Ghrelin acts on the dorsal vagal complex to stimulate pancreatic protein secretion

2006 ◽  
Vol 290 (6) ◽  
pp. G1350-G1358 ◽  
Author(s):  
Ying Li ◽  
Xiaoyin Wu ◽  
Ying Zhao ◽  
Shengliang Chen ◽  
Chung Owyang
Keyword(s):  
Brain Stem ◽  
Protein Secretion ◽  
Intravenous Infusion ◽  
Pancreatic Secretion ◽  
Area Postrema ◽  
Fold Increase ◽  
Motor Nucleus ◽  
Dorsal Motor Nucleus ◽  
Selective Ablation

Ghrelin receptors are present in the central nervous system. We hypothesized that ghrelin released from the stomach acts as an endocrine substance and stimulates brain stem vagovagal circuitry to evoke pancreatic secretion. In an in vivo anesthetized rat model, an intravenous infusion of ghrelin at doses of 5, 10, and 25 nmol increased pancreatic protein secretion from a basal level of 125 ± 6 to 186 ± 8, 295 ± 12, and 356 ± 11 mg/h, respectively. Pretreatment with atropine or hexamethonium or an acute vagotomy, but not a perivagal application of capsaicin, completely abolished pancreatic protein secretion responses to ghrelin. In conscious rats, an intravenous infusion of ghrelin at a dose of 10 nmol resulted in a 2.2-fold increase in pancreatic protein secretion over basal volume. Selective ablation of the area postrema abolished pancreatic protein secretion stimulated by intravenous infusion of ghrelin but did not alter the increase in pancreatic protein secretion evoked by diversion of bile-pancreatic juice. Immunohistochemical staining showed a marked increase in the number of c-Fos-expressing neurons in the area postrema, nucleus of the solitary tract, and dorsal motor nucleus of the vagus after an intravenous infusion of ghrelin in sham-lesioned rats; selective ablation of the area postrema eliminated this increase. In conclusion, ghrelin stimulates pancreatic secretion via a vagal cholinergic efferent pathway. Circulating ghrelin gains access to the brain stem vagovagal circuitry via the area postrema, which represents the primary target on which peripheral ghrelin may act as an endocrine substance to stimulate pancreatic secretion.

Δ9-Tetrahydrocannabinol selectively acts on CB1 receptors in specific regions of dorsal vagal complex to inhibit emesis in ferrets

2003 ◽  
Vol 285 (3) ◽  
pp. G566-G576 ◽  
Author(s):  
Marja D. Van Sickle ◽  
Lorraine D. Oland ◽  
Ken Mackie ◽  
Joseph S. Davison ◽  
Keith A. Sharkey
Keyword(s):  
Receptor Antagonist ◽  
Brain Stem ◽  
Area Postrema ◽  
Motor Nucleus ◽  
Cb1 Receptors ◽  
Dorsal Vagal Complex ◽  
Dorsal Motor Nucleus ◽  
Site Of Action ◽  
Fos Expression ◽  
The Brain

The aim of this study was to investigate the efficacy, receptor specificity, and site of action of Δ9-tetrahydrocannabinol (THC) as an antiemetic in the ferret. THC (0.05-1 mg/kg ip) dose-dependently inhibited the emetic actions of cisplatin. The ED50 for retching was ∼0.1 mg/kg and for vomiting was 0.05 mg/kg. A specific cannabinoid (CB)1 receptor antagonist SR-141716A (5 mg/kg ip) reversed the effect of THC, whereas the CB2 receptor antagonist SR-144528 (5 mg/kg ip) was ineffective. THC applied to the surface of the brain stem was sufficient to inhibit emesis induced by intragastric hypertonic saline. The site of action of THC in the brain stem was further assessed using Fos immunohistochemistry. Fos expression induced by cisplatin in the dorsal motor nucleus of the vagus (DMNX) and the medial subnucleus of the nucleus of the solitary tract (NTS), but not other subnuclei of the NTS, was significantly reduced by THC rostral to obex. At the level of the obex, THC reduced Fos expression in the area postrema and the dorsal subnucleus of the NTS. The highest density of CB1 receptor immunoreactivity was found in the DMNX and the medial subnucleus of the NTS. Lower densities were observed in the area postrema and dorsal subnucleus of the NTS. Caudal to obex, there was moderate density of staining in the commissural subnucleus of the NTS. These results show that THC selectively acts at CB1 receptors to reduce neuronal activation in response to emetic stimuli in specific regions of the dorsal vagal complex.

PYY inhibits CCK-stimulated pancreatic secretion through the area postrema in unanesthetized rats

2001 ◽  
Vol 281 (2) ◽  
pp. R645-R653 ◽  
Author(s):  
Xiaoying Deng ◽  
Dulce R. Guarita ◽  
Martha R. A. Pedroso ◽  
Christianna Kreiss ◽  
Paul G. Wood ◽  
...  
Keyword(s):  
Protein Secretion ◽  
Pancreatic Juice ◽  
Pancreatic Secretion ◽  
Peptide Yy ◽  
Area Postrema ◽  
Pancreatic Fluid ◽  
Vagal Pathway ◽  
Dependent Mechanism

Peptide YY (PYY) inhibits CCK-8-secretin-stimulated pancreatic secretion in vivo. To investigate whether CCK-8-secretin-stimulated pancreatic secretion is mediated through a vago-vagal pathway and whether PYY inhibits this pathway through the area postrema (AP), chronic pancreatic, biliary, and duodenal catheters were implanted in AP-lesioned (APX) or sham-operated rats. The effects of APX on pancreatic secretion stimulated by bethanechol, pancreatic juice diversion (PJD), or CCK-8-secretin, were tested, with and without background PYY infusion, in unanesthetized rats. APX reduced basal pancreatic secretion by 15–20% ( P < 0.01). APX had no effect on bethanechol-stimulated secretion and potentiated protein secretion stimulated by PJD (396 vs. 284%) and exogenous CCK-8-secretin. In sham-operated rats, background PYY potently inhibited CCK-8-secretin-stimulated pancreatic fluid (1.8 vs. 48.2%) and protein secretion (3.7 vs. 45.8%) but potentiated fluid (52.9 vs. 43.1%) and protein (132.9 vs. 68.9%) secretion in APX rats. Our findings demonstrate that PYY inhibits CCK-8-secretin-stimulated pancreatic secretion through an AP-dependent mechanism in sham-operated rats. The AP also contributes to basal pancreatic secretion.

scholarly journals Respiratory dysfunction following neonatal sustained hypoxia exposure during a critical window of brain stem extracellular matrix formation

2018 ◽  
Vol 314 (2) ◽  
pp. R216-R227 ◽  
Author(s):  
C. Stryker ◽  
D. W. Camperchioli ◽  
C. A. Mayer ◽  
W. J. Alilain ◽  
R. J. Martin ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Brain Stem ◽  
Nucleus Tractus Solitarius ◽  
Area Postrema ◽  
Brain Maturation ◽  
Motor Nucleus ◽  
Perineuronal Net ◽  
Cardiorespiratory Control ◽  
Dorsal Motor Nucleus ◽  
Control Regions

The extracellular matrix (ECM) modulates brain maturation and plays a major role in regulating neuronal plasticity during critical periods of development. We examined 1) whether there is a critical postnatal period of ECM expression in brain stem cardiorespiratory control regions and 2) whether the attenuated hypoxic ventilatory response (HVR) following neonatal sustained (5 days) hypoxia [SH (11% O2, 24 h/day)] exposure is associated with altered ECM formation. The nucleus tractus solitarius (nTS), dorsal motor nucleus of the vagus, hypoglossal motor nucleus, cuneate nucleus, and area postrema were immunofluorescently processed for aggrecan and Wisteria floribunda agglutinin (WFA), a key proteoglycan of the ECM and the perineuronal net. From postnatal day ( P) 5 ( P5), aggrecan and WFA expression increased postnatally in all regions. We observed an abrupt increase in aggrecan expression in the nTS, a region that integrates and receives afferent inputs from the carotid body, between P10 and P15 followed by a distinct and transient plateau between P15 and P20. WFA expression in the nTS exhibited an analogous transient plateau, but it occurred earlier (between P10 and P15). SH between P11 and P15 attenuated the HVR (assessed at P16) and increased aggrecan (but not WFA) expression in the nTS, dorsal motor nucleus of the vagus, and area postrema. An intracisternal microinjection of chondroitinase ABC, an enzyme that digests chondroitin sulfate proteoglycans, rescued the HVR and the increased aggrecan expression. These data indicate that important stages of ECM formation take place in key brain stem respiratory neural control regions and appear to be associated with a heightened vulnerability to hypoxia.

scholarly journals Differential organization of excitatory and inhibitory synapses within the rat dorsal vagal complex

2011 ◽  
Vol 300 (1) ◽  
pp. G21-G32 ◽  
Author(s):  
Tanja Babic ◽  
Kirsteen N. Browning ◽  
R. Alberto Travagli
Keyword(s):  
Brain Stem ◽  
Pancreatic Secretion ◽  
Firing Frequency ◽  
Inhibitory Synapses ◽  
Motor Nucleus ◽  
Glutamatergic Synapses ◽  
Dorsal Motor Nucleus ◽  
Whole Cell Patch Clamp ◽  
The Brain ◽  
Upper Gastrointestinal

The dorsal motor nucleus of the vagus (DMV) is pivotal in the regulation of upper gastrointestinal functions, including motility and both gastric and pancreatic secretion. DMV neurons receive robust GABA- and glutamatergic inputs. Microinjection of the GABAA antagonist bicuculline (BIC) into the DMV increases pancreatic secretion and gastric motility, whereas the glutamatergic antagonist kynurenic acid (KYN) is ineffective unless preceded by microinjection of BIC. We used whole cell patch-clamp recordings with the aim of unveiling the brain stem neurocircuitry that uses tonic GABA- and glutamatergic synapses to control the activity of DMV neurons in a brain stem slice preparation. Perfusion with BIC altered the firing frequency of 71% of DMV neurons, increasing firing frequency in 80% of the responsive neurons and decreasing firing frequency in 20%. Addition of KYN to the perfusate either decreased (52%) or increased (25%) the firing frequency of BIC-sensitive neurons. When KYN was applied first, the firing rate was decreased in 43% and increased in 21% of the neurons; further perfusion with BIC had no additional effect in the majority of neurons. Our results indicate that there are several permutations in the arrangements of GABA- and glutamatergic inputs controlling the activity of DMV neurons. Our data support the concept of brain stem neuronal circuitry that may be wired in a finely tuned organ- or function-specific manner that permits precise and discrete modulation of the vagal motor output to the gastrointestinal tract.

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.

scholarly journals Postnatal developmental expressions of neurotransmitters and receptors in various brain stem nuclei of rats

2005 ◽  
Vol 98 (4) ◽  
pp. 1442-1457 ◽  
Author(s):  
Qiuli Liu ◽  
Margaret T. T. Wong-Riley
Keyword(s):  
Brain Stem ◽  
Respiratory Control ◽  
Nucleus Ambiguus ◽  
Hypoglossal Nucleus ◽  
Motor Nucleus ◽  
Developmental Trend ◽  
Receptor Subunit ◽  
Cuneate Nucleus ◽  
Glycine Receptors ◽  
Dorsal Motor Nucleus

Previously, we reported that the expression of cytochrome oxidase in a number of brain stem nuclei exhibited a plateau or reduction at postnatal day (P) 3–4 and a dramatic decrease at P12, against a general increase with age. The present study examined the expression of glutamate, N-methyl-d-aspartate receptor subunit 1 (NMDAR1), GABA, GABAB receptors, glycine receptors, and glutamate receptor subunit 2 (GluR2) in the ventrolateral subnucleus of the solitary tract nucleus, nucleus ambiguus, hypoglossal nucleus, medial accessory olivary nucleus, dorsal motor nucleus of the vagus, and cuneate nucleus, from P2 to P21 in rats. Results showed that 1) the expression of glutamate increased with age in a majority of the nuclei, whereas that of NMDAR1 showed heterogeneity among the nuclei; 2) GABA and GABAB expressions decreased with age, whereas that of glycine receptors increased with age; 3) GluR2 showed two peaks, at P3–4 and P12; and 4) glutamate and NMDAR1 showed a significant reduction, whereas GABA, GABAB receptors, glycine receptors, and GluR2 exhibited a concomitant increase at P12. These features were present but less pronounced in hypoglossal nucleus and dorsal motor nucleus of the vagus and were absent in the cuneate nucleus. These data suggest that brain stem nuclei, directly or indirectly related to respiratory control, share a common developmental trend with the pre-Bötzinger complex in having a transient period of imbalance between inhibitory and excitatory drives at P12. During this critical period, the respiratory system may be more vulnerable to excessive exogenous stressors.

Galanin Inhibits Gut-Related Vagal Neurons in Rats

2004 ◽  
Vol 91 (5) ◽  
pp. 2330-2343 ◽  
Author(s):  
Zhenjun Tan ◽  
Ronald Fogel ◽  
Chunhui Jiang ◽  
Xueguo Zhang
Keyword(s):  
Potassium Channel ◽  
Reversal Potential ◽  
Outward Current ◽  
Motor Nucleus ◽  
Dorsal Vagal Complex ◽  
Solitary Tract ◽  
Membrane Hyperpolarization ◽  
Dorsal Motor Nucleus

Galanin plays an important role in the regulation of food intake, energy balance, and body weight. Many galanin-positive fibers as well as galanin-positive neurons were seen in the dorsal vagal complex, suggesting that galanin produces its effects by actions involving vagal neurons. In the present experiment, we used tract-tracing and neurophysiological techniques to evaluate the origin of the galaninergic fibers and the effect of galanin on neurons in the dorsal vagal complex. Our results reveal that the nucleus of the solitary tract is the major source of the galanin terminals in the dorsal vagal complex. In vivo experiments demonstrated that galanin inhibited the majority of gut-related neurons in the dorsal motor nucleus of the vagus. In vitro experiments demonstrated that galanin inhibited the majority of stomach-projecting neurons in the dorsal motor nucleus of the vagus by suppressing spontaneous activity and/or producing a fully reversible dose-dependent membrane hyperpolarization and outward current. The galanin-induced hyperpolarization and outward current persisted after synaptic input was blocked, suggesting that galanin acts directly on receptors of neurons in the dorsal motor nucleus of the vagus. The reversal potential induced by galanin was close to the potassium ion potentials of the Nernst equation and was prevented by the potassium channel blocker tetraethylammonium, indicating that the inhibitory effect of galanin was mediated by a potassium channel. These results indicate that the dorsal motor nucleus of the vagus is inhibited by galanin derived predominantly from neurons in the nucleus of the solitary tract projecting to the dorsal motor nucleus of the vagus nerve. Galanin is one of the neurotransmitters involved in the vago-vagal reflex.

Studies of the Central Neural Pathways to the Stomach and Zusanli (ST36)

2001 ◽  
Vol 29 (02) ◽  
pp. 211-220 ◽  
Author(s):  
Chang Hyun Lee ◽  
Han Sol Jung ◽  
Tae Young Lee ◽  
Sang Ryoung Lee ◽  
Sang Won Yuk ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Vagus Nerve ◽  
Nucleus Tractus Solitarius ◽  
Area Postrema ◽  
Reticular Nucleus ◽  
Hypothalamic Nucleus ◽  
Cell Group ◽  
Motor Nucleus ◽  
Amygdaloid Nucleus ◽  
Dorsal Motor Nucleus

The purpose of this morphological study was to investigate the relation between the meridian, meridian points and viscera using neuroanatomical tracers. The common locations of the spinal cord and brain projecting to the stomach and Zusanli were observed following injection of CTB (cholera toxin B subunit) and pseudorabies viruses (PRV-Ba, Bartha strain and PRV-Ba-Gal, galactosidase insertion) into the stomach and Zusanli (ST36). After 4–5 days of survival following injection into twelve rats, they were perfused, and their spinal cords and brains were frozen sectioned (30 μm). These sections were stained by X-gal histochemical, CTB and PRV-Bia immunohistochemical staining methods, and examined with the light microscope. The results were as follows: Commonly labeled medulla oblongata regions were dorsal motor nucleus of vagus nerve (DMV), nucleus tractus solitarius (NTS) and area postrema (AP) following injection of CTB and PRV-Ba-Gal into stomach and Zusanli, respectively. In the spinal cord, commonly labeled neurons were found in thoracic, lumbar and sacral spinal segments. Densely labeled areas were found in lamina IV, V, VII (intermediolateral nucleus) and X of the spinal cord. In the brain, commonly labeled neurons were found in the A1 noradrenalin cells/C1 adrenalin cells/caudoventrolateral reticular nucleus, dorsal motor nucleus of vagus nerve, nucleus tractus solitarius, area postrema, raphe obscurus nucleus, raphe pallidus nucleus, raphe magnus nucleus, gigantocellular nucleus, locus coeruleus, parabrachial nucleus, Kolliker-Fuse nucleus, A5 cell group, central gray matter, paraventricular hypothalamic nucleus, lateral hypothalamic nucleus, retrochiasmatic hypothalamic nucleus, bed nucleus of stria terminals and amygdaloid nucleus. Thus central autonomic center project both to the stomach and Zusanli. These morphological results suggest that there is a commonality of CNS cell groups in brain controlling stomach (viscera) and Zusanli (limb).

Distribution of α2-Adrenergic Receptor Binding in the Developing Human Brain Stem

2001 ◽  
Vol 4 (3) ◽  
pp. 222-236 ◽  
Author(s):  
Jaleh Mansouri ◽  
Ashok Panigrahy ◽  
Susan F. Assmann ◽  
Hannah C. Kinney
Keyword(s):  
Brain Stem ◽  
Reticular Formation ◽  
Inferior Olive ◽  
Human Life ◽  
Motor Nucleus ◽  
Solitary Tract ◽  
Medullary Reticular Formation ◽  
Cardiorespiratory Control ◽  
Dorsal Motor Nucleus ◽  
Early Human

Rapid and dramatic changes occur in cardiorespiratory function during early human life. Catecholamines within select brain stem nuclei are implicated in the control of autonomic and respiratory function, including in the nucleus of the solitary tract and the dorsal motor nucleus of X. Animal and adult human studies have shown high binding to α2-adrenergic receptors in these regions. To determine the developmental profile of brainstem α2-adrenergic binding across early human life, we studied brain stems from five fetuses at mid-gestation, three newborns (37–38 postconceptional weeks), and six infants (44–61 postconceptional weeks). We used quantitative tissue receptor autoradiography with [3H]para-aminoclonidine as the radioligand and phentolamine as the displacer. In the fetal group, binding was high (63–93 fmol/mg tissue) in the nucleus of the solitary tract, dorsal motor nucleus of X, locus coeruleus, and reticular formation; it was low (<32 fmol/mg tissue) in the principal inferior olive and basis pontis. Binding decreased in all regions with age: in infancy, the highest binding was in the intermediate range (32–62 fmol/mg tissue) and was localized to the nucleus of the solitary tract and dorsal motor nucleus of X. The most substantial decrease in binding (75%–85%) between the fetal and infant periods occurred in the pontine and medullary reticular formation and hypoglossal nucleus. Binding remained low in the principal inferior olive and basis pontis. The decreases in binding with age remained significant after quench correction. These data suggest that rapid and dramatic changes occur in early human life in the brain stem catecholaminergic system in regions related to cardiorespiratory control.

PYY in brain stem nuclei induces vagal stimulation of gastric acid secretion in rats

1995 ◽  
Vol 268 (6) ◽  
pp. G943-G948 ◽  
Author(s):  
H. Yang ◽  
Y. Tache
Keyword(s):  
Acid Secretion ◽  
Brain Stem ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Serotonin Receptor ◽  
Peptide Yy ◽  
Motor Nucleus ◽  
Dorsal Motor Nucleus ◽  
Raphe Pallidus ◽  
Stimulation Of

The influence of peptide YY (PYY) microinjected into brain stem nuclei on gastric acid secretion (GAS) was investigated in urethan-anesthetized rats with gastric cannula. PYY (30-200 ng) microinjected into the dorsal motor nucleus of the vagus (DMN) induces a dose-related and vagal-dependent stimulation of GAS (net increase from 13 +/- 4 to 59 +/- 12 mumol/90 min). PYY (200 ng) injected intravenously intracisternally into sites adjacent to the DMN had no effect. GAS induced by PYY into the DMN was potentiated by coinjection of thyrotropin-releasing hormone (TRH, 30 ng) or the serotonin receptor (5-HT2) agonist (+/-)-1-(4-methyl-1-piperazinyl)-pyrrolo(1,2-a)quinoxaline (357 ng) and by microinjection of kainic acid (1 ng) into the raphe pallidus. Prepro-TRH-(160-169) (200 ng into the DMN) did not influence the stimulatory effect of PYY. PYY (200 ng) microinjected into the raphe pallidus, raphe obscurus, and nucleus ambiguous also increased GAS, although the response was of shorter duration than that in the DMN. These results indicate that PYY acts in brain stem nuclei involved in the vagal regulation of GAS and that PYY action in the DMN is potentiated by TRH or 5-HT2 receptor agonist acting at this site.

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