Activation of adenosine A1 and A2 receptors differentially affects acetylcholine release from electric organ synaptosomes by modulating calcium channels.
Adenosine inhibited the release of acetylcholine (ACh) evoked by high K+ depolarization from synaptosomes isolated from the electric organ of the Japanese electric ray Narke japonica. The adenosine A1 receptor agonist N6-cyclohexyladenosine was an effective inhibitor. Conversely, in the presence of an A1 receptor antagonist, 8-cyclopentyltheophylline, adenosine potentiated the release of ACh. The A2 receptor agonist N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)ethyl] adenosine also facilitated the evoked ACh release. Thus, adenosine inhibits the evoked release of ACh via the A1 receptor while it facilitates the release via the A2 receptor. The EC50 for inhibition and facilitation by adenosine was about 1 and 41 microM, respectively. There are three known types of calcium channels (N-, P/Q- and L-type) in synaptosomes. The effects of Ca2+ channel type-specific blockers on the modulation of ACh release by adenosine A1 or A2 receptor activation revealed that inhibition by A1 receptor activation was caused via inhibition of N-type calcium channels and the facilitative effects by A2 receptor activation was mediated by potentiation of P-type calcium channels.
Satoh
Y
Y
Laboratory of Neurobiophysics, School of Pharmaceutical Sciences, The University of Tokyo, Japan.
Hirashima
N
N
Tokumaru
H
H
Kirino
Y
Y
D000109:Acetylcholine / Q000378:metabolism*; D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000502:physiology*; D058906:Purinergic P1 Receptor Agonists; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D013574:Synaptosomes / Q000187:drug effects / Q000502:physiology*; D014101:Torpedo
D015220:Calcium Channels; D058906:Purinergic P1 Receptor Agonists; D018047:Receptors, Purinergic P1; D000241:Adenosine; D000109:Acetylcholine