A1 receptors mediate adenosine inhibitory effects in mouse ileum via activation of potassium channels

Rosa Maria Serio, Flavia Mule', Maria Grazia Zizzo, Natale Belluardo, Maria Grazia Zizzo, Flavia Mulè, Rosa Serio, Alessandra Bonomo

Risultato della ricerca: Article

16 Citazioni (Scopus)

Abstract

AimsWe investigated the effects induced by exogenous adenosine on the spontaneous contractile activity of the longitudinal muscle of a mouse ileum, the receptor subtypes activated, the involvement of enteric nerves and whether opening of K+ channels was a downstream event leading to the observed effects.Main methodsMechanical responses of the mouse ileal longitudinal muscle to adenosine were examined in vitro as changes in isometric tension.Key findingsAdenosine caused a concentration-dependent reduction of the spontaneous contraction amplitude of the ileal longitudinal muscle up to its complete disappearance. This effect induced was markedly reduced by an A1 receptor antagonist, but not by A2 and A3 receptor antagonists and mimicked only by the A1 receptor agonist. Adenosine uptake inhibitors did not change adenosine potency. A1 receptor expression was detected at the smooth muscle level. Adenosine responses were insensitive to tetrodotoxin, atropine or nitric oxide synthase inhibitor. Tetraethylammonium and iberiotoxin, BKCa channel blockers, significantly reduced adenosine effects, whilst 4-aminopyridine, a Kv blocker, apamin, a small conductance Ca2+-activated K+ (SKCa) channel blocker, charybdotoxin, an intermediate conductance Ca2+-activated K+ (IKCa) and BKCa channel blocker, or glibenclamide, an ATP-sensitive K+ channel blocker, had no effects. The combination of apamin plus iberiotoxin caused a reduction of the purinergic effects greater than iberiotoxin alone.SignificanceAdenosine acts as an inhibitory modulator of the contractility of mouse ileal longitudinal muscle through postjunctional A1 receptors, which in turn would induce opening of BKCa and SKCa potassium channels. This study would provide new insight in the pharmacology of purinergic receptors involved in the modulation of the gastrointestinal contractility.
Lingua originaleEnglish
pagine (da-a)772-778
Numero di pagine8
RivistaLife Sciences
Volume84
Stato di pubblicazionePublished - 2009

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Adenosine A1 Receptors
Potassium Channels
Ileum
Adenosine
Chemical activation
Muscle
Apamin
Muscles
Purinergic Agents
Charybdotoxin
Purinergic Receptors
Calcium-Activated Potassium Channels
4-Aminopyridine
Tetraethylammonium
Glyburide
Tetrodotoxin
Atropine
varespladib methyl
Nitric Oxide Synthase
Modulators

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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A1 receptors mediate adenosine inhibitory effects in mouse ileum via activation of potassium channels. / Serio, Rosa Maria; Mule', Flavia; Zizzo, Maria Grazia; Belluardo, Natale; Zizzo, Maria Grazia; Mulè, Flavia; Serio, Rosa; Bonomo, Alessandra.

In: Life Sciences, Vol. 84, 2009, pag. 772-778.

Risultato della ricerca: Article

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title = "A1 receptors mediate adenosine inhibitory effects in mouse ileum via activation of potassium channels",
abstract = "AimsWe investigated the effects induced by exogenous adenosine on the spontaneous contractile activity of the longitudinal muscle of a mouse ileum, the receptor subtypes activated, the involvement of enteric nerves and whether opening of K+ channels was a downstream event leading to the observed effects.Main methodsMechanical responses of the mouse ileal longitudinal muscle to adenosine were examined in vitro as changes in isometric tension.Key findingsAdenosine caused a concentration-dependent reduction of the spontaneous contraction amplitude of the ileal longitudinal muscle up to its complete disappearance. This effect induced was markedly reduced by an A1 receptor antagonist, but not by A2 and A3 receptor antagonists and mimicked only by the A1 receptor agonist. Adenosine uptake inhibitors did not change adenosine potency. A1 receptor expression was detected at the smooth muscle level. Adenosine responses were insensitive to tetrodotoxin, atropine or nitric oxide synthase inhibitor. Tetraethylammonium and iberiotoxin, BKCa channel blockers, significantly reduced adenosine effects, whilst 4-aminopyridine, a Kv blocker, apamin, a small conductance Ca2+-activated K+ (SKCa) channel blocker, charybdotoxin, an intermediate conductance Ca2+-activated K+ (IKCa) and BKCa channel blocker, or glibenclamide, an ATP-sensitive K+ channel blocker, had no effects. The combination of apamin plus iberiotoxin caused a reduction of the purinergic effects greater than iberiotoxin alone.SignificanceAdenosine acts as an inhibitory modulator of the contractility of mouse ileal longitudinal muscle through postjunctional A1 receptors, which in turn would induce opening of BKCa and SKCa potassium channels. This study would provide new insight in the pharmacology of purinergic receptors involved in the modulation of the gastrointestinal contractility.",
keywords = "Adenosine, Mechanical activity, Mouse ileum, P1 purinoceptors",
author = "Serio, {Rosa Maria} and Flavia Mule' and Zizzo, {Maria Grazia} and Natale Belluardo and Zizzo, {Maria Grazia} and Flavia Mul{\`e} and Rosa Serio and Alessandra Bonomo",
year = "2009",
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volume = "84",
pages = "772--778",
journal = "Life Sciences",
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TY - JOUR

T1 - A1 receptors mediate adenosine inhibitory effects in mouse ileum via activation of potassium channels

AU - Serio, Rosa Maria

AU - Mule', Flavia

AU - Zizzo, Maria Grazia

AU - Belluardo, Natale

AU - Zizzo, Maria Grazia

AU - Mulè, Flavia

AU - Serio, Rosa

AU - Bonomo, Alessandra

PY - 2009

Y1 - 2009

N2 - AimsWe investigated the effects induced by exogenous adenosine on the spontaneous contractile activity of the longitudinal muscle of a mouse ileum, the receptor subtypes activated, the involvement of enteric nerves and whether opening of K+ channels was a downstream event leading to the observed effects.Main methodsMechanical responses of the mouse ileal longitudinal muscle to adenosine were examined in vitro as changes in isometric tension.Key findingsAdenosine caused a concentration-dependent reduction of the spontaneous contraction amplitude of the ileal longitudinal muscle up to its complete disappearance. This effect induced was markedly reduced by an A1 receptor antagonist, but not by A2 and A3 receptor antagonists and mimicked only by the A1 receptor agonist. Adenosine uptake inhibitors did not change adenosine potency. A1 receptor expression was detected at the smooth muscle level. Adenosine responses were insensitive to tetrodotoxin, atropine or nitric oxide synthase inhibitor. Tetraethylammonium and iberiotoxin, BKCa channel blockers, significantly reduced adenosine effects, whilst 4-aminopyridine, a Kv blocker, apamin, a small conductance Ca2+-activated K+ (SKCa) channel blocker, charybdotoxin, an intermediate conductance Ca2+-activated K+ (IKCa) and BKCa channel blocker, or glibenclamide, an ATP-sensitive K+ channel blocker, had no effects. The combination of apamin plus iberiotoxin caused a reduction of the purinergic effects greater than iberiotoxin alone.SignificanceAdenosine acts as an inhibitory modulator of the contractility of mouse ileal longitudinal muscle through postjunctional A1 receptors, which in turn would induce opening of BKCa and SKCa potassium channels. This study would provide new insight in the pharmacology of purinergic receptors involved in the modulation of the gastrointestinal contractility.

AB - AimsWe investigated the effects induced by exogenous adenosine on the spontaneous contractile activity of the longitudinal muscle of a mouse ileum, the receptor subtypes activated, the involvement of enteric nerves and whether opening of K+ channels was a downstream event leading to the observed effects.Main methodsMechanical responses of the mouse ileal longitudinal muscle to adenosine were examined in vitro as changes in isometric tension.Key findingsAdenosine caused a concentration-dependent reduction of the spontaneous contraction amplitude of the ileal longitudinal muscle up to its complete disappearance. This effect induced was markedly reduced by an A1 receptor antagonist, but not by A2 and A3 receptor antagonists and mimicked only by the A1 receptor agonist. Adenosine uptake inhibitors did not change adenosine potency. A1 receptor expression was detected at the smooth muscle level. Adenosine responses were insensitive to tetrodotoxin, atropine or nitric oxide synthase inhibitor. Tetraethylammonium and iberiotoxin, BKCa channel blockers, significantly reduced adenosine effects, whilst 4-aminopyridine, a Kv blocker, apamin, a small conductance Ca2+-activated K+ (SKCa) channel blocker, charybdotoxin, an intermediate conductance Ca2+-activated K+ (IKCa) and BKCa channel blocker, or glibenclamide, an ATP-sensitive K+ channel blocker, had no effects. The combination of apamin plus iberiotoxin caused a reduction of the purinergic effects greater than iberiotoxin alone.SignificanceAdenosine acts as an inhibitory modulator of the contractility of mouse ileal longitudinal muscle through postjunctional A1 receptors, which in turn would induce opening of BKCa and SKCa potassium channels. This study would provide new insight in the pharmacology of purinergic receptors involved in the modulation of the gastrointestinal contractility.

KW - Adenosine

KW - Mechanical activity

KW - Mouse ileum

KW - P1 purinoceptors

UR - http://hdl.handle.net/10447/35320

M3 - Article

VL - 84

SP - 772

EP - 778

JO - Life Sciences

JF - Life Sciences

SN - 0024-3205

ER -