Inhibition of the NANC relaxation of the guinea-pig proximal colon longitudinal muscle by the purinoceptor antagonist PPADS, inhibition of nitric oxide synthase, but not by a PACAP/VIP antagonist

Barnabás Rózsai, Zsófia Lázár, R. Benkó, L. Barthó

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The effects of the P2-purinoceptor antagonist pyridoxal-phosphate-6-azophenyl-2′,4′-disulphonic acid (PPADS), the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine (L-NOARG), the K+channel blocker apamin, the pituitary adenylate cyclase activating peptide (PACAP) antagonist PACAP(6-38) and the sensory neuron-blocking drug capsaicin were examined on the non-adrenergic, non-cholinergic (NANC) relaxation evoked by electrical field stimulation in the longitudinal muscle of the guinea-pig proximal colon. Both PPADS (50 μM) and L-NOARG (100 μM) significantly inhibited the NANC relaxation. In the presence of L-NOARG, PPADS inhibited and apamin (100 nM) practically abolished the response. Capsaicin slightly but significantly enhanced the NANC relaxation at 10, but not at 1 Hz stimulation frequency. PACAP(6-38) (3 μM) had no effect on the NANC relaxation, although it abolished the relaxant effect of exogenous PACAP(1-27) (10 nM) and reduced that of exogenous vasoactive intestinal polypeptide (VIP, 30-100 nM) by about 60%. PPADS (50 μM) inhibited the relaxant action of exogenous adenosine 5′-triphosphate (ATP; 1 and 10 μM), the inhibition being stronger at 1 μM ATP. These data indicate that an exogenous P2-purinoceptor stimulant (possibly ATP) and NO are involved in the NANC relaxation of the guinea-pig colon. The 'non-nitrergic' apamin-sensitive component of the response might also include an unidentified transmitter. No evidence has been found for a mediating role of PACAP/VIP-like peptides.

Original languageEnglish
Pages (from-to)83-87
Number of pages5
JournalPharmacological Research
Volume43
Issue number1
DOIs
Publication statusPublished - 2001

Fingerprint

Purinergic Antagonists
Pyridoxal Phosphate
Nitroarginine
Apamin
Adenylyl Cyclases
Nitric Oxide Synthase
Guinea Pigs
Colon
Adenosine Triphosphate
Muscles
Peptides
Acids
Capsaicin
Purinergic P2 Receptor Antagonists
Purinergic P2 Receptors
Vasoactive Intestinal Peptide
Sensory Receptor Cells
Electric Stimulation
Nitric Oxide
Pharmaceutical Preparations

Keywords

  • Apamin
  • NANC relaxation
  • Nitric oxide
  • Proximal colon (guinea-pig)
  • Purinergic nerves

ASJC Scopus subject areas

  • Pharmacology

Cite this

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title = "Inhibition of the NANC relaxation of the guinea-pig proximal colon longitudinal muscle by the purinoceptor antagonist PPADS, inhibition of nitric oxide synthase, but not by a PACAP/VIP antagonist",
abstract = "The effects of the P2-purinoceptor antagonist pyridoxal-phosphate-6-azophenyl-2′,4′-disulphonic acid (PPADS), the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine (L-NOARG), the K+channel blocker apamin, the pituitary adenylate cyclase activating peptide (PACAP) antagonist PACAP(6-38) and the sensory neuron-blocking drug capsaicin were examined on the non-adrenergic, non-cholinergic (NANC) relaxation evoked by electrical field stimulation in the longitudinal muscle of the guinea-pig proximal colon. Both PPADS (50 μM) and L-NOARG (100 μM) significantly inhibited the NANC relaxation. In the presence of L-NOARG, PPADS inhibited and apamin (100 nM) practically abolished the response. Capsaicin slightly but significantly enhanced the NANC relaxation at 10, but not at 1 Hz stimulation frequency. PACAP(6-38) (3 μM) had no effect on the NANC relaxation, although it abolished the relaxant effect of exogenous PACAP(1-27) (10 nM) and reduced that of exogenous vasoactive intestinal polypeptide (VIP, 30-100 nM) by about 60{\%}. PPADS (50 μM) inhibited the relaxant action of exogenous adenosine 5′-triphosphate (ATP; 1 and 10 μM), the inhibition being stronger at 1 μM ATP. These data indicate that an exogenous P2-purinoceptor stimulant (possibly ATP) and NO are involved in the NANC relaxation of the guinea-pig colon. The 'non-nitrergic' apamin-sensitive component of the response might also include an unidentified transmitter. No evidence has been found for a mediating role of PACAP/VIP-like peptides.",
keywords = "Apamin, NANC relaxation, Nitric oxide, Proximal colon (guinea-pig), Purinergic nerves",
author = "Barnab{\'a}s R{\'o}zsai and Zs{\'o}fia L{\'a}z{\'a}r and R. Benk{\'o} and L. Barth{\'o}",
year = "2001",
doi = "10.1006/phrs.2000.0742",
language = "English",
volume = "43",
pages = "83--87",
journal = "Pharmacological Research",
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TY - JOUR

T1 - Inhibition of the NANC relaxation of the guinea-pig proximal colon longitudinal muscle by the purinoceptor antagonist PPADS, inhibition of nitric oxide synthase, but not by a PACAP/VIP antagonist

AU - Rózsai, Barnabás

AU - Lázár, Zsófia

AU - Benkó, R.

AU - Barthó, L.

PY - 2001

Y1 - 2001

N2 - The effects of the P2-purinoceptor antagonist pyridoxal-phosphate-6-azophenyl-2′,4′-disulphonic acid (PPADS), the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine (L-NOARG), the K+channel blocker apamin, the pituitary adenylate cyclase activating peptide (PACAP) antagonist PACAP(6-38) and the sensory neuron-blocking drug capsaicin were examined on the non-adrenergic, non-cholinergic (NANC) relaxation evoked by electrical field stimulation in the longitudinal muscle of the guinea-pig proximal colon. Both PPADS (50 μM) and L-NOARG (100 μM) significantly inhibited the NANC relaxation. In the presence of L-NOARG, PPADS inhibited and apamin (100 nM) practically abolished the response. Capsaicin slightly but significantly enhanced the NANC relaxation at 10, but not at 1 Hz stimulation frequency. PACAP(6-38) (3 μM) had no effect on the NANC relaxation, although it abolished the relaxant effect of exogenous PACAP(1-27) (10 nM) and reduced that of exogenous vasoactive intestinal polypeptide (VIP, 30-100 nM) by about 60%. PPADS (50 μM) inhibited the relaxant action of exogenous adenosine 5′-triphosphate (ATP; 1 and 10 μM), the inhibition being stronger at 1 μM ATP. These data indicate that an exogenous P2-purinoceptor stimulant (possibly ATP) and NO are involved in the NANC relaxation of the guinea-pig colon. The 'non-nitrergic' apamin-sensitive component of the response might also include an unidentified transmitter. No evidence has been found for a mediating role of PACAP/VIP-like peptides.

AB - The effects of the P2-purinoceptor antagonist pyridoxal-phosphate-6-azophenyl-2′,4′-disulphonic acid (PPADS), the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine (L-NOARG), the K+channel blocker apamin, the pituitary adenylate cyclase activating peptide (PACAP) antagonist PACAP(6-38) and the sensory neuron-blocking drug capsaicin were examined on the non-adrenergic, non-cholinergic (NANC) relaxation evoked by electrical field stimulation in the longitudinal muscle of the guinea-pig proximal colon. Both PPADS (50 μM) and L-NOARG (100 μM) significantly inhibited the NANC relaxation. In the presence of L-NOARG, PPADS inhibited and apamin (100 nM) practically abolished the response. Capsaicin slightly but significantly enhanced the NANC relaxation at 10, but not at 1 Hz stimulation frequency. PACAP(6-38) (3 μM) had no effect on the NANC relaxation, although it abolished the relaxant effect of exogenous PACAP(1-27) (10 nM) and reduced that of exogenous vasoactive intestinal polypeptide (VIP, 30-100 nM) by about 60%. PPADS (50 μM) inhibited the relaxant action of exogenous adenosine 5′-triphosphate (ATP; 1 and 10 μM), the inhibition being stronger at 1 μM ATP. These data indicate that an exogenous P2-purinoceptor stimulant (possibly ATP) and NO are involved in the NANC relaxation of the guinea-pig colon. The 'non-nitrergic' apamin-sensitive component of the response might also include an unidentified transmitter. No evidence has been found for a mediating role of PACAP/VIP-like peptides.

KW - Apamin

KW - NANC relaxation

KW - Nitric oxide

KW - Proximal colon (guinea-pig)

KW - Purinergic nerves

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U2 - 10.1006/phrs.2000.0742

DO - 10.1006/phrs.2000.0742

M3 - Article

VL - 43

SP - 83

EP - 87

JO - Pharmacological Research

JF - Pharmacological Research

SN - 1043-6618

IS - 1

ER -