8). To investigate the mechanism of endogenous insulin action on the exocrine pancreas, isolated rat pancreata were perfused with intra-arterial infusion of Krebs-Henseleit solution (37 degrees C) at 1.2 ml/min, whereas both pancreatic juice and portal venous effluent were collected separately in 15-min samples. Simultaneous intra-arterial infusion of secretin and CCK-8 in doses of 0.75 and 4.2 pmol/h; respectively, significantly increased volume, bicarbonate, and protein output in 7 rat pancreata (P < 0.01). When a rabbit anti-insulin serum was administered intra-arterially (0.1-ml bolus followed by 0.1 ml for 10 min), pancreatic secretion of volume, bicarbonate, and protein output was profoundly suppressed (n = 7, P < 0.01), whereas a normal rabbit serum failed to influence pancreatic secretion. The decrease in pancreatic secretion by the antiserum coincided with a significant increase in somatostatin in portal venous effluent from 1.4 +/- 0.2 to 4.1 +/- 0.8 pM (n = 6, P < 0.05). The combined administration of a rabbit antisomatostatin serum (0.4 ml) and the anti-insulin serum partially reversed the effect of the anti-insulin serum alone. Thus the pancreatic secretion was significantly greater than that achieved by the anti-insulin serum alone (P < 0.05). These observations strongly suggest that the action of insulin on exocrine pancreas is mediated by its local or paracrine action.(ABSTRACT TRUNCATED AT 250 WORDS)

Sign in / Sign up

Export Citation Format

Share Document