ISSN:
1440-1681
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
1. In order to investigate purinergic effects on rat ileal smooth muscle, we used α,β-methylene ATP (α,β-MeATP), ATP, ADP and UTP. α,β-Methylene ATP and ATP were the only agonists that caused a concentration-dependent inhibition of carbachol-precontracted smooth muscle. The inhibitory effect of α,β-MeATP was completely blocked by pyridoxalphosphate-6-azophenyl-2′,4′-disulphonic acid (3 × 10–5 mol/L), a selective antagonist of the P2X 〉 〉 P2Y receptor.2. Using reverse transcription–polymerase chain reaction we demonstrated the presence of both, P2X and P2Y receptor mRNA within the rat ileal longitudinal muscle/myenteric plexus layer preparation.3. The α,β-MeATP-induced inhibition was blocked in a concentration-dependent manner in the presence of the K+ channel blocker apamin, but was unaffected by other K+ channel blockers, such as charybdotoxin (10–7 mol/L), 4-aminopyridine (10–4 mol/L), glibenclamide (10–5 mol/L) and tetraethylammonium (10–3 mol/L).4. The α,β-MeATP-induced inhibition was unaffected by pretreatment with atropine (10–6 mol/L), phentolamine (10–6 mol/L), propranolol (10–6 mol/L), nitrendipine (10–7 mol/L), pertussis toxin (10–6 mol/L) NG-nitro- L-arginine (3 × 10–4 mol/L) and tetrodotoxin (10–6 mol/L), excluding an involvement of adrenergic, cholinergic, neural, nitrinergic or G-protein involvement in purinergic-mediated inhibition.5. In order to investigate whether the internal Ca2+ stores participated in the inhibitory effect observed, we depleted internal Ca2+ stores with cyclopiazonic acid, a specific Ca2+-ATPase inhibitor. The inhibitory effect of α,β-MeATP was completely abolished after depletion of the intracellular Ca2+ stores.6. This is in contrast with the effects seen for neurotensin, where neurotensin-induced inhibition was unchanged after depletion of intracellular Ca2+ stores, suggesting at least two different pathways of apamin-sensitive non-adrenergic, non-cholinergic inhibition in rat ileal smooth muscle.7. According to our results, the inhibitory effect of α,β-MeATP in rat ileum longitudinal smooth muscle is mediated via a P2 purinoceptor, most likely a P2X receptor, involves G-protein-independent activation of an apamin-sensitive K+ channel and requires filled intracellular Ca2+ stores.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1440-1681.2000.03334.x
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