Visceral hypersensitivity is common in patients with irritable bowel syndrome (IBS). We investigated whether inflammatory molecules, such as histamine and proteases, activate prostaglandin-endoperoxide synthase 2 (also called COX2) to increase the synthesis of prostaglandin E2 (PGE2) by mast cells, which activates receptor PTGER2 EP2) dorsal root ganglia promote visceral hypersensitivity.We used an enzyme-linked immunosorbent assay measure levels spontaneous release molecules from cells...

Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) are carbohydrates thought to contribute the symptoms of IBS. A diet in high FODMAPs (HFM) induces gastrointestinal patients with irritable bowel syndrome (IBS), a low (LFM) improves up 60% However, mechanism by which affect IBS is unclear. We showed that mice fed on HFM have mast cell activation colonic barrier loss. Using cell-deficient without reconstitution, we HFM-mediated loss dependent TLR4-dependent...

The vagal afferent system is strategically positioned to mediate rapid changes in motility and satiety response systemic glucose levels. In the present study we aimed identify glucose-excited glucose-inhibited neurons nodose ganglia characterize their glucose-sensing properties. Whole-cell patch-clamp recordings isolated from rat demonstrated that 31/118 (26%) were depolarized after increasing extracellular 5 15 mm; 19/118 (16%) hyperpolarized, 68/118 non-responsive. A higher incidence of...

Research has shown that the synergistic interaction between vagal cholecystokinin-A receptors (CCKARs) and leptin (LRbs) mediates short term satiety. We hypothesize this is mediated by cross-talk signaling cascades used CCKARs LRbs, which, in turn, activates closure of K+ channels, leading to membrane depolarization neuronal firing. Whole cell patch clamp recordings were performed on isolated rat nodose ganglia neurons. Western immunoblots elucidated intracellular pathways modulate...

Orexin (hypocretin)‐containing projections from lateral hypothalamus (LH) are thought to play an important role in the regulation of feeding behaviour and energy balance. In rodent studies, central administration orexin peptides increases food intake, neurones LH activated by hypoglycaemia during fasting. addition, orexins into fourth ventricle or dorsal motor nucleus vagus (DMV) has been shown stimulate gastric acid secretion motility, respectively, via vagal efferent pathways. this study,...

1. Whole cell recordings from neurons in the rostral, gustatory nucleus of solitary tract (rNST) were made using "blind" patch-clamp technique horizontal brain stem slices rats. 2. Postsynaptic potentials (PSP) elicited 71 rNST by electrical stimulation (ST). To investigate PSPs evoked convergent input chorda tympani and glossopharyngeal nerves, ST was stimulated at levels where these two nerves terminate. These are referred to as rostral (rST) intermediate (iST) ST, respectively. 3. When...

<h3>Objective</h3> Increased faecal butyrate levels have been reported in irritable bowel syndrome. Rectal instillation of sodium (NaB) increases visceral sensitivity rats by an unknown mechanism. We seek to examine the signal transduction pathways responsible for enhanced neuronal excitability dorsal root ganglion (DRG) following NaB enemas and demonstrate that this is colonic hypersensitivity animal model. <h3>Design</h3> Colorectal distention (CRD) studies were performed treated with...

The differentiation of fibroblasts into myofibroblasts is critical for the development fibrotic disorders, including idiopathic pulmonary fibrosis (IPF). Previously, we demonstrated that from patients with IPF exhibit changes in DNA methylation across genome contribute to a profibrotic phenotype. One top differentially methylated genes identified our previous study was KCNMB1, which codes β subunit large-conductance potassium (BK, also known as MaxiK or KCa1.1) channel. Here, examined how...

Vagal CCK-A receptors (CCKARs) and leptin (LRbs) interact synergistically to mediate short-term satiety. Cocaine- amphetamine-regulated transcript (CART) peptide is expressed by vagal afferent neurons. We sought demonstrate that this neurotransmitter regulates CCK actions on also examined the signal transduction pathways responsible for mediating CART release from nodose ganglia (NG). ELISA studies coupled with gene silencing of NG neurons RNA interference elucidated intracellular signaling...

OBJECTIVE Diabetic patients often experience visceral hypersensitivity and anorectal dysfunction. We hypothesize that the enhanced excitability of colon projecting dorsal root ganglia (DRG) neurons observed in diabetes is caused by a decrease amplitude transient A-type K+ (IA) currents resulting from increased phosphorylation mitogen-activated protein kinases (MAPK) reduced opening Kv4.2 channels. RESEARCH DESIGN AND METHODS performed patch-clamp recordings DRG control streptozotocin-induced...

Key points Ghrelin, a hunger signalling peptide derived from the peripheral tissues, overcomes satiety signals evoked by anorexigenic molecules, such as cholecystokinin (CCK) and leptin, to stimulate feeding. Using in vivo vitro electrophysiological techniques, we show that ghrelin hyperpolarizes neurons inhibits currents leptin CCK‐8. Administering K ATP channel antagonist or silencing Kir6.2, major subunit of channel, abolished inhibition. The inhibitory actions were also treating vagal...

Hippocampal pyramidal neurones display a Ca(2+)-dependent K(+) current responsible for the slow afterhyperpolarization (I(sAHP)), prominent regulator of excitability. There is considerable transmitter convergence onto I(sAHP) but little information about interplay between kinase-based transduction mechanisms underlying action. We have added to existing role protein kinase C (PKC) in kainate receptor actions by demonstrating that direct postsynaptic activation PKC with either...

Abstract The anorexigenic adipocyte-derived hormone leptin and the orexigenic ghrelin act in opposition to regulate feeding behavior via vagal afferent pathways. mechanisms by which exerts its inhibitory effects on are unknown. We hypothesized that activates exchange protein activated cAMP (Epac), inducing increased SOCS3 expression, negatively affects signal transduction neuronal firing nodose ganglia (NG) neurons. showed 91 ± 3% of receptor (LRb) –bearing neurons contained receptors...

Grabauskas, Gintautas and Robert M. Bradley. Tetanic stimulation induces short-term potentiation of inhibitory synaptic activity in the rostral nucleus solitary tract. J. Neurophysiol. 79: 595–604, 1998. Whole cell recordings from neurons tract (rNST) were made to explore effect high-frequency tetanic on postsynaptic potentials (IPSPs). IPSPs elicited rNST by local electrical after pharmacological blockade excitatory transmission. at frequencies 10–30 Hz resulted sustained hyperpolarizing...

Sensitization of esophageal afferents plays an important role in nociception, but the mechanism is less clear. Our previous studies demonstrated that mast cell (MC) activation releases preformed mediators histamine and tryptase, which play roles sensitization vagal nociceptive C fibers. PGD2 a lipid mediator released by activated MCs. Whether this process has yet to be determined. Expression DP1 DP2 receptors nodose ganglion neurons was determined immunofluorescence staining, Western...

Prolactin‐releasing peptide (PrRP) is a recently discovered neuropeptide implicated in the central control of feeding behaviour and autonomic homeostasis. PrRP‐containing neurones PrRP receptor mRNA are found abundance caudal portion nucleus tractus solitarius (NTS), an area which together with dorsal motor vagus (DMV) comprises integrated structure, vagal complex (DVC) that processes visceral afferent signals from provides parasympathetic innervation to gastrointestinal tract. In this...

Glucosensing nodose ganglia neurons mediate the effects of hyperglycemia on gastrointestinal motility. We hypothesized that glucose-sensing mechanisms in are similar to those hypothalamic glucose excited neurons, which sense through glycolysis. Glucose metabolism leads ATP-sensitive potassium channel (KATP) closure and membrane depolarization. identified glucosensing elements form transporters (GLUTs), glucokinase (GK), KATP channels rat evaluated their physiological significance. In vitro...

To explore the postnatal development of inhibitory synaptic activity in rostral (gustatory) nucleus solitary tract (rNST), whole cell and gramicidin perforated patch-clamp recordings were made five age groups rats [ day 0–7 ( P0–7), P8–14, P15–21, P22–30, P &gt; 55]. The passive membrane properties developing rNST neurons as well electrophysiological pharmacological characteristics single tetanic stimulus-evoked postsynaptic potentials (IPSPs) studied brain slices under glutamate receptor...

To explore the parameters that define characteristics of either inhibitory postsynaptic potentials (IPSP) or currents (IPSC) in gustatory nucleus solitary tract (rNST), whole cell patch-clamp recordings were made horizontal brain stem slices newborn rats. Neurons labeled with biocytin to confirm both their location and morphology. IPSPs IPSCs evoked by delivering single, paired-pulse, tetanic stimulus shocks (0.1-ms duration) via a bipolar stimulating electrode placed on rNST. Pure...