Relationships between gastric motility and gastric vagal afferent responses to CCK and GRP in rats differ

1997 ◽  
Vol 272 (6) ◽  
pp. R1726-R1733 ◽  
Author(s):  
G. J. Schwartz ◽  
T. H. Moran ◽  
W. O. White ◽  
E. E. Ladenheim
Keyword(s):  
Gastric Motility ◽  
Direct Action ◽  
Muscle Tension ◽  
Vagal Afferents ◽  
Gut Peptides ◽  
Cck Receptors ◽  
Gastric Pressure ◽  
Vagal Afferent ◽  
Motor Effects ◽  
The Relationship

The brain-gut peptides cholecystokinin (CCK) and the mammalian bombesin-like peptide gastrin-releasing peptide (GRP) suppress food intake. Vagotomy blocks CCK- but not bombesin (BN)-induced feeding suppression, demonstrating differential vagal contributions. We examined the relationship between the ability of CCK and the active fragment of GRP, GRP-(18-27), to stimulate gastric vagal afferent activity and their ability to elicit changes in gastric motility. We also examined ligated cervical vagal segments and revealed specific 125I-CCK vagal binding without evidence of radiolabeled BN binding sites. Both close arterial and intraperitoneal CCK and GRP-(18-27) produced dose-dependent increases in activity in gastric vagal mechanoreceptive afferents. CCK dose dependently decreased gastric pressure without altering antral wall tension, whereas GRP-(18-27) dose dependently increased both gastric pressure and peak antral wall muscle tension. These results suggest that GRP-(18-27) activates gastric vagal afferents secondary to its stimulation of gastric motor effects. CCK activates this same population of vagal afferents independent of changes in gastric tension, suggesting a direct action of CCK at functional vagal CCK receptors.

Duodenal acid-induced gastric relaxation is mediated by multiple pathways

1999 ◽  
Vol 276 (6) ◽  
pp. G1501-G1506 ◽  
Author(s):  
Yuan-Xu Lu ◽  
Chung Owyang
Keyword(s):  
Gastric Motility ◽  
No Reduction ◽  
Direct Action ◽  
Intragastric Pressure ◽  
Afferent Pathways ◽  
Serotonin Antagonist ◽  
Intraduodenal Infusion ◽  
Rate Dependent ◽  
Vagal Afferent

In this study, we used an in vivo anesthetized rat model to investigate the mechanisms responsible for duodenal acid-induced inhibition of gastric motility. Intraduodenal infusion of HCl produced a rate-dependent decrease in intragastric pressure. Infusion of HCl at 2 ml/h produced a physiological plasma secretin level and elicited a decrease in intragastric pressure of 3.0 ± 0.2 cmH20. Infusion of rabbit secretin antiserum reduced the acid-induced inhibition of gastric motility by 85 ± 5%, suggesting mediation mainly by endogenous secretin. Administration of the cholecystokinin (CCK)-A antagonist MK-329 caused only a modest 10 ± 3% reduction in gastric relaxation, whereas the serotonin antagonist ICS-205930 had no effect. In contrast, immunoneutralization with the secretin antibody caused only a 15% reduction in the relaxation evoked by a higher rate of HCl infusion (3 ml/h), whereas MK-329 and ICS-205930 caused a 20 ± 4% reduction and no reduction, respectively. Bilateral truncal vagotomy or perivagal application of capsaicin completely abolished gastric relaxation in response to low rates (1–2 ml/h) of 0.1 N HCl infusion but only partially affected gastric relaxation in response to a higher infusion rate (3 ml/h). These observations indicate that multiple pathways mediate the duodenal acid-induced inhibition of gastric motility. At low rates of HCl infusion, gastric relaxation is mediated primarily by endogenous secretin, which acts through vagal afferent pathways. At higher rates of HCl infusion, gastric relaxation is mediated by endogenous secretin, CCK, and possibly by the direct action of HCl on vagal afferent pathways or yet unidentified neuropathways.

Abstract 20340: Defect of Ca 2+ -activated Cl - Channel in Intestinal Nodose Neurons Contributes to Impaired Satiety Signal in High-Fat Diet Induced Obesity

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Runping Wang ◽  
Yongjun Lu ◽  
Michael Z Cicha ◽  
Kamal Rahmouni ◽  
Mark W Chapleau ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Vagal Afferents ◽  
High Fat ◽  
Altered Expression ◽  
Cck Receptors ◽  
Whole Cell Patch Clamp ◽  
Nodose Ganglia ◽  
Maximum Current ◽  
Vagal Afferent ◽  
High Level

High fat diet inhibits the cholecystokinin (CCK) induced satiety signal in vagal afferents, which may contribute to the associated increased food intake. We hypothesized that a defect of Ca 2+ -activated chloride channel (CaCC) in high fat (HFD) fed mice leads to the reduction of CCK responses in intestinal vagal afferent nodose neurons. By using the whole cell patch-clamp in cultured nodose ganglia neurons isolated from C57BL/6 mice, we found that CCK (10nM) induced large inward chloride (Cl - ) currents (36.0±11pA/pF) that were eliminated with the fast Ca 2+ chelator BAPTA (1.0±0.5pA/pF, n=7), and reduced significantly by the CaCC channel inhibitor niflumic acid (100 μM, 13.6±2.0pA/pF, p<0.05, n=8). The response to CCK in DiI-labeled proximal intestinal nodose neurons from obese mice fed a 60% HFD for 10 weeks was reduced significantly (6.1±2.9pA/pF, n=7, p<0.01) relative to control lean mice (24.8±4.9pA/pF, n=7). The underlying molecular mechanism of the reduced CCK response in mice fed a HFD did not involve altered expression of CCK receptors in nodose neurons. We found that the relative mRNA (qPCR) of CCK receptor B was not significantly changed (1.01±0.13 in control vs. 1.18±0.31 in HFD nodose ganglia, n=4, p>0.05) and the mRNA of CCK receptor A was even increased from 1.06±0.37 in control to 1.54±0.41 in HFD ganglia (n=4, p<0.05). In contrast, the CaCC channel mRNA (Ano I) was decreased to 0.61±0.09 relative to 1.01±0.20 (n=4, p<0.001), and Ano II mRNA was decreased to 0.31±0.07 relative to 1.02±0.22 (n=4, p<0.001) in nodose ganglia from HFD fed vs. control lean mice. Since the maximum current induced by a saturation level of ligand reflects the level of protein expressed on the cytoplasmic membrane, we tested the CaCC current induced by a high level of intracellular Ca 2+ (20μM). We found that the maximum current was smaller in DiI labeled intestinal nodose neurons from HFD fed mice (13.7±2.9 pA/pF vs. 26.9±3.6 pA/pF in control mice, n=10, p<0.05). Our results indicate that CCK-activated currents recorded from intestinal vagal afferent nodose neurons are reduced in mice fed a HFD, and are associated with reduced expression of a CCK-activated Ca 2+ -dependent Cl - channel. This mechanism may contribute significantly to HFD-induced suppression of the satiety reflex.

scholarly journals Gastric relaxation induced by hyperglycemia is mediated by vagal afferent pathways in the rat

2008 ◽  
Vol 294 (5) ◽  
pp. G1158-G1164 ◽  
Author(s):  
Shi-Yi Zhou ◽  
Yuan-Xu Lu ◽  
Chung Owyang
Keyword(s):  
Gastric Motility ◽  
Electrical Field Stimulation ◽  
Glucose Sensing ◽  
Vagal Afferents ◽  
Dependent Manner ◽  
Intragastric Pressure ◽  
Synthesis Inhibitor ◽  
Afferent Pathways ◽  
Nodose Ganglia ◽  
Vagal Afferent

Hyperglycemia has a profound effect on gastric motility. However, little is known about the site and mechanism that sense alteration in blood glucose level. The identification of glucose-sensing neurons in the nodose ganglia led us to hypothesize that hyperglycemia acts through vagal afferent pathways to inhibit gastric motility. With the use of a glucose-clamp rat model, we showed that glucose decreased intragastric pressure in a dose-dependent manner. In contrast to intravenous infusion of glucose, intracisternal injection of glucose at 250 and 500 mg/dl had little effect on intragastric pressure. Pretreatment with hexamethonium, as well as truncal vagotomy, abolished the gastric motor responses to hyperglycemia (250 mg/dl), and perivagal and gastroduodenal applications of capsaicin significantly reduced the gastric responses to hyperglycemia. In contrast, hyperglycemia had no effect on the gastric contraction induced by electrical field stimulation or carbachol (10−5 M). To rule out involvement of serotonergic pathways, we showed that neither granisetron (5-HT3 antagonist, 0.5 g/kg) nor pharmacological depletion of 5-HT using p-chlorophenylalanine (5-HT synthesis inhibitor) affected gastric relaxation induced by hyperglycemia. Lastly, NG-nitro-l-arginine methyl ester (l-NAME) and a VIP antagonist each partially reduced gastric relaxation induced by hyperglycemia and, in combination, completely abolished gastric responses. In conclusion, hyperglycemia inhibits gastric motility through a capsaicin-sensitive vagal afferent pathway originating from the gastroduodenal mucosa. Hyperglycemia stimulates vagal afferents, which, in turn, activate vagal efferent cholinergic pathways synapsing with intragastric nitric oxide- and VIP-containing neurons to mediate gastric relaxation.

scholarly journals Evidence of activation of vagal afferents by non-invasive vagus nerve stimulation: An electrophysiological study in healthy volunteers

Cephalalgia ◽  
2017 ◽  
Vol 37 (13) ◽  
pp. 1285-1293 ◽  
Author(s):  
Romain Nonis ◽  
Kevin D’Ostilio ◽  
Jean Schoenen ◽  
Delphine Magis
Keyword(s):  
Vagus Nerve ◽  
Healthy Volunteers ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Electrophysiological Study ◽  
Vagal Afferents ◽  
Response Analysis ◽  
Bipolar Electrode ◽  
Non Invasive ◽  
Vagal Afferent

Background Benefits of cervical non-invasive vagus nerve stimulation (nVNS) devices have been shown in episodic cluster headache and preliminarily suggested in migraine, but direct evidence of vagus nerve activation using such devices is lacking. Vagal somatosensory evoked potentials (vSEPs) associated with vagal afferent activation have been reported for invasive vagus nerve stimulation (iVNS) and non-invasive auricular vagal stimulation. Here, we aimed to show and characterise vSEPs for cervical nVNS. Methods vSEPs were recorded for 12 healthy volunteers who received nVNS over the cervical vagus nerve, bipolar electrode/DS7A stimulation over the inner tragus, and nVNS over the sternocleidomastoid (SCM) muscle. We measured peak-to-peak amplitudes (P1-N1), wave latencies, and N1 area under the curve. Results P1-N1 vSEPs were observed for cervical nVNS (11/12) and auricular stimulation (9/12), with latencies similar to those described previously, whereas SCM stimulation revealed only a muscle artefact with a much longer latency. A dose-response analysis showed that cervical nVNS elicited a clear vSEP response in more than 80% of the participants using an intensity of 15 V. Conclusion Cervical nVNS can activate vagal afferent fibres, as evidenced by the recording of far-field vSEPs similar to those seen with iVNS and non-invasive auricular 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.

Radical Political Unionism as a Strategy for Revitalization in Argentina

2017 ◽  
Vol 45 (6) ◽  
pp. 97-113
Author(s):  
Lucila D’Urso ◽  
Julieta Longo
Keyword(s):  
Decision Making ◽  
Political Culture ◽  
Direct Action ◽  
The State ◽  
Social Organizations ◽  
Toma De Decisiones ◽  
Automotive Parts ◽  
The Relationship

The grassroots union experiment undertaken at the Lear automotive parts factory in Argentina can be seen as a paradigmatic struggle for an understanding of the relationship between unionism and politics. The Lear case reveals that the distinctiveness of radical political unionism lies in the democratic elements of its decision making and its appeal to direct action, its construction of alliances with other social organizations, its linkage of economic demands with broader political objectives, its identification of the management, the state, and the union bureaucracy as adversaries, and its transmission of a leftist political culture. La experiencia sindical de la fábrica de autopartes Lear en Argentina puede ser analizada como un conflicto paradigmático para comprender la relación entre sindicalismo y política. El caso de Lear revela que el carácter distintivo del sindicalismo político radical se encuentra en los mecanismos democráticos de toma de decisiones y en la apelación a medidas de acción directa, la construcción de alianzas con otras organizaciones sociales, la vinculación de las demandas económicas con objetivos políticos más amplios, la identificación de la empresa, el Estado y la burocracia sindical como adversarios y la transmisión de una cultura política de izquierda.

CCK enhances response to gastric distension by acting on capsaicin-insensitive vagal afferents

2005 ◽  
Vol 289 (3) ◽  
pp. R695-R703 ◽  
Author(s):  
E. H. E. M. van de Wall ◽  
P. Duffy ◽  
R. C. Ritter
Keyword(s):  
Vagal Afferents ◽  
Gastric Distension ◽  
Solitary Tract ◽  
C Fibers ◽  
Balloon Distension ◽  
Electrophysiological Responses ◽  
Vagal Afferent ◽  
Fos Expression ◽  
Afferent Response ◽  
And Control

Capsaicin treatment destroys vagal afferent C fibers and markedly attenuates reduction of food intake and induction of hindbrain Fos expression by CCK. However, both anatomical and electrophysiological data indicate that some gastric vagal afferents are not destroyed by capsaicin. Because CCK enhances behavioral and electrophysiological responses to gastric distension in rats and people, we hypothesized that CCK might enhance the vagal afferent response to gastric distension via an action on capsaicin-insensitive vagal afferents. To test this hypothesis, we quantified expression of Fos-like immunoreactivity (Fos) in the dorsal vagal complex (DVC) of capsaicin-treated (Cap) and control rats (Veh), following gastric balloon distension alone and in combination with CCK injection. In Veh rats, intraperitoneal CCK significantly increased DVC Fos, especially in nucleus of the solitary tract (NTS), whereas in Cap rats, CCK did not significantly increase DVC Fos. In contrast to CCK, gastric distension did significantly increase Fos expression in the NTS of both Veh and Cap rats, although distension-induced Fos was attenuated in Cap rats. When CCK was administered during gastric distension, it significantly enhanced NTS Fos expression in response to distension in Cap rats. Furthermore, CCK's enhancement of distension-induced Fos in Cap rats was reversed by the selective CCK-A receptor antagonist lorglumide. We conclude that CCK directly activates capsaicin-sensitive C-type vagal afferents. However, in capsaicin-resistant A-type afferents, CCK's principal action may be facilitation of responses to gastric distension.

Responses of celiac and cervical vagal afferents to infusions of lipids in the jejunum or ileum of the rat

2000 ◽  
Vol 278 (1) ◽  
pp. R34-R43 ◽  
Author(s):  
Alan Randich ◽  
William J. Tyler ◽  
James E. Cox ◽  
Stephen T. Meller ◽  
Gary R. Kelm ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Linoleic Acid ◽  
Single Unit ◽  
Corn Oil ◽  
Body Weight Gain ◽  
Vagal Afferents ◽  
Afferent Activity ◽  
Inhibitory Effects ◽  
Vagal Afferent ◽  
Increased Activity

Multiunit celiac and single-unit cervical recordings of vagal afferents were performed before and during infusions of fatty acids, triglycerides, or saline into either the ileum or jejunum of the rat. In multiunit recordings, lipids increased activity of vagal afferents to a greater extent than saline. The greatest increases in vagal afferent activity resulted from infusions of linoleic acid, conjugated linoleic acid, or oleic acid. The triglycerides, corn oil or Intralipid, were less effective than the fatty acids in affecting vagal afferent activity. Ileal pretreatment with the hydrophobic surfactant Pluronic L-81 significantly attenuated the response of celiac vagal afferents to ileal infusion of linoleic acid. Single-unit recordings of cervical vagal afferents supported the multiunit data in showing lipid-induced increased vagal afferent activity in ∼50% of ileal units sampled and 100% of a limited number of jejunal units sampled. These data demonstrate that free fatty acids can activate ileal and jejunal vagal afferents in the rat, and this effect can be attenuated by pretreatment with a chylomicron inhibitor. These data are consistent with the view that lipid-induced activation of vagal afferents could be a potential substrate for the inhibitory effects of intestinal lipids on gastrointestinal function, food intake, and body weight gain.

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.

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