Mode of action of palytoxin on the release of acetylcholine from rat cerebrocortical synaptosomes.
Palytoxin (PTX; 10(-14)-10(-6) M) caused a dose-dependent increase in the release of [3H]acetylcholine ([3H]ACh), cytosolic free Ca2+ concentration ([Ca2+]i), and uptake of 22Na+ and decrease in membrane potential in rat cerebrocortical synaptosomes. The dose-response curves for the PTX-induced increases in [3H]ACh release and in [Ca2+]i were depressed by removing extracellular Ca2+ or by decreasing extracellular Na+ concentrations. The release of [3H]ACh induced by concentrations of PTX less than 10(-10) M was more dependent on the simultaneous presence of both Ca2+ and Na+ than the release induced by higher concentrations of PTX. The PTX-induced increase both in [3H]ACh release and in [Ca2+]i was almost completely abolished by the combination of Ca2+ deprivation and Na+ concentration reduction. All responses to PTX were highly resistant to 10(-6) M tetrodotoxin. These results suggest that low concentrations of PTX cause depolarization as a result of an increase in Na+ permeability through tetrodotoxin-insensitive channels. This, in turn, increases Ca2+ influx and leads to an increase in the release of ACh. It appears that at high concentrations PTX increases the release of [3H]ACh by directly increasing the influx of Ca2+ into synaptosomes and by releasing Ca2+ from intracellular storage sites via an Na(+)-Ca2+ exchange mechanism.
Department of Veterinary Pharmacology, Obihiro University of Agriculture and Veterinary Medicine, Japan.
E
E
Satoh
Y
Y
Nakazato
D000109:Acetylcholine / Q000378:metabolism*; D000178:Acrylamides; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism* / Q000502:physiology; D003064:Cnidarian Venoms / Q000494:pharmacology*; D005110:Extracellular Space / Q000378:metabolism; D008564:Membrane Potentials; D009994:Osmolar Concentration; D051381:Rats; D012964:Sodium / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism* / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D000095702:Polyether Toxins
D000109:Acetylcholine; D000178:Acrylamides; D002118:Calcium; D003064:Cnidarian Venoms; D012964:Sodium; D013779:Tetrodotoxin; C010272:palytoxin; D000095702:Polyether Toxins