Veratridine-induced release of acetylcholine from mouse forebrain minces: dependence on the hydrolysis of cytoplasmic acetylcholine for a source of choline.
The importance of depolarization induced hydrolysis of cytoplasmic acetylcholine (ACh) in providing choline for the veratridine-and high K+-induced release of acetylcholine was studied in mouse forebrain minces. Results indicated that a loss of hydrolyzable cytoplasmic ACh prior to depolarization reduced the amount of ACh released by veratridine but not the amount released by high K+. The reduction in the veratridine-induced release of ACh did not occur during the first 5 min of incubation. Loss of vesicular ACh prior to depolarization reduced both the veratridine- and K+-induced release of ACh during the first 5 min of incubation. Blockade of extra-cellular choline transport by hemicholinium (HC-3) did not affect the veratridine-induced release of ACh during a 10 min incubation period unless the cytoplasmic pool of ACh had first been depleted and was unavailable as a source of choline. In contrast, HC-3 reduced the K+-induced release of ACh from brain tissue with normal stores of cytoplasmic ACh. These results indicate that both depolarizing agents primarily stimulate the release of preformed ACh from a vesicular fraction during the first 5 min of mince incubation. Thereafter, they both stimulate the release of newly synthesized ACh, however, they differ in one important respect. The principal source of choline for the veratridine-induced release of newly synthesized ACh appears to be the cytoplasmic pool of ACh, whereas the major source of choline for the K+-induced release of newly synthesized ACh appears to be extracellular choline.
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002794:Choline / Q000378:metabolism*; D004347:Drug Interactions; D006426:Hemicholinium 3 / Q000494:pharmacology; D006868:Hydrolysis; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011188:Potassium / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology*; D014702:Veratrine / Q000031:analogs & derivatives*
D006426:Hemicholinium 3; D014701:Veratridine; D014702:Veratrine; D002794:Choline; D000109:Acetylcholine; D011188:Potassium