Action of suramin upon ecto-apyrase activity and synaptic depression of Torpedo electric organ.
1. The role of ATP, which is co-released with acetylcholine in synaptic contacts of Torpedo electric organ, was investigated by use of suramin. Suramin [8-(3-benzamido-4-methylbenzamido)naphthalene-1,3,5-trisulphoni c acid], a P2 purinoceptor antagonist, potently inhibited in a non-competitive manner the ecto-apyrase activity associated with plasma membrane isolated from cholinergic nerve terminals of Torpedo electric organ. The Ki was 30 microM and 43 microM for Ca(2+)-ADPase and Ca(2+)-ATPase respectively. 2. In Torpedo electric organ, repetitive stimulation decreased the evoked synaptic current by 51%. However, when fragments of electric organ were incubated with suramin the evoked synaptic current declined by only 14%. Fragments incubated with the selective A1 purinoceptor antagonist, DPCPX, showed 5% synaptic depression. 3. The effects of suramin and DPCPX on synaptic depression were not addictive. Synaptic depression may thus be linked to endogenous adenosine formed by dephosphorylation of released ATP by an ecto-apyrase. The final effector in synaptic depression, adenosine, acts via the A1 purinoceptor. 4. ATP hydrolysis is prevented in the presence of suramin. It slightly increased (20%) the mean amplitude of spontaneous miniature endplate currents. The frequency distribution of the amplitude of spontaneous events was shifted to the right, indicating that ATP, when not degraded, may modulate the activation of nicotinic acetylcholine receptors activated by the quantal secretion of acetycholine.
Martí
E
E
Departament de Biologia Cellular i Anatomia Patològica, Facultat de Medicina, Hospital de Bellvitge, Universitat de Barcelona, L'Hospitalet de Llobregat, Spain.
Cantí
C
C
Gómez de Aranda
I
I
Miralles
F
F
Solsona
C
C
D000109:Acetylcholine / Q000502:physiology; D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001081:Apyrase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002462:Cell Membrane / Q000502:physiology; D004557:Electric Organ / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D004594:Electrophysiology; D008564:Membrane Potentials / Q000187:drug effects; D009045:Motor Endplate / Q000187:drug effects; D009411:Nerve Endings / Q000187:drug effects; D009469:Neuromuscular Junction / Q000502:physiology; D011950:Receptors, Cholinergic / Q000502:physiology; D013498:Suramin / Q000494:pharmacology*; D009435:Synaptic Transmission; D014101:Torpedo; D014970:Xanthines / Q000494:pharmacology
D011950:Receptors, Cholinergic; D014970:Xanthines; D013498:Suramin; D000255:Adenosine Triphosphate; C051360:1,3-dipropyl-8-cyclopentylxanthine; D001081:Apyrase; D000109:Acetylcholine