Increased food intake and CCK receptor antagonists: beyond abdominal vagal afferents

2004 ◽  
Vol 286 (6) ◽  
pp. R991-R993 ◽  
Author(s):  
Robert C. Ritter
Keyword(s):  
Food Intake ◽  
Vagal Afferents ◽  
Receptor Antagonists ◽  
Cck Receptor Antagonists

Cholecystokinin suppresses food intake by a nonendocrine mechanism in rats

1994 ◽  
Vol 267 (4) ◽  
pp. R901-R908 ◽  
Author(s):  
R. D. Reidelberger ◽  
G. Varga ◽  
R. M. Liehr ◽  
D. A. Castellanos ◽  
G. L. Rosenquist ◽  
...  
Keyword(s):  
Food Intake ◽  
Pancreatic Enzyme ◽  
Free Access ◽  
Amylase Secretion ◽  
Receptor Antagonists ◽  
Feeding Experiments ◽  
Pancreatic Enzyme Secretion ◽  
Endocrine Mechanism ◽  
Access To Food ◽  
Cck Receptor Antagonists

A cholecystokinin monoclonal antibody (CCK MAb) was used to immunoneutralize CCK to test the hypothesis that CCK produces satiety by an endocrine mechanism. We first characterized the effects of CCK MAb on pancreatic secretion. Conscious rats with jugular vein and bile-pancreatic duct cannulas received CCK MAb or control antibody intravenously 30 min before a 2-h maximal dose of CCK-8 (200 pmol.kg-1.h-1 i.v.) or access to food. CCK MAb caused dose-related inhibition of amylase secretion. CCK MAb (2 mg/kg) completely blocked the response to CCK-8 and inhibited the response to food by 89%. In feeding experiments, rats with free access to food received CCK MAb or control antibodies (2 mg/kg iv) 2 h after lights off. CCK MAb had no effect on 1.5- or 3.5-h food intake. Another group of rats received CCK MAb (4 mg/kg i.v.) or a combined injection of type A and type B CCK receptor antagonists devazepide and L-365,260 (1 mg/kg each i.v.). CCK MAb had no effect on feeding, whereas the receptor antagonists stimulated 1-, 2-, 3-, and 4-h intake by 62, 45, 43, and 29%. These results suggest that endogenous CCK stimulates pancreatic enzyme secretion at least partially by an endocrine mechanism and produces satiety by a nonendocrine mechanism.

The Effect of Centrally Administered CCK-Receptor Antagonists on Food Intake in Rats

1997 ◽  
Vol 61 (6) ◽  
pp. 823-827 ◽  
Author(s):  
Eric S Corp ◽  
Michael Curcio ◽  
James Gibbs ◽  
Gerard P Smith
Keyword(s):  
Food Intake ◽  
Receptor Antagonists ◽  
Cck Receptor Antagonists

CCK is involved in both peripheral and central mechanisms controlling food intake in chickens

1997 ◽  
Vol 272 (1) ◽  
pp. R334-R340 ◽  
Author(s):  
A. Rodriguez-Sinovas ◽  
E. Fernandez ◽  
X. Manteca ◽  
A. G. Fernandez ◽  
E. Gonalons
Keyword(s):  
Food Intake ◽  
Receptor Antagonist ◽  
Receptor Type ◽  
Receptor Antagonists ◽  
Cck Receptors ◽  
High Affinity ◽  
Increase Food Intake ◽  
Cck Receptor Antagonist ◽  
Cck Receptor Antagonists ◽  
Voluntary Food Intake

The aim of this work was to study the involvement of cholecystokinin (CCK) in the control of food intake in chickens. The following aspects were studied: 1) the effects of intravenous and intracerebroventricular sulfated octapeptide of CCK (CCK-8s) on voluntary food intake; 2) the effects of two CCK-receptor antagonists. L-365,260 and L-364,718, on food intake; and 3) the ability of such drugs to block the effects of CCK-8s on food intake in the chicken. Intravenous and intracerebroventricular CCK-8s caused a decrease in food intake. Intraperitoneal L-365,260, a CCK-receptor antagonist with low affinity for the two CCK receptors described in the chicken, increases food intake. Intracerebroventricular L-364,718, a drug that has high affinity for the chicken central CCK-receptor type, increased food intake. The effect of intravenous CCK-8s on food intake was not blocked by L-364,718 or L-365,260, whereas that of intracerebroventricular CCK-8s was blocked by intracerebroventricular L-364,718. It is concluded that central endogenous CCK plays a role in the control of food intake, which is dependent on central CCK-receptor type; nevertheless, peripheral CCK also decreases food intake acting on the peripheral CCK-receptor type. The fact that intracerebroventricular L-364,718 is able to increase food intake is related to its high affinity for the central CCK-receptor type of this species. Finally, three different speculations that might explain the fact that intraperitoneal L-365,260 increases food intake are discussed.

scholarly journals Reduction of food intake by cholecystokinin requires activation of hindbrain NMDA-type glutamate receptors

2011 ◽  
Vol 301 (2) ◽  
pp. R448-R455 ◽  
Author(s):  
Jason Wright ◽  
Carlos Campos ◽  
Thiebaut Herzog ◽  
Mihai Covasa ◽  
Krzysztof Czaja ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Food Intake ◽  
Nmda Receptors ◽  
Receptor Antagonist ◽  
Fourth Ventricle ◽  
Nmda Receptor Antagonist ◽  
Behavioral Pattern ◽  
Vagal Afferents ◽  
Nmda Receptor Antagonists ◽  
The Brain

Intraperitoneal injection of CCK reduces food intake and triggers a behavioral pattern similar to natural satiation. Reduction of food intake by CCK is mediated by vagal afferents that innervate the stomach and small intestine. These afferents synapse in the hindbrain nucleus of the solitary tract (NTS) where gastrointestinal satiation signals are processed. Previously, we demonstrated that intraperitoneal (IP) administration of either competitive or noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonists attenuates reduction of food intake by CCK. However, because vagal afferents themselves express NMDA receptors at both central and peripheral endings, our results did not speak to the question of whether NMDA receptors in the brain play an essential role in reduction of feeding by CCK. We hypothesized that activation of NMDA receptors in the NTS is necessary for reduction of food intake by CCK. To test this hypothesis, we measured food intake following IP CCK, subsequent to NMDA receptor antagonist injections into the fourth ventricle, directly into the NTS or subcutaneously. We found that either fourth-ventricle or NTS injection of the noncompetitive NMDA receptor antagonist MK-801 was sufficient to inhibit CCK-induced reduction of feeding, while the same antagonist doses injected subcutaneously did not. Similarly fourth ventricle injection of d-3-(2-carboxypiperazin-4-yl)-1-propenyl-1-phosphoric acid (d-CPPene), a competitive NMDA receptor antagonist, also blocked reduction of food intake following IP CCK. Finally, d-CPPene injected into the fourth ventricle attenuated CCK-induced expression of nuclear c-Fos immunoreactivity in the dorsal vagal complex. We conclude that activation of NMDA receptors in the hindbrain is necessary for the reduction of food intake by CCK. Hindbrain NMDA receptors could comprise a critical avenue for control and modulation of satiation signals to influence food intake and energy balance.

scholarly journals The common hepatic branch of the vagus is not required to mediate the glycemic and food intake suppressive effects of glucagon-like-peptide-1

2011 ◽  
Vol 301 (5) ◽  
pp. R1479-R1485 ◽  
Author(s):  
Matthew R. Hayes ◽  
Scott E. Kanoski ◽  
Bart C. De Jonghe ◽  
Theresa M. Leichner ◽  
Amber L. Alhadeff ◽  
...  
Keyword(s):  
Food Intake ◽  
Vagal Afferents ◽  
Oral Glucose ◽  
Afferent Fibers ◽  
The Common ◽  
Vagal Afferent ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
And Control ◽  
Hepatic Branch

The incretin and food intake suppressive effects of intraperitoneally administered glucagon-like peptide-1 (GLP-1) involve activation of GLP-1 receptors (GLP-1R) expressed on vagal afferent fiber terminals. Central nervous system processing of GLP-1R-driven vagal afferents results in satiation signaling and enhanced insulin secretion from pancreatic-projecting vagal efferents. As the vast majority of endogenous GLP-1 is released from intestinal l-cells following ingestion, it stands to reason that paracrine GLP-1 signaling, activating adjacent GLP-1R expressed on vagal afferent fibers of gastrointestinal origin, contributes to glycemic and food intake control. However, systemic GLP-1R-mediated control of glycemia is currently attributed to endocrine action involving GLP-1R expressed in the hepatoportal bed on terminals of the common hepatic branch of the vagus (CHB). Here, we examine the hypothesis that activation of GLP-1R expressed on the CHB is not required for GLP-1's glycemic and intake suppressive effects, but rather paracrine signaling on non-CHB vagal afferents is required to mediate GLP-1's effects. Selective CHB ablation (CHBX), complete subdiaphragmatic vagal deafferentation (SDA), and surgical control rats received an oral glucose tolerance test (2.0 g glucose/kg) 10 min after an intraperitoneal injection of the GLP-1R antagonist, exendin-(9–39) (Ex-9; 0.5 mg/kg) or vehicle. CHBX and control rats showed comparable increases in blood glucose following blockade of GLP-1R by Ex-9, whereas SDA rats failed to show a GLP-1R-mediated incretin response. Furthermore, GLP-1(7–36) (0.5 mg/kg ip) produced a comparable suppression of 1-h 25% glucose intake in both CHBX and control rats, whereas intake suppression in SDA rats was blunted. These findings support the hypothesis that systemic GLP-1R mediation of glycemic control and food intake suppression involves paracrine-like signaling on GLP-1R expressed on vagal afferent fibers of gastrointestinal origin but does not require the CHB.

New proglumide-analogue CCK receptor antagonists: very potent and selective for peripheral tissues

1986 ◽  
Vol 250 (6) ◽  
pp. G856-G860 ◽  
Author(s):  
C. Niederau ◽  
M. Niederau ◽  
J. A. Williams ◽  
J. H. Grendell
Keyword(s):  
Agonist Activity ◽  
Receptor Antagonists ◽  
Maximal Inhibition ◽  
Amylase Release ◽  
Peripheral Tissues ◽  
Pancreatic Acini ◽  
Cholecystokinin Receptor ◽  
Low Concentrations ◽  
Competitive Kinetics ◽  
Cck Receptor Antagonists

The present study evaluates the ability of two recently synthesized analogues of proglumide, both 4-benzamido-N,N-di-alkyl-glutaramic acid derivatives, to act as cholecystokinin receptor antagonists. Both new antagonists inhibited cholecystokinin-stimulated amylase release and, similarly, binding of 125I-cholecystokinin to isolated rat pancreatic acini. These effects displayed competitive kinetics; both antagonists showed no agonist activity and were specific in that only those secretagogues were inhibited that interact with the cholecystokinin receptor. Both antagonists also inhibited binding of 125I-cholecystokinin to mouse pancreatic membrane particles similarly to results with rat pancreatic acini. With the more potent of the two new antagonists, half-maximal inhibition of action and binding of cholecystokinin was observed with low concentrations of approximately 10(-7) M; compared with proglumide, the new antagonists were as much as 4,000 times more potent. Unlike proglumide, which inhibits binding of cholecystokinin to pancreas and brain tissue similarly, both antagonists inhibited binding of cholecystokinin to the pancreas at much lower concentrations compared with brain. The more potent of the inhibitors was 300 times more potent in inhibiting binding of cholecystokinin to pancreatic tissues compared with brain.

Peripheral oxytocin activates vagal afferent neurons to suppress feeding in normal and leptin-resistant mice: a route for ameliorating hyperphagia and obesity

2015 ◽  
Vol 308 (5) ◽  
pp. R360-R369 ◽  
Author(s):  
Yusaku Iwasaki ◽  
Yuko Maejima ◽  
Shigetomo Suyama ◽  
Masashi Yoshida ◽  
Takeshi Arai ◽  
...  
Keyword(s):  
Food Intake ◽  
Nucleus Tractus Solitarius ◽  
Body Weight Gain ◽  
Vagal Afferents ◽  
Afferent Neuron ◽  
Afferent Neurons ◽  
Vagal Afferent ◽  
Fos Expression ◽  
Novel Target ◽  
Anorexigenic Effect

Oxytocin (Oxt), a neuropeptide produced in the hypothalamus, is implicated in regulation of feeding. Recent studies have shown that peripheral administration of Oxt suppresses feeding and, when infused subchronically, ameliorates hyperphagic obesity. However, the route through which peripheral Oxt informs the brain is obscure. This study aimed to explore whether vagal afferents mediate the sensing and anorexigenic effect of peripherally injected Oxt in mice. Intraperitoneal Oxt injection suppressed food intake and increased c-Fos expression in nucleus tractus solitarius to which vagal afferents project. The Oxt-induced feeding suppression and c-Fos expression in nucleus tractus solitarius were blunted in mice whose vagal afferent nerves were blocked by subdiaphragmatic vagotomy or capsaicin treatment. Oxt induced membrane depolarization and increases in cytosolic Ca2+ concentration ([Ca2+]i) in single vagal afferent neurons. The Oxt-induced [Ca2+]i increases were markedly suppressed by Oxt receptor antagonist. These Oxt-responsive neurons also responded to cholecystokinin-8 and contained cocaine- and amphetamine-regulated transcript. In obese diabetic db/db mice, leptin failed to increase, but Oxt increased [Ca2+]i in vagal afferent neurons, and single or subchronic infusion of Oxt decreased food intake and body weight gain. These results demonstrate that peripheral Oxt injection suppresses food intake by activating vagal afferent neurons and thereby ameliorates obesity in leptin-resistant db/db mice. The peripheral Oxt-regulated vagal afferent neuron provides a novel target for treating hyperphagia and obesity.

Leptin and CCK modulate complementary background conductances to depolarize cultured nodose neurons

2006 ◽  
Vol 290 (2) ◽  
pp. C427-C432 ◽  
Author(s):  
J. H. Peters ◽  
R. C. Ritter ◽  
S. M. Simasko
Keyword(s):  
Food Intake ◽  
Outward Current ◽  
Vagal Afferents ◽  
Afferent Neurons ◽  
Inward Current ◽  
Adult Rat ◽  
Nodose Ganglia ◽  
Sodium Dependent ◽  
Ionic Mechanisms ◽  
Vagal Afferent

We have previously reported that intraceliac infusion of leptin induces a reduction of meal size that depends on intact vagal afferents. This effect of leptin is enhanced in the presence of cholecystokinin (CCK). The mechanisms by which leptin and CCK activate vagal afferent neurons are not known. In the present study, we have begun to address this question by using patch-clamp electrophysiological techniques to examine the mechanisms by which leptin and CCK activate cultured vagal afferents from adult rat nodose ganglia. We found that leptin depolarized 41 (60%) of 68 neurons. The magnitude of membrane depolarization was dependent on leptin concentration and occurred in both capsaicin-sensitive and capsaicin-insensitive neurons. We also found that a majority (16 of 22; 73%) of nodose neurons activated by leptin were also sensitive to CCK. CCK-induced depolarization was primarily associated with the increase of an inward current (11 of 12), whereas leptin induced multiple changes in background conductances through a decrease in an outward current (7 of 13), an increase in an inward current (3 of 13), or both (3 of 13). However, further isolation of background currents by recording in solutions that contained only sodium or only potassium revealed that both leptin and CCK were capable of increasing a sodium-dependent conductance or inhibiting a potassium-dependent conductance. Our results support the hypothesis that vagal afferents are a point of convergence and integration of leptin and CCK signaling for control of food intake and suggest multiple ionic mechanisms by which leptin and CCK activate vagal afferent neurons.

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