LY 294002 inhibits adenosine receptor activation by a mechanism independent of effects on PI-3 kinase or casein kinase II.

Purinergic Signalling
T J Searl, E M Silinsky

Abstract

Adenosine reduces both evoked and spontaneous calcium-dependent acetylcholine (ACh) release through a mechanism downstream of calcium entry at amphibian motor nerve endings (Silinsky EM. J Physiol 1984; 346: 243-56). LY 294002 (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one), an inhibitor of both phosphoinositide-3 kinase (PI-3 kinase) and casein kinase II, has been reported to increase spontaneous ACh release reflected in miniature endplate potential (MEPP) frequencies independently of intraterminal calcium at the frog neuromuscular junction (Rizzoli SO, Betz WJ. J Neurosci 2002; 22: 10680-9). It has been suggested that the increase in MEPP frequency caused by LY 294002, is mediated through an action on synaptotagmins, vesicle associated calcium sensors believed to trigger synaptic vesicle exocytosis. We thus examined the effects of adenosine on MEPP frequencies and evoked ACh release reflected as endplate potentials (EPPs) in order to determine if the presumed calcium-independent ACh release is affected by adenosine. We also wanted to determine if PI-3 kinase or casein kinase II is involved in mediating or modulating the inhibitory effects of adenosine. To these ends, we examined the effects of adenosine in the presence of ...Continue Reading

References

Jan 12, 1990·European Journal of Biochemistry·F MeggioL A Pinna
Oct 1, 1993·British Journal of Pharmacology·J M Hunt, E M Silinsky
Nov 7, 1999·Progress in Brain Research·E M SilinskyM Watanabe
Nov 24, 1999·Canadian Journal of Physiology and Pharmacology·R RobitailleM P Charlton
Jun 24, 2000·British Journal of Pharmacology·R Germack, J M Dickenson
Sep 22, 2000·The Biochemical Journal·S P DaviesP Cohen

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