scholarly journals Cooperative Activation of Cultured Vagal Afferent Neurons by Leptin and Cholecystokinin

Endocrinology ◽  
2004 ◽  
Vol 145 (8) ◽  
pp. 3652-3657 ◽  
Author(s):  
J. H. Peters ◽  
A. B. Karpiel ◽  
R. C. Ritter ◽  
S. M. Simasko
Keyword(s):  
Primary Cultures ◽  
Cytosolic Calcium ◽  
Extracellular Calcium ◽  
Vagal Afferents ◽  
Afferent Neurons ◽  
Adult Rat ◽  
Nodose Ganglia ◽  
Vagal Afferent ◽  
Acute Changes ◽  
And Control

Abstract To test the hypothesis that leptin can directly activate vagal afferent neurons, we used fluorescence imaging to detect acute changes in cytosolic calcium after leptin application to primary cultures of vagal afferent neurons dissociated from adult rat nodose ganglia. We found that approximately 40% of vagal afferent neurons exposed to leptin (40 ng/ml) responded with rapid and reversible increases in cytosolic calcium. These responses were dependent upon extracellular calcium. As previously reported, about 35% of vagal afferents increase cytosolic calcium in response to the gut-peptide cholecystokinin (CCK). A majority (74%) of neurons that responded to CCK also exhibited increases in cytosolic calcium in response to leptin. In addition, synergistic increases in cytosolic calcium were observed when leptin and CCK were applied in combination. These results demonstrate that leptin acts directly on vagal afferent neurons to trigger acute influxes of extracellular calcium. Our results also suggest cooperation between leptin and CCK in the activation of some vagal afferent neurons. Acute activation of vagal afferents by leptin alone and in combination with CCK may contribute to modulation of visceral reflexes and control of food intake.

Cholecystokinin increases cytosolic calcium in a subpopulation of cultured vagal afferent neurons

2002 ◽  
Vol 283 (6) ◽  
pp. R1303-R1313 ◽  
Author(s):  
Steven M. Simasko ◽  
Jason Wiens ◽  
Adrienne Karpiel ◽  
Mihai Covasa ◽  
Robert C. Ritter
Keyword(s):  
Cytosolic Calcium ◽  
Threshold Concentration ◽  
Extracellular Calcium ◽  
Calcium Stores ◽  
Afferent Neurons ◽  
Sensory Stimuli ◽  
Adult Rat ◽  
Nodose Ganglia ◽  
Vagal Afferent ◽  
High Concentrations

Imaging fluorescent measurements with fura 2 were used to examine cytosolic calcium signals induced by sulfated CCK octapeptide (CCK-8) in dissociated vagal afferent neurons from adult rat nodose ganglia. We found that 40% (184/465) of the neurons responded to CCK-8 with a transient increase in cytosolic calcium. The threshold concentration of CCK-8 for inducing the response varied from 0.01 to 100 nM. In most neurons (13/16) the response was eliminated by removing extracellular calcium. Depleting intracellular calcium stores with thapsigargin slightly augmented the response. Most neurons were unresponsive to nonsulfated CCK-8. The response was eliminated by the CCK-A receptor antagonist lorglumide. Low concentrations of JMV-180 had no effect; however, high concentrations of JMV-180 reduced responses to CCK-8. These results demonstrate that CCK acts at the low-affinity site of the CCK-A receptor to trigger the entry of extracellular calcium into vagal afferent neurons. Increased cytosolic calcium may participate in acute activation of vagal afferent neurons, or it may initiate long-term changes, which modulate future neuronal responses to sensory stimuli.

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.

scholarly journals Expression of transient receptor potential channels and two-pore potassium channels in subtypes of vagal afferent neurons in rat

2010 ◽  
Vol 298 (2) ◽  
pp. G212-G221 ◽  
Author(s):  
Huan Zhao ◽  
Leslie K. Sprunger ◽  
Steven M. Simasko
Keyword(s):  
Single Cell ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Vagal Afferents ◽  
Afferent Neurons ◽  
Single Cell Pcr ◽  
Nodose Ganglia ◽  
Vagal Afferent ◽  
Transient Receptor

Vagal afferent neurons relay important information regarding the control of the gastrointestinal system. However, the ionic mechanisms that underlie vagal activation induced by sensory inputs are not completely understood. We postulate that transient receptor potential (TRP) channels and/or two-pore potassium (K2p) channels are targets for activating vagal afferents. In this study we explored the distribution of these channels in vagal afferents by quantitative PCR after a capsaicin treatment to eliminate capsaicin-sensitive neurons, and by single-cell PCR measurements in vagal afferent neurons cultured after retrograde labeling from the stomach or duodenum. We found that TRPC1/3/5/6, TRPV1-4, TRPM8, TRPA1, TWIK2, TRAAK, TREK1, and TASK1/2 were all present in rat nodose ganglia. Both lesion results and single-cell PCR results suggested that TRPA1 and TRPC1 were preferentially expressed in neurons that were either capsaicin sensitive or TRPV1 positive. Expression of TRPM8 varied dynamically after various manipulations, which perhaps explains the disparate results obtained by different investigators. Last, we also examined ion channel distribution with the A-type CCK receptor (CCK-RA) and found there was a significant preference for neurons that express TRAAK to also express CCK-RA, especially in gut-innervating neurons. These findings, combined with findings from prior studies, demonstrated that background conductances such as TRPC1, TRPA1, and TRAAK are indeed differentially distributed in the nodose ganglia, and not only do they segregate with specific markers, but the degree of overlap is also dependent on the innervation target.

Localization and functional effects of adenosine A1 receptors on cardiac vagal afferents in adult rats

1998 ◽  
Vol 274 (2) ◽  
pp. H441-H447 ◽  
Author(s):  
Holly R. Middlekauff ◽  
Scott A. Rivkees ◽  
Helen E. Raybould ◽  
Melo Bitticaca ◽  
Joshua I. Goldhaber ◽  
...  
Keyword(s):  
Adenosine Receptors ◽  
Nodose Ganglion ◽  
Vagal Afferents ◽  
Afferent Neurons ◽  
Adult Rats ◽  
Nodose Ganglia ◽  
Complementary Approach ◽  
Cardiac Nociception ◽  
Vagal Afferent ◽  
Ganglion Neurons

There is evidence to suggest that during ischemia adenosine acts on cardiac vagal afferent neurons to activate systemic reflexes and to modulate cardiac nociception. The purpose of this study was to determine whether adenosine receptors are present and have direct cellular electrophysiological actions on cardiac vagal afferent neurons. In radioreceptor assays of nodose ganglion tissue from rats, binding was detectable for A1 (39.6 ± 1.2 fmol/mg protein) but not A2aadenosine receptors. These findings were confirmed using the complementary approach of receptor-labeling autoradiography. Using in situ hybridization, we saw specific labeling over ∼50% of neurons in the nodose ganglia, but not over nonneuronal cells. In colabeling studies, cardiac vagal afferent neurons were identified by retroneuronal labeling with fluororuby. Of cardiac vagal afferents approximately one-half were strongly positive for A1 adenosine receptors (immunocytochemistry). In patch-clamping experiments, adenosine inhibited peak inward calcium current in 7 of 11 cells by 48 ± 13%. In conclusion, adenosine A1receptors reside on a subset of vagal afferent neurons, including cardiac vagal afferents, and have electrophysiological effects that modulate neuroexcitability in cultured nodose ganglion neurons.

Effect of calcium on transport characteristics of cultured proximal renal cells

1985 ◽  
Vol 249 (3) ◽  
pp. F346-F355
Author(s):  
L. M. Sakhrani ◽  
N. Tessitore ◽  
S. G. Massry
Keyword(s):  
Phosphate Uptake ◽  
Cytosolic Calcium ◽  
Ruthenium Red ◽  
Extracellular Calcium ◽  
Transport Processes ◽  
Renal Cells ◽  
Sodium Uptake ◽  
Calcium Loading ◽  
Sodium Dependent ◽  
Acute Changes

We examined the effects of acute changes in extracellular and intracellular calcium on transport processes in primary culture of proximal rabbit renal cells. A change in extracellular calcium from 0 to 3 mM inhibited amiloride-sensitive sodium uptake by 30%, and this effect was maximal at 1 mM calcium. Other polyvalent cations (Mn2+, Mg2+, La3+, and Ba2+) produced quantitatively similar inhibition of amiloride-sensitive sodium uptake compared with calcium. An increase in cytosolic calcium produced by calcium loading (20 mM) or by A23187 (20 microM) resulted in an inhibition of 25-40% of amiloride-sensitive sodium uptake. Moreover, quinidine (10(-4)M) and ruthenium red (3 microM), agents presumed to increase cytosolic calcium, inhibited amiloride-sensitive sodium uptake by 20-60%. Both these agents also inhibited sodium-dependent phosphate uptake by 20% but had no effect on ouabain-sensitive 86Rb+ uptake or on sodium-dependent alpha-methylglucoside uptake. Our data indicate that increases in extracellular calcium inhibit amiloride-sensitive sodium uptake and increases in cytosolic calcium inhibit sodium-dependent phosphate and amiloride-sensitive sodium uptakes. The effect of extracellular calcium may be due to charge screening and/or binding to the negatively charged plasma membrane or due to alterations in membrane fluidity.

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.

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.

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.

scholarly journals Role of Transient Receptor Potential Channels in Cholecystokinin-Induced Activation of Cultured Vagal Afferent Neurons

Endocrinology ◽  
2010 ◽  
Vol 151 (11) ◽  
pp. 5237-5246 ◽  
Author(s):  
Huan Zhao ◽  
Steven M. Simasko
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Cytosolic Calcium ◽  
Membrane Depolarization ◽  
Induced Response ◽  
Trpc Channels ◽  
Afferent Neurons ◽  
Trpv Channels ◽  
Vagal Afferent ◽  
Transient Receptor

Cholecystokinin (CCK), an endogenous brain-gut peptide, is released after food intake and promotes the process of satiation via activation of the vagus nerve. In vitro, CCK increases cytosolic calcium concentrations and produces membrane depolarization in a subpopulation of vagal afferent neurons. However, the specific mechanisms and ionic conductances that mediate these effects remain unclear. In this study we used calcium imaging, electrophysiological measurements, and single cell PCR analysis on cultured vagal afferent neurons to address this issue directly. A cocktail of blockers of voltage-dependent calcium channels (VDCC) failed to block CCK-induced calcium responses. In addition, SKF96365, a compound that blocks both VDCC and the C family of transient receptor potential (TRP) channels, also failed to prevent responses to CCK. Together these results suggest that CCK-induced calcium influx is not subsequent to the membrane depolarization. Ruthenium red, an inhibitor of the TRPV family and TRPA1, blocked both depolarizing responses to CCK and CCK-induced calcium increases, but had no effect on the KCl-induced calcium response. Selective block of TRPV1 and TRPA1 channels with SB366791 and HC030031, respectively, had minor effects on the CCK-induced response. Application of 2-aminoethoxydiphenyl borate, an activator of select TRPV channels but a blocker of several TRPC channels, either had no effect or enhanced the responses to CCK. Further, results from PCR experiments revealed a significant clustering of TRPV2-5 in neurons expressing CCK1 receptors. These observations demonstrate that CCK-induced increases in cytosolic calcium and membrane depolarization of vagal afferent neurons are likely mediated by TRPV channels, excluding TRPV1.

II. Integration of afferent signaling from the viscera by the nodose ganglia

2003 ◽  
Vol 284 (1) ◽  
pp. G8-G14 ◽  
Author(s):  
Kirsteen N. Browning ◽  
David Mendelowitz
Keyword(s):  
Sensory Neurons ◽  
Tissue Injury ◽  
Large Body ◽  
Sensory Function ◽  
Afferent Neurons ◽  
Nodose Ganglia ◽  
Vagal Afferent ◽  
Afferent Signaling ◽  
Recent Demonstration ◽  
Stimulation Of

To understand vago-vagal reflexes, one must have an appreciation of the events surrounding the encoding, integration, and central transfer of peripheral sensations by vagal afferent neurons. A large body of work has shown that vagal afferent neurons have nonuniform properties and that distinct subpopulations of neurons exist within the nodose ganglia. These sensory neurons display a considerable degree of plasticity; electrophysiological, pharmacological, and neurochemical properties have all been shown to alter after peripheral tissue injury. The validity of claims of selective recordings from populations of neurons activated by peripheral stimuli may be diminished, however, by the recent demonstration that stimulation of a subpopulation of nodose neurons can enhance the activity of unstimulated neuronal neighbors. To better understand the neurophysiological processes occurring after vagal afferent stimulation, it is essential that the electrophysiological, pharmacological, and neurochemical properties of nodose neurons are correlated with their sensory function or, at the very least, with their specific innervation target.

Sign in / Sign up

Export Citation Format

Share Document