Excitatory effect of P2X receptor activation on mesenteric afferent nerves in the anaesthetised rat

Kirkup, Anthony J.; Booth, Charlotte E.; Chessell, Iain P.; Humphrey, P. P. A.; Grundy, David

doi:10.1111/j.1469-7793.1999.00551.x

Cited by 79 publications

(54 citation statements)

References 43 publications

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“…We did not examine whether this agonist can also sensitise C-MH fibres to heat although it was clear that C-MH fibres were activated more robustly by this agonist than heat-insensitive C-fibres (Figs 2 and 4). Other groups have examined the effects of P2X agonists on primary afferents innervating visceral and joint tissues (Dowd et al 1998;Kirkup et al 1999). The responses observed were sensitive to the non-specific P2X antagonist pyridoxal-phosphate-6-azophenyl-2Ÿ,4fi-disulphonic acid (PPADS).…”

Section: Discussionmentioning

confidence: 99%

Selective activation of nociceptors by P2X receptor agonists in normal and inflamed rat skin

Hamilton¹,

McMahon²,

Lewin³

2001

The Journal of Physiology

110

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ATP can elicit pain in humans and, together with other P2X channel agonists, can produce nocifensive responses in rodents. We used the rat in vitro skin‐nerve preparation to quantify primary afferent responses to ATP and its stable analogue α,β‐methylene ATP in normal and carrageenan‐inflamed skin. Both ATP and α,β‐methylene ATP were found to specifically activate the peripheral terminals of Aδ and C‐fibre nociceptors in the skin. Thirty‐nine per cent of the nociceptors tested responded to the maximal dose of α,β‐methylene ATP (5 mm). In contrast, non‐nociceptive, low‐threshold mechano‐sensitive fibres were never activated by the same agonist concentrations. Amongst the nociceptor population, C‐mechanoheat fibres (C‐MH or polymodal nociceptors) were markedly more responsive to P2X agonists than mechanonociceptors (C‐M nociceptors) with Aδ‐ or C‐fibre axons. Both C‐mechanoheat and C‐mechanonociceptors were activated by α,β‐methylene ATP doses as low as 50 μm. In skin inflamed with carrageenan 3‐4 h before recording both the number of responsive C‐fibre nociceptors and their response magnitude increased. The increased neural response under inflammatory conditions was largely observed in C‐mechanoheat or polymodal nociceptors. After low doses of P2X agonists C‐MH fibres but not C‐M fibres developed elevated ongoing activity and this effect was only seen after carrageenan inflammation. The time course of α,β‐methylene ATP‐evoked discharges in nociceptors was found to correlate well with the time course of behavioural nocifensive responses in rats to the same agonist described in a previous study (Hamilton et al. 1999). We conclude that the rapid increase in the number of α,β‐methylene ATP responsive nociceptors and the increased magnitude of the neural response following carrageenan inflammation explains why very low concentrations of such agonists can cause pain in inflammatory states.

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Section: Discussionmentioning

confidence: 99%

Selective activation of nociceptors by P2X receptor agonists in normal and inflamed rat skin

Hamilton¹,

McMahon²,

Lewin³

2001

The Journal of Physiology

110

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“…Well-known ligands for these receptors are ATP for P2Y1 and ATP and UTP for P2Y2 and P2Y4 (9). Previous studies have shown that ATP may be a neuromodulatory agent in sensory transduction, and possibly in nociception (6,13,20,28,45). In a previous study it was noted that cells referred to as subepithelial fibroblasts in small intestines of rat expressed P2Y1 receptors and released ATP in response to mechanical stimulation (16).…”

Section: Discussionmentioning

confidence: 99%

A novel population of subepithelial platelet-derived growth factor receptor α-positive cells in the mouse and human colon

Kurahashi

Nakano

Peri

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…It may be more important that increased intracellular Ca 2+ can stimulate exocytosis of signalling molecules. Hepatocytes are known to utilise ATP as an autocrine-paracrine signalling molecule (72,73) and some afferent nerves are activated by ATP (74) . Depolarisation of a hepatocyte could trigger release of intracellular Ca 2+ stores (75) , leading to exocytosis of ATP, which could then move through the extracellular space to nearby parasympathetic nerves, binding purinergic receptors and leading to the generation of action potentials.…”

Section: Weaknesses In the Modelmentioning

confidence: 99%

Control of food intake by metabolism of fuels: a comparison across species

Allen

Bradford

2012

Proc. Nutr. Soc.

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Research with laboratory species suggests that meals can be terminated by peripheral signals carried to brain feeding centres via hepatic vagal afferents, and that these signals are affected by oxidation of fuels. Pre-gastric fermentation in ruminants greatly alters fuels, allowing mechanisms conserved across species to be studied with different types and temporal absorption of fuels. These fuels include SCFA, glucose, lactate, amino acids and long-chain fatty acid (FA) isomers, all of which are absorbed and metabolised by different tissues at different rates. Propionate is produced by rumen microbes, absorbed within the timeframe of meals, and quickly cleared by the liver. Its hypophagic effects are variable, likely due to its fate; propionate is utilised for gluconeogenesis or oxidised and also stimulates oxidation of acetyl-CoA by anapleurosis. In contrast, acetate has little effect on food intake, likely because its uptake by the ruminant liver is negligible. Glucose is hypophagic in non-ruminants but not ruminants and unlike non-ruminant species, uptake of glucose by ruminant liver is negligible, consistent with the differences in hypophagic effects between them. Inhibition of FA oxidation increases food intake, whereas promotion of FA oxidation suppresses food intake. Hypophagic effects of fuel oxidation also vary with changes in metabolic state. The objective of this paper is to compare the type and utilisation of fuels and their effects on feeding across species. We believe that the hepatic oxidation theory allows insight into mechanisms controlling feeding behaviour that can be used to formulate diets to optimise energy balance in multiple species. Comparative metabolism: Food intake: Hepatic oxidationComparative metabolism can provide a valuable tool to improve understanding of physiological control mechanisms by investigating the similarities and differences across species. This paper addresses comparative aspects of the control of feeding behaviour by peripheral signals generated by oxidation of fuels. Research with rodents and other laboratory species indicates that inhibition of fuel oxidation stimulates feeding, whereas stimulation of oxidation inhibits feeding, and that the signal to brain feeding centres is via hepatic vagal afferents (1) . Feeding behaviour of rats has been related to energy charge in the liver and synergistic effects of metabolic inhibitors suggest an integrated mechanism with a common signal related to hepatic energy status from oxidation of various fuels (2) . However, the liver is only sparsely innervated with afferent fibres and the common hepatic vagus also innervates other tissues, including the duodenum (3) . The enterocyte was recently proposed as the primary sensor for fuel oxidation, casting doubt on a signal from the liver (4) . Evaluation of the ruminant model and comparison with non-ruminant models provides important insight into this issue because pre-gastric fermentation in ruminants greatly alters the type and temporal pattern of absorption of fuels. Rumen micr...

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Excitatory effect of P2X receptor activation on mesenteric afferent nerves in the anaesthetised rat

Cited by 79 publications

References 43 publications

Selective activation of nociceptors by P2X receptor agonists in normal and inflamed rat skin

Selective activation of nociceptors by P2X receptor agonists in normal and inflamed rat skin

A novel population of subepithelial platelet-derived growth factor receptor α-positive cells in the mouse and human colon

Control of food intake by metabolism of fuels: a comparison across species

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