Potentiation of mouse vagal afferent mechanosensitivity by ionotropic and metabotropic glutamate receptors

Slattery, James A.; Page, Amanda J.; Dorian, Camilla; Brierley, Stuart M.; Blackshaw, L. Ashley

doi:10.1113/jphysiol.2006.117762

Cited by 42 publications

(31 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As mentioned above, virtually all vagal afferent neurons, including those that innervate the upper GI tract, express NMDA receptor subunit immunoreactivity (12,13). Furthermore, electrical activity recorded from the distal ends of cut vagal afferents is modulated by NMDA receptors (42), suggesting that receptors in peripheral vagal afferent membranes may participate in relaying sensory information to the brain. Immunoreactivity for glutamate and vesicular glutamate transporter (VGLUT) has been reported in neurons of enteric plexus of the guinea pig and rat small intestines (45,51).…”

Section: Discussionmentioning

confidence: 92%

“…This issue is not trivial because NMDA receptors are expressed by vagal afferent neurons in the nodose ganglia (12,13), as well as by central vagal afferent terminals and postsynaptic neurons in the NTS (1). Moreover, electrophysiological experiments suggest that peripheral NMDA receptors may modulate gastrointestinal vagal afferent activity (42). Therefore, it is plausible that NMDA receptor antagonists could alter the behavioral responses to CCK through actions at peripheral vagal afferent sites.…”

Section: Discussionmentioning

confidence: 99%

“…However, functional evidence suggests that NMDA receptors on peripheral vagal afferent fibers modulate gastrointestinal sensory information (42). Consequently, it is not clear whether systemically administered NMDA receptor antagonists attenuate reduction of food intake by interfering with CCK-induced vagal activation in the periphery, or by altering vagal communication in the hindbrain.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Reduction of food intake by cholecystokinin requires activation of hindbrain NMDA-type glutamate receptors

Wright

Campos

Herzog

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

injection of CCK reduces food intake and triggers a behavioral pattern similar to natural satiation. Reduction of food intake by CCK is mediated by vagal afferents that innervate the stomach and small intestine. These afferents synapse in the hindbrain nucleus of the solitary tract (NTS) where gastrointestinal satiation signals are processed. Previously, we demonstrated that intraperitoneal (IP) administration of either competitive or noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists attenuates reduction of food intake by CCK. However, because vagal afferents themselves express NMDA receptors at both central and peripheral endings, our results did not speak to the question of whether NMDA receptors in the brain play an essential role in reduction of feeding by CCK. We hypothesized that activation of NMDA receptors in the NTS is necessary for reduction of food intake by CCK. To test this hypothesis, we measured food intake following IP CCK, subsequent to NMDA receptor antagonist injections into the fourth ventricle, directly into the NTS or subcutaneously. We found that either fourth-ventricle or NTS injection of the noncompetitive NMDA receptor antagonist MK-801 was sufficient to inhibit CCK-induced reduction of feeding, while the same antagonist doses injected subcutaneously did not. Similarly fourth ventricle injection of D-3-(2-carboxypiperazin-4-yl)-1-propenyl-1-phosphoric acid (D-CPPene), a competitive NMDA receptor antagonist, also blocked reduction of food intake following IP CCK. Finally, DCPPene injected into the fourth ventricle attenuated CCK-induced expression of nuclear c-Fos immunoreactivity in the dorsal vagal complex. We conclude that activation of NMDA receptors in the hindbrain is necessary for the reduction of food intake by CCK. Hindbrain NMDA receptors could comprise a critical avenue for control and modulation of satiation signals to influence food intake and energy balance.vagus; satiation; gut-brain peptides SATIATION IS THE PROCESS by which food entering the gastrointestinal tract gradually reduces food intake, eventually resulting in termination of a meal. Previous reports from our group and others indicate that systemic administration of antagonists of N-methyl-D-aspartate-type glutamate receptors (NMDAr antagonists) delays satiation and increases meal size (see, for example, Refs. 8, 9, and 25). Additionally, we demonstrated that injecting NMDAr antagonists directly into the nucleus of the solitary tract (NTS), where vagal afferents from the gastrointestinal tract synapse, increases meal size (19,23,46) and that lesions of the NTS abolish this effect (47). These observations suggest that NMDA receptors, perhaps in the NTS, participate in vagally mediated control of food intake.The hypothesis that NMDA receptors participate in the process of satiation is supported by our prior reports that peripherally administered NMDA receptor antagonists attenuate reduction of food intake induced by CCK (11, 19), a gut peptide known to reduce food intake by activating abdominal vagal a...

show abstract

Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Reduction of food intake by cholecystokinin requires activation of hindbrain NMDA-type glutamate receptors

Wright

Campos

Herzog

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

show abstract

“…IGLEs are potently excited by ATP, 26,33 probably when this biochemical is released from damaged cells 34 ATP might also couple mechanosensitive epi-thelia to excitation of mechanoreceptors; 35,36 however, the time course of ATP release and its effects preclude a role in mechanotransduction by IGLEs. 26 The same endings in ferret stomach and oesophagus express inhibitory GABA B receptors, 37 excitatory and inhibitory metabotropic glutamate receptors 38,39 and are inhibited by ghrelin. Responses of IGLEs to ghrelin show marked plasticity, being upregulated after overfeeding.…”

Section: Vagal Intraganglionic Laminar Mechanoreceptorsmentioning

confidence: 99%

Extrinsic primary afferent signalling in the gut

Brookes

Spencer

Costa

et al. 2013

Nat Rev Gastroenterol Hepatol

246

216

View full text Add to dashboard Cite

Visceral sensory neurons activate reflex pathways that control gut function and also give rise to important sensations, such as fullness, bloating, nausea, discomfort, urgency and pain. Sensory neurons are organised into three distinct anatomical pathways to the central nervous system (vagal, thoracolumbar and lumbosacral). Although remarkable progress has been made in characterizing the roles of many ion channels, receptors, and second messengers in visceral sensory neurons, the basic aim of understanding how many classes there are, and how they differ, has proven difficult to achieve. We suggest that there are just five structurally distinct types of sensory endings in the gut wall that account for essentially all of the primary afferent neurons in the three pathways. Each of these five major structural types of endings seems to show distinctive combinations of physiological responses. These types are: 'intraganglionic laminar' endings in myenteric ganglia; 'mucosal' endings located in the subepithelial layer; 'muscular mucosal' afferents, with mechanosensitive endings close to the muscularis mucosae; 'intramuscular' endings, with endings within the smooth muscle layers; and 'vascular' afferents, with sensitive endings primarily on blood vessels. 'Silent' afferents might be a subset of inexcitable 'vascular' afferents, which can be switched on by inflammatory mediators.Extrinsic sensory neurons comprise an attractive focus for targeted therapeutic intervention in a range of gastrointestinal disorders.2

show abstract

“…In vertebrates, group I mGluRs are excitatory, causing slow depolarization through the activation of phospholipase C. G q proteins activate phospholipase C, which then activates diacylglycerol and inositol triphosphate as second messengers to open ion channels. G q proteins may also open ion channels directly without acting through second messengers (Meldrum, 2000;Sharon et al, 1997;Slattery et al, 2006). Perhaps robust excitation of B27 within the feeding CPG occurs as a result of both excitatory iGluRs resembling KA receptors and excitatory mGluRs resembling vertebrate group I mGluRs.…”

Section: Inhibitory Glutamate Receptors On B5 B19 and B27 Neuronsmentioning

confidence: 99%

Pharmacology of ionotropic and metabotropic glutamate receptors on neurons involved in feeding behavior in the pond snail, Helisoma trivolvis

Scannell

Dell'Ova

Quinlan

et al. 2008

Journal of Experimental Biology

View full text Add to dashboard Cite

SUMMARYGlutamate is a key regulatory neurotransmitter in the triphasic central pattern generator controlling feeding behavior in the pond snail, Helisoma trivolvis. It excites phase two motor neurons while inhibiting those in phases one and three. However, the receptors that mediate this regulation are only partially characterized. The purpose of these experiments was to further characterize the glutamate receptors on three buccal neurons modulated by glutamate. Intracellular recordings from B5, B19 and B27 neurons were taken during the perfusion of isolated buccal ganglia with agonists that are selective for different vertebrate glutamate receptors. The firing rate of all three neurons was inhibited in a dose-dependent manner by glutamate, including that of B27, a phase 2 motor neuron known to be excited by glutamate in vivo. Quisqualate also reduced the firing rate in all three neurons, and (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD), a relatively non-selective metabotropic glutamate receptor (mGluR) agonist, reduced the firing rate in B5 neurons, but not in B19 or B27 neurons. Agonists selective for vertebrate group I, II and III mGluRs did not affect the firing rate in any of the Helisoma buccal neurons tested, suggesting that mGluR agonist binding sites on these neurons do not closely resemble those on any vertebrate mGluR subtypes. An increase in frequency of action potentials was observed in all three cell types in the presence of 100·mol·l -1 kainate (KA), suggesting the presence of excitatory (S)-␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/KA-like receptors. However, electrotonic coupling between B19 and B27 neurons, and a lack of effect of KA on isolated B19 neurons suggest the excitatory effects of KA on this neuron are indirect. These findings suggest the presence of multiple glutamate receptor subtypes in molluscan neurons that do not always resemble vertebrate receptors pharmacologically.

show abstract

Potentiation of mouse vagal afferent mechanosensitivity by ionotropic and metabotropic glutamate receptors

Cited by 42 publications

References 56 publications

Reduction of food intake by cholecystokinin requires activation of hindbrain NMDA-type glutamate receptors

Reduction of food intake by cholecystokinin requires activation of hindbrain NMDA-type glutamate receptors

Extrinsic primary afferent signalling in the gut

Pharmacology of ionotropic and metabotropic glutamate receptors on neurons involved in feeding behavior in the pond snail, Helisoma trivolvis

Contact Info

Product

Resources

About