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.

Cholecystokinin-8s excites identified rat pancreatic-projecting vagal motoneurons

2007 ◽  
Vol 293 (2) ◽  
pp. G484-G492 ◽  
Author(s):  
Shuxia Wan ◽  
F. Holly Coleman ◽  
R. Alberto Travagli
Keyword(s):  
Brain Stem ◽  
Pancreatic Polypeptide ◽  
Potassium Conductance ◽  
Input Resistance ◽  
Exocrine Secretion ◽  
Motor Nucleus ◽  
Pancreatic Exocrine Secretion ◽  
Calcium Dependent ◽  
Synaptic Circuits ◽  
Pancreatic Exocrine

It is known that cholecystokinin (CCK) acts in a paracrine fashion to increase pancreatic exocrine secretion via vagal circuits. Recent evidence, however, suggests that CCK-8s actions are not restricted to afferent vagal fibers, but also affect brain stem structures directly. Within the brain stem, preganglionic neurons of the dorsal motor nucleus of the vagus (DMV) send efferent fibers to subdiaphragmatic viscera, including the pancreas. Our aims were to investigate whether DMV neurons responded to exogenously applied CCK-8s and, if so, the mechanism of action. Using whole cell patch-clamp recordings we show that perfusion with CCK-8s induced a concentration-dependent excitation in ∼60% of identified pancreas-projecting DMV neurons. The depolarization was significantly reduced by tetrodotoxin, suggesting both direct (on the DMV membrane) and indirect (on local synaptic circuits) effects. Indeed, CCK-8s increased the frequency of miniature excitatory currents onto DMV neurons. The CCK-A antagonist, lorglumide, prevented the CCK-8s-mediated excitation whereas the CCK-B preferring agonist, CCK-nonsulfated, had no effect, suggesting the involvement of CCK-A receptors only. In voltage clamp, the CCK-8s-induced inward current reversed at −106 ± 3 mV and the input resistance increased by 150 ± 15%, suggesting an effect mediated by the closure of a potassium conductance. Indeed, CCK-8s reduced both the amplitude and the time constant of decay of a calcium-dependent potassium conductance. When tested with pancreatic polypeptide (which reduces pancreatic exocrine secretion), cells that responded to CCK-8s with an excitation were, instead, inhibited by pancreatic polypeptide. These data indicate that CCK-8s may control pancreas-exocrine secretion also via an effect on pancreas-projecting DMV neurons.

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.

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.

scholarly journals Proteinase-activated receptor-2 (PAR-2): regulation of salivary and pancreatic exocrine secretion in vivo in rats and mice

2000 ◽  
Vol 129 (8) ◽  
pp. 1808-1814 ◽  
Author(s):  
Atsufumi Kawabata ◽  
Hiroyuki Nishikawa ◽  
Ryotaro Kuroda ◽  
Kenzo Kawai ◽  
Morley D Hollenberg
Keyword(s):  
Exocrine Secretion ◽  
Pancreatic Exocrine Secretion ◽  
Pancreatic Exocrine ◽  
Rats And Mice

C-type natriuretic peptide stimulates pancreatic exocrine secretion in the rat: Role of vagal afferent and efferent pathways

2007 ◽  
Vol 577 (1-3) ◽  
pp. 192-202 ◽  
Author(s):  
María E. Sabbatini ◽  
Myrian R. Rodríguez ◽  
Paula Dabas ◽  
Marcelo S. Vatta ◽  
Liliana G. Bianciotti
Keyword(s):  
Natriuretic Peptide ◽  
Exocrine Secretion ◽  
Pancreatic Exocrine Secretion ◽  
Efferent Pathways ◽  
Pancreatic Exocrine ◽  
Vagal Afferent

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)

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