Effects of Acute Administration of and Tachyphylaxis to α,β‐Methylene ATP in the Guinea‐Pig Small Intestine

Benkó, Rita; Undi, Sarolta; Wolf, Matyas; Barthó, L.

doi:10.1111/j.1742-7843.2005.pto_117.x

Cited by 16 publications

(21 citation statements)

References 17 publications

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“…Whereas with a dose of 1 μmol/l of αβ-methylene ATP, we did not find a significant alteration of the nicotine effects, an observation that had also been reported by Benkó et al [9] with even much high doses of this compound, we found that the P2X antagonist PPADS reduced the nicotine contraction and prevented the nicotine desensitization. On the other hand, it has been shown that hexamethonium has no effect on the αβ-methylene ATP contraction [9] .…”

Section: Discussionsupporting

confidence: 66%

“…It has also already been reported by Benkó et al [9] that αβ-methylene ATP can reduce the cholinergic twitch to some extent, and this effect had been ascribed to some type of 'tachyphylaxis' on the motor neuron. The P2X ligand-gated ion channel allows the inflow of sodium and calcium ion, leading to depolarization and activation of calcium-sensitive intracellular processes [4] .…”

Section: Discussionmentioning

confidence: 75%

“…On the other hand, it has been shown that hexamethonium has no effect on the αβ-methylene ATP contraction [9] . Certainly, we can deduce from the present and from previous experiments that there exists an interaction between nicotinic and P2 purinergic receptors in myenteric neurons in the ileum of guinea pig.…”

Section: Discussionmentioning

confidence: 99%

“…We have provided evidence for an opioidergic and glutamatergic modulation of the electrical twitch response in the ileum of guinea pig [6,7] . Previous investigations have provided evidence that P2X purinoceptors are involved in the prejunctional modulation of cholinergic neurotransmission between the myenteric plexus and longitudinal smooth muscle in the small intestine of guinea pig [8,9] . Electrophysiological work has found evidence for a functional cross-inhibition between nicotinic acetylcholine receptors (nAChRs) and P2X receptors in myenteric neurons in the ileum of guinea pig [10,11] .…”

Section: Introductionmentioning

confidence: 99%

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Nicotine-Induced Modulation of the Cholinergic Twitch Response in the Ileum of Guinea Pig

Donnerer

Liebmann²

2015

Pharmacology

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In the present study, the direct drug effects of nicotine and its effects on the cholinergic twitch responses of the electrically stimulated longitudinal muscle-myenteric plexus strip from the ileum of guinea pig were investigated. Nicotine dose-dependently (0.3-10 µmol/l) evoked the well-known contractile responses on its own. Whereas the interposed twitch responses remained present without a change in height at 1 µmol/l nicotine, a nicotine concentration of 3 µmol/l slightly and a concentration of 10 µmol/l markedly diminished the twitch during their presence. After the washout of 1-10 µmol/l nicotine, the height of the twitch response was also temporarily and significantly reduced by 30-77%. The P2X purinoceptor agonist αβ-methylene ATP (1-10 µmol/l) dose-dependently induced contractions on its own and reduced the twitch response during its presence in the organ bath; however, it did not diminish the twitch responses after washout of the drug as nicotine did. The P2X antagonist pyridoxalphosphate-6-azophenyl-2'-4'-disulphonic acid, the NMDA channel blocker MK-801 and the inhibitor of small conductance Ca(2+)-activated K(+) (SK) channels apamin reduced the contractile effect of 1 µmol/l nicotine. Apamin also significantly prevented the 'post-nicotine inhibition of the twitch' following the washout of 1-3 µmol/l nicotine. As a conclusion, we provide evidence for a functional interaction between nicotinic receptors and the P2X receptors in the ileum of the guinea pig. The 'post-nicotine inhibition of the twitch' is not due to nicotinic acetylcholine receptor desensitization or transmitter depletion, but most probably the secondary effects of nicotine on SK channels determine the reduced cholinergic motor neuron excitability.

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Section: Discussionsupporting

confidence: 66%

Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Nicotine-Induced Modulation of the Cholinergic Twitch Response in the Ileum of Guinea Pig

Donnerer

Liebmann²

2015

Pharmacology

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“…At least in the mouse ileum, smooth muscle cells were strongly immunoreactive for P2Y 1 receptors [7] , and myenteric plexus neurons in the guinea-pig ileum were shown to express the P2Y 6 and P2Y 12 receptor [36] . However, interspecies differences are very likely, because α,β-Me-ATP-induced contractions of guinea-pig ileum were sensitive to the P2X 1 receptor antagonist NF279 and the P2X receptor-preferring blocker PPADS [37] . This finding is in contrast to the present results using rat ileum, which point to a predominant P2Y receptormediated contraction following exposure to α,β-Me-ATP.…”

Section: Wwwchinapharcom Mader F Et Almentioning

confidence: 99%

P2Y receptor-mediated transient relaxation of rat longitudinal ileum preparations involves phospholipase C activation, intracellular Ca2+ release and SK channel activation

et al. 2016

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Aim: Purinergic signaling plays a major role in the enteric nervous system, where it governs gut motility through a number of P2X and P2Y receptors. The aim of this study was to investigate the P2Y receptor-mediated motility in rat longitudinal ileum preparations. Methods: Ileum smooth muscle strips were prepared from rats, and fixed in an organ bath. Isometric contraction and relaxation responses of the muscle strips were measured with force transducers. Drugs were applied by adding of stock solutions to the organ bath to yield the individual final concentrations. Results: Application of the non-hydrolyzable P2 receptor agonists α,β-Me-ATP or 2-Me-S-ADP (10, 100 µmol/L) dose-dependently elicited a transient relaxation response followed by a sustained contraction. The relaxation response was largely blocked by SK channel blockers apamin (500 nmol/L) and UCL1684 (10 µmol/L), PLC inhibitor U73122 (100 µmol/L), IP 3 receptor blocker 2-APB (100 µmol/L) or sarcoendoplasmic Ca 2+ ATPase inhibitor thapsigargin (1 µmol/L), but not affected by atropine, NO synthase blocker L-NAME or tetrodotoxin. Furthermore, α,β-Me-ATP-induced relaxation was suppressed by P2Y 1 receptor antagonist MRS2179 (50 µmol/L) or P2Y 13 receptor antagonist MRS2211 (100 µmol/L), and was abolished by co-application of the two antagonists, whereas 2-Me-S-ADP-induced relaxation was abolished by P2Y 6 receptor antagonist MRS2578 (50 µmol/L). In addition, P2Y 1 receptor antagonist MRS2500 (1 µmol/L) not only abolished α,β-Me-ATP-induced relaxation, but also suppressed 2-Me-S-ADP-induced relaxation. Conclusion: P2Y receptor agonist-induced transient relaxation of rat ileum smooth muscle strips is mediated predominantly by P2Y 1 receptor, but also by P2Y 6 and P2Y 13 receptors, and involves PLC, IP 3 , Ca 2+ release and SK channel activation, but is independent of acetylcholine and NO release.

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P2X receptors in the gut

Burnstock

2011

WIREs Membr Transp Signal

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Purinergic transmission, which uses ATP and its derivatives as extracellular signaling molecules, is widely distributed throughout all tissues and systems, including the gastrointestinal system. Ionotropic P2X purinoceptors have been identified in various parts of the enteric nervous system, including myenteric, submucosal motor, sensory, and secretomotor neurones, in enteric glial cells and interstitial cells of Cajal. Purinergic mechanosensory transduction, where there is release of ATP from mucosal epithelial cells during distension, stimulating subepithelial nerve endings of intrinsic and extrinsic sensory nerves to modulate peristalsis and initiate nociception. Purinergic signaling in the gut is involved in development, aging, and regeneration of the gut, and the pathophysiology of enteric purinergic signaling in diseases including irritable bowel syndrome, postoperative ileus, esophageal reflux, constipation, diarrhea, diabetes, Chaga's and Hirschprung's diseases.Myenteric neurons have been classified into two groups: Dogiel Type I/S neurons (which are motor neurons or interneurons) and Dogiel Type II/AH neurons (which are sensory neurons). ATP-induced hyperpolarizations reduced excitability of AH neurons, while ATP-induced depolarization increased excitability of most S neurons. 9 Later it was shown that ATP mediates fast synaptic potentials in enteric neurons. 22 P2X receptors mediated fast excitatory postsynaptic currents in guinea pig cultured myenteric neurons; these neurons express both fast-desensitizing α,β-methylene ATP (α,β-meATP)-sensitive P2X 1 -like receptors and slow-desensitizing α,β-meATP-insensitive P2X 2 -like receptors. 23 P2X 2 receptors were considered to be the dominant P2X receptor in cultured rat myenteric neurons. 24 In another study of guinea pig myenteric neurons, it was concluded that the P2X receptors on the neurons shared properties with P2X 4 and P2X 6 receptors. 25 ATP elevates [Ca 2+ ] i via P2 receptors in cultured Type II/AH neurons from adult guinea pigs' small intestine. 26 Fast excitatory postsynaptic potentials (EPSPs) mediated, at least in apart, via P2X receptors, are predominant in myenteric neurons along the small and large intestines of guinea pigs, but are rare in the gastric corpus. 27 Volume 1,

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Effects of Acute Administration of and Tachyphylaxis to α,β‐Methylene ATP in the Guinea‐Pig Small Intestine

Cited by 16 publications

References 17 publications

Nicotine-Induced Modulation of the Cholinergic Twitch Response in the Ileum of Guinea Pig

Nicotine-Induced Modulation of the Cholinergic Twitch Response in the Ileum of Guinea Pig

P2Y receptor-mediated transient relaxation of rat longitudinal ileum preparations involves phospholipase C activation, intracellular Ca2+ release and SK channel activation

P2X receptors in the gut

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