Evidence for the involvement of ATP, but not of VIP/PACAP or nitric oxide, in the excitatory effect of capsaicin in the small intestine

L. Barthó, Zsófia Lázár, L. Lénárd, R. Benkó, G. Tóth, B. Penke, J. Szolcsányi, Carlo Alberto Maggi

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Abstract

The contractile effect of capsaicin in the guinea-pig small intestine involves an activation of enteric cholinergic neurons. Our present data show that the P2 purinoceptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 30 μM) significantly reduces the contractile response to capsaicin (2 μM) in the presence, but not in the absence, of the tachykinin receptor antagonists [O-Pro9, (Spiro-γ-lactam)Leu10, Trp11]physalaemin (1-11) (GR 82334; 3 μM) and (S)-(N)-(1-(3-(1-benzoyl-3-(3,4-dichlorophenyl)piperidin-3-yl)propyl)-4-phenylpiperidine-4-yl)-N-methylacetamide (SR 142801; 100 nM) (for blocking tachykinin NK1 and NK3 receptors, respectively). PPADS (30 μM) fails to influence submaximal cholinergic contractions evoked by cholecystokinin octapeptide (CCK-8; 2-3 nM) or senktide (1 nM), or the direct smooth muscle-contracting effect of histamine (100-200 nM). A higher concentration (300 μM) of PPADS is also without effect against the stimulatory action of cholecystokinin octapeptide. This means that PPADS can probably be safely used as a purinoceptor antagonist in intestinal preparations. The putative pituitary adenylate cyclase activating peptide (PACAP) receptor antagonist PACAP-(6-38) (3 μM) significantly reduces the contractile effect of PACAP-(1-38) (10 nM) and abolishes that of vasoactive intestinal polypeptide (VIP; 10 nM). PACAP-(6-38) (3 μM) fails to influence the effect of capsaicin (2 μM) both in the absence and in the presence of tachykinin receptor antagonists. The nitric oxide (NO) synthase inhibitor N(G)-nitro-L-arginine (L-NOARG; 100 μM) also fails to inhibit the capsaicin-induced motor response. We conclude that an endogenous ligand of PPADS-sensitive P2 purinoceptors (possibly ATP), but not a VIP/PACAP-like peptide or NO, is involved in the nontachykininergic activation of cholinergic neurons in the course of the capsaicin-induced contraction. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)183-188
Number of pages6
JournalEuropean Journal of Pharmacology
Volume392
Issue number3
DOIs
Publication statusPublished - Mar 31 2000

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Capsaicin
Adenylyl Cyclases
Small Intestine
Nitric Oxide
Adenosine Triphosphate
Sincalide
Peptides
Tachykinin Receptors
Cholinergic Neurons
Purinergic P2 Receptor Antagonists
Physalaemin
Purinergic Antagonists
Pituitary Adenylate Cyclase-Activating Polypeptide Receptors
Purinergic P2 Receptors
Tachykinins
Lactams
Nitroarginine
Vasoactive Intestinal Peptide
Nitric Oxide Synthase
Cholinergic Agents

Keywords

  • Capsaicin
  • Myenteric neuron
  • NO (Nitric oxide)
  • PACAP (Pituitary adenylate cyclase activating peptide)
  • PPADS (Pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid)
  • Small intestine
  • VIP (Vasoactive intestinal polypeptide)

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

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title = "Evidence for the involvement of ATP, but not of VIP/PACAP or nitric oxide, in the excitatory effect of capsaicin in the small intestine",
abstract = "The contractile effect of capsaicin in the guinea-pig small intestine involves an activation of enteric cholinergic neurons. Our present data show that the P2 purinoceptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 30 μM) significantly reduces the contractile response to capsaicin (2 μM) in the presence, but not in the absence, of the tachykinin receptor antagonists [O-Pro9, (Spiro-γ-lactam)Leu10, Trp11]physalaemin (1-11) (GR 82334; 3 μM) and (S)-(N)-(1-(3-(1-benzoyl-3-(3,4-dichlorophenyl)piperidin-3-yl)propyl)-4-phenylpiperidine-4-yl)-N-methylacetamide (SR 142801; 100 nM) (for blocking tachykinin NK1 and NK3 receptors, respectively). PPADS (30 μM) fails to influence submaximal cholinergic contractions evoked by cholecystokinin octapeptide (CCK-8; 2-3 nM) or senktide (1 nM), or the direct smooth muscle-contracting effect of histamine (100-200 nM). A higher concentration (300 μM) of PPADS is also without effect against the stimulatory action of cholecystokinin octapeptide. This means that PPADS can probably be safely used as a purinoceptor antagonist in intestinal preparations. The putative pituitary adenylate cyclase activating peptide (PACAP) receptor antagonist PACAP-(6-38) (3 μM) significantly reduces the contractile effect of PACAP-(1-38) (10 nM) and abolishes that of vasoactive intestinal polypeptide (VIP; 10 nM). PACAP-(6-38) (3 μM) fails to influence the effect of capsaicin (2 μM) both in the absence and in the presence of tachykinin receptor antagonists. The nitric oxide (NO) synthase inhibitor N(G)-nitro-L-arginine (L-NOARG; 100 μM) also fails to inhibit the capsaicin-induced motor response. We conclude that an endogenous ligand of PPADS-sensitive P2 purinoceptors (possibly ATP), but not a VIP/PACAP-like peptide or NO, is involved in the nontachykininergic activation of cholinergic neurons in the course of the capsaicin-induced contraction. Copyright (C) 2000 Elsevier Science B.V.",
keywords = "Capsaicin, Myenteric neuron, NO (Nitric oxide), PACAP (Pituitary adenylate cyclase activating peptide), PPADS (Pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid), Small intestine, VIP (Vasoactive intestinal polypeptide)",
author = "L. Barth{\'o} and Zs{\'o}fia L{\'a}z{\'a}r and L. L{\'e}n{\'a}rd and R. Benk{\'o} and G. T{\'o}th and B. Penke and J. Szolcs{\'a}nyi and Maggi, {Carlo Alberto}",
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TY - JOUR

T1 - Evidence for the involvement of ATP, but not of VIP/PACAP or nitric oxide, in the excitatory effect of capsaicin in the small intestine

AU - Barthó, L.

AU - Lázár, Zsófia

AU - Lénárd, L.

AU - Benkó, R.

AU - Tóth, G.

AU - Penke, B.

AU - Szolcsányi, J.

AU - Maggi, Carlo Alberto

PY - 2000/3/31

Y1 - 2000/3/31

N2 - The contractile effect of capsaicin in the guinea-pig small intestine involves an activation of enteric cholinergic neurons. Our present data show that the P2 purinoceptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 30 μM) significantly reduces the contractile response to capsaicin (2 μM) in the presence, but not in the absence, of the tachykinin receptor antagonists [O-Pro9, (Spiro-γ-lactam)Leu10, Trp11]physalaemin (1-11) (GR 82334; 3 μM) and (S)-(N)-(1-(3-(1-benzoyl-3-(3,4-dichlorophenyl)piperidin-3-yl)propyl)-4-phenylpiperidine-4-yl)-N-methylacetamide (SR 142801; 100 nM) (for blocking tachykinin NK1 and NK3 receptors, respectively). PPADS (30 μM) fails to influence submaximal cholinergic contractions evoked by cholecystokinin octapeptide (CCK-8; 2-3 nM) or senktide (1 nM), or the direct smooth muscle-contracting effect of histamine (100-200 nM). A higher concentration (300 μM) of PPADS is also without effect against the stimulatory action of cholecystokinin octapeptide. This means that PPADS can probably be safely used as a purinoceptor antagonist in intestinal preparations. The putative pituitary adenylate cyclase activating peptide (PACAP) receptor antagonist PACAP-(6-38) (3 μM) significantly reduces the contractile effect of PACAP-(1-38) (10 nM) and abolishes that of vasoactive intestinal polypeptide (VIP; 10 nM). PACAP-(6-38) (3 μM) fails to influence the effect of capsaicin (2 μM) both in the absence and in the presence of tachykinin receptor antagonists. The nitric oxide (NO) synthase inhibitor N(G)-nitro-L-arginine (L-NOARG; 100 μM) also fails to inhibit the capsaicin-induced motor response. We conclude that an endogenous ligand of PPADS-sensitive P2 purinoceptors (possibly ATP), but not a VIP/PACAP-like peptide or NO, is involved in the nontachykininergic activation of cholinergic neurons in the course of the capsaicin-induced contraction. Copyright (C) 2000 Elsevier Science B.V.

AB - The contractile effect of capsaicin in the guinea-pig small intestine involves an activation of enteric cholinergic neurons. Our present data show that the P2 purinoceptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 30 μM) significantly reduces the contractile response to capsaicin (2 μM) in the presence, but not in the absence, of the tachykinin receptor antagonists [O-Pro9, (Spiro-γ-lactam)Leu10, Trp11]physalaemin (1-11) (GR 82334; 3 μM) and (S)-(N)-(1-(3-(1-benzoyl-3-(3,4-dichlorophenyl)piperidin-3-yl)propyl)-4-phenylpiperidine-4-yl)-N-methylacetamide (SR 142801; 100 nM) (for blocking tachykinin NK1 and NK3 receptors, respectively). PPADS (30 μM) fails to influence submaximal cholinergic contractions evoked by cholecystokinin octapeptide (CCK-8; 2-3 nM) or senktide (1 nM), or the direct smooth muscle-contracting effect of histamine (100-200 nM). A higher concentration (300 μM) of PPADS is also without effect against the stimulatory action of cholecystokinin octapeptide. This means that PPADS can probably be safely used as a purinoceptor antagonist in intestinal preparations. The putative pituitary adenylate cyclase activating peptide (PACAP) receptor antagonist PACAP-(6-38) (3 μM) significantly reduces the contractile effect of PACAP-(1-38) (10 nM) and abolishes that of vasoactive intestinal polypeptide (VIP; 10 nM). PACAP-(6-38) (3 μM) fails to influence the effect of capsaicin (2 μM) both in the absence and in the presence of tachykinin receptor antagonists. The nitric oxide (NO) synthase inhibitor N(G)-nitro-L-arginine (L-NOARG; 100 μM) also fails to inhibit the capsaicin-induced motor response. We conclude that an endogenous ligand of PPADS-sensitive P2 purinoceptors (possibly ATP), but not a VIP/PACAP-like peptide or NO, is involved in the nontachykininergic activation of cholinergic neurons in the course of the capsaicin-induced contraction. Copyright (C) 2000 Elsevier Science B.V.

KW - Capsaicin

KW - Myenteric neuron

KW - NO (Nitric oxide)

KW - PACAP (Pituitary adenylate cyclase activating peptide)

KW - PPADS (Pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid)

KW - Small intestine

KW - VIP (Vasoactive intestinal polypeptide)

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U2 - 10.1016/S0014-2999(00)00137-0

DO - 10.1016/S0014-2999(00)00137-0

M3 - Article

VL - 392

SP - 183

EP - 188

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

IS - 3

ER -