[Unique characteristics of "the second brain" - The enteric nervous system].

Enteric nervous system (ENS) is composed of intestinal submucosal and myenteric plexuses. ENS may independently regulate intestinal digestive and absorptive function, and it is also known as "the second brain" or gut brain. ENS has significant specificity relative to central nervous system (CNS) in properties and functional activities of neurons and neural circuits.

Docosahexaenoic Acid-Phosphatidylcholine Improves Cognitive Deficits in an Aβ23-35-Induced Alzheimer's Disease Rat Model.

Both Docosahexaenoic acid (DHA) and Phosphatidylcholine (PC) have been shown to halt the pathogenesis of Alzheimer disease (AD) and vascular dementia. This study aimed to investigate the role of DHA-containing PC (DHA-PC) in the improvement of Aβ25-35-induced cognitive deficits in rats. Aβ25-35-induced AD rats were treated for 30 days with DHA-PC, which was extracted from Sthenoteuthis oualaniensis spawns.

β-Nicotinamide adenine dinucleotide acts at prejunctional adenosine A1 receptors to suppress inhibitory musculomotor neurotransmission in guinea pig colon and human jejunum.

Intracellular microelectrodes were used to record neurogenic inhibitory junction potentials in the intestinal circular muscle coat. Electrical field stimulation was used to stimulate intramural neurons and evoke contraction of the smooth musculature. Exposure to β-nicotinamide adenine dinucleotide (β-NAD) did not alter smooth muscle membrane potential in guinea pig colon or human jejunum.

Neurochemical phenotype and function of endomorphin 2-immunopositive neurons in the myenteric plexus of the rat colon.

The distribution and activity of endomorphins (EMs), which are endogenous μ-opioid receptor (MOR) ligands in the gastrointestinal tract (GI), are yet to be elucidated. The current study aimed to shed light on this topic. EM2 was expressed in the enteric neurons in the myenteric plexus of the mid-colon.

Innervation of enteric mast cells by primary spinal afferents in guinea pig and human small intestine.

Mast cells express the substance P (SP) neurokinin 1 receptor and the calcitonin gene-related peptide (CGRP) receptor in guinea pig and human small intestine. Enzyme-linked immunoassay showed that activation of intramural afferents by antidromic electrical stimulation or by capsaicin released SP and CGRP from human and guinea pig intestinal segments. Electrical stimulation of the afferents evoked slow excitatory postsynaptic potentials (EPSPs) in the enteric nervous system.

Dietary glutamate: interactions with the enteric nervous system.

Background/aims: Digestion of dietary protein elevates intraluminal concentrations of glutamate in the small intestine, some of which gain access to the enteric nervous system (ENS). Glutamate, in the central nervous system (CNS), is an excitatory neurotransmitter. A dogma that glutamatergic neurophysiology in the ENS recapitulates CNS glutamatergic function persists.

Mast cell expression of the serotonin1A receptor in guinea pig and human intestine.

Serotonin [5-hydroxytryptamine (5-HT)] is released from enterochromaffin cells in the mucosa of the small intestine. We tested a hypothesis that elevation of 5-HT in the environment of enteric mast cells might degranulate the mast cells and release mediators that become paracrine signals to the enteric nervous system, spinal afferents, and secretory glands. Western blotting, immunofluorescence, ELISA, and pharmacological analysis were used to study expression of 5-HT receptors by mast cells in the small intestine and action of 5-HT to degranulate the mast cells and release histamine in guinea pig small intestine and segments of human jejunum discarded during Roux-en-Y gastric bypass surgeries.

Glucagon-like peptide-1 modulates neurally evoked mucosal chloride secretion in guinea pig small intestine in vitro.

Glucagon-like peptide-1 (GLP-1) acts at the G protein-coupled receptor, GLP-1R, to stimulate secretion of insulin and to inhibit secretion of glucagon and gastric acid. Involvement in mucosal secretory physiology has received negligible attention. We aimed to study involvement of GLP-1 in mucosal chloride secretion in the small intestine.

Lubiprostone reverses the inhibitory action of morphine on mucosal secretion in human small intestine.

Background And Aims: Treatments with morphine or opioid agonists cause constipation. Lubiprostone is approved for treatment of adult idiopathic constipation and constipation-predominant IBS in adult women. We tested whether lubiprostone can reverse morphine-suppression of mucosal secretion in human intestine and explored the mechanism of action.

Lubiprostone reverses the inhibitory action of morphine on intestinal secretion in guinea pig and mouse.

Lubiprostone activates ClC-2 chloride channels in epithelia. It is approved for treatment of chronic idiopathic constipation in adults and constipation-predominate irritable bowel syndrome in women. We tested a hypothesis that lubiprostone can reverse the constipating action of morphine and investigated the mechanism of action.

Stimulation of mucosal secretion by lubiprostone (SPI-0211) in guinea pig small intestine and colon.

Actions of lubiprostone, a selective type-2 chloride channel activator, on mucosal secretion were investigated in guinea pig small intestine and colon. Flat-sheet preparations were mounted in Ussing flux chambers for recording short-circuit current (Isc) as a marker for electrogenic chloride secretion. Lubiprostone, applied to the small intestinal mucosa in eight concentrations ranging from 1-3000 nM, evoked increases in Isc in a concentration-dependent manner with an EC50 of 42.

Differential expression of canonical (classical) transient receptor potential channels in guinea pig enteric nervous system.

The canonical transient receptor potential (TRPC) family of ion channels is implicated in many neuronal processes including calcium homeostasis, membrane excitability, synaptic transmission, and axon guidance. TRPC channels are postulated to be important in the functional neurobiology of the enteric nervous system (ENS); nevertheless, details for expression in the ENS are lacking. Reverse transcriptase-polymerase chain reaction, Western blotting, and immunohistochemistry were used to study the expression and localization of TRPC channels.

Inhibitory neuromuscular transmission mediated by the P2Y1 purinergic receptor in guinea pig small intestine.

ATP is a putative inhibitory neurotransmitter responsible for inhibitory junction potentials (IJPs) at neuromuscular junctions (IJPs) in the intestine. This study tested the hypothesis that the purinergic P2Y(1) receptor subtype mediates the IJPs. IJPs were evoked by focal electrical stimulation in the myenteric plexus and recorded with "sharp" intracellular microelectrodes in the circular muscle coat.

Forebrain NMDA receptors contribute to neuronal spike responses in adult mice.

Glutamate is the major fast excitatory transmitter in the central nervous system. While normal synaptic transmission is mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate receptors, N-methyl-D-aspartate (NMDA) receptors are thought to selectively contribute to plasticity. Genetically enhancing NMDA receptor functions enhances animal behavior in normal physiological learning and enhances their sensitivity in the case of tissue injury.

Platelet-activating factor in the enteric nervous system of the guinea pig small intestine.

Platelet-activating factor (PAF) is a proinflammatory mediator that may influence neuronal activity in the enteric nervous system (ENS). Electrophysiology, immunofluorescence, Western blot analysis, and RT-PCR were used to study the action of PAF and the expression of PAF receptor (PAFR) in the ENS. PAFR immunoreactivity (IR) was expressed by 6.

Forebrain overexpression of CaMKII abolishes cingulate long term depression and reduces mechanical allodynia and thermal hyperalgesia.

Activity-dependent synaptic plasticity is known to be important in learning and memory, persistent pain and drug addiction. Glutamate NMDA receptor activation stimulates several protein kinases, which then trigger biochemical cascades that lead to modifications in synaptic efficacy. Genetic and pharmacological techniques have been used to show a role for Ca2+/calmodulin-dependent kinase II (CaMKII) in synaptic plasticity and memory formation.

Neurogenic secretion mediated by the purinergic P2Y1 receptor in guinea-pig small intestine.

We tested the hypothesis that ATP is an enteric neurotransmitter that acts at P2Y1 excitatory purinergic receptors on intestinal secretomotor neurons to evoke neurogenic mucosal secretion in the guinea pig. Ussing chamber methods for studying neurogenic intestinal secretion were used to test the hypothesis. Application of ATP evoked concentration-dependent increases in short circuit current (Isc) indicative of stimulation of electrolyte secretion.

Distribution and chemical coding of corticotropin-releasing factor-immunoreactive neurons in the guinea pig enteric nervous system.

Immunofluorescence was used to study immunoreactivity (IR) for corticotropin-releasing factor (CRF) in the guinea pig enteric nervous system. CRF-IR was expressed in both the myenteric and the submucosal plexuses of all regions of the large and small intestine and the myenteric plexus of the stomach. CRF-IR nerve fibers were present in the myenteric and submucosal plexuses, in the circular muscle coat, and surrounding submucosal arterioles.

Angiotensin receptors and actions in guinea pig enteric nervous system.

Actions of ANG II on electrical and synaptic behavior of enteric neurons in the guinea pig small intestine were studied. Exposure to ANG II depolarized the membrane potential and elevated neuronal excitability. The number of responding neurons was small, with responses to ANG II in 32% of submucosal neurons and 25% of myenteric neurons.

Expression of type 1 corticotropin-releasing factor receptor in the guinea pig enteric nervous system.

Reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, electrophysiological recording, and intraneuronal injection of the neuronal tracer biocytin were integrated in a study of the functional expression of corticotropin-releasing factor (CRF) receptors in the guinea pig enteric nervous system. RT-PCR revealed expression of CRF1 receptor mRNA, but not CRF2, in both myenteric and submucosal plexuses. Immunoreactivity for the CRF1 receptor was distributed widely in the myenteric plexus of the stomach and small and large intestine and in the submucosal plexus of the small and large intestine.

NMDA receptors contribute to synaptic transmission in anterior cingulate cortex of adult mice.

Glutamatergic synapses are common excitatory chemical connections in mammalian central nervous system. At these synapses, most of baseline synaptic transmission is mediated by glutamate AMPA receptors. NMDA receptors that are sensitive to voltage-dependent magnesium blockade selectively contribute to activity-dependent synaptic plasticity.

Impaired NMDA receptor-mediated postsynaptic function and blunted NMDA receptor-dependent persistent pain in mice lacking postsynaptic density-93 protein.

Modification of synaptic NMDA receptor (NMDAR) expression influences NMDAR-mediated synaptic function and associated persistent pain. NMDARs directly bind to a family of membrane-associated guanylate kinases (MAGUKs) that regulate surface and synaptic NMDAR trafficking in the CNS. We report here that postsynaptic density-93 protein (PSD-93), a postsynaptic neuronal MAGUK, is expressed abundantly in spinal dorsal horn and forebrain, where it colocalizes and interacts with NMDAR subunits NR2A and NR2B.

Interleukin-2 regulates membrane potentials and calcium channels via mu opioid receptors in rat dorsal root ganglion neurons.

Our previous studies revealed that interleukin-2 (IL-2) exerted peripheral antinociception that was partially mediated by mu opioid receptors. No ionic explanations of this effect have yet been reported. The present study was designed to investigate effects of IL-2 on the physiological properties of capsaicin-sensitive small dorsal root ganglion (DRG) neurons, which are predominantly responsible for nociceptive transmission from the periphery to the spinal cord.

Synergistic enhancement of glutamate-mediated responses by serotonin and forskolin in adult mouse spinal dorsal horn neurons.

Glutamate is the major excitatory amino acid neurotransmitter in the CNS, including the neocortex, hippocampus, and spinal cord. Normal synaptic transmission is mainly mediated by glutamate AMPA and/or kainate receptors. Glutamate N-methyl-D-aspartate (NMDA) receptors are normally inactive and only activated when a sufficient postsynaptic depolarization is induced by the activity.