title: Inhibition of choline efflux results in enhanced acetylcholine synthesis and release in the guinea-pig corticocerebral synaptosomes.
abstract: Synthesis and release of [3H]acetylcholine ([3H]ACh) were measured in synaptosomes from the guinea pig cerebral cortex after preloading with [3H]choline ([3H]Ch). We demonstrate here that inhibition of choline (Ch) efflux results in an increase in acetylcholine (ACh) synthesis and release. Our findings are as follows: (1) inhibition of [3H]Ch efflux by hemicholinium-3 (HC-3) (100 microM), increased the levels of both the released (116% of control) and the residing (115% of control) [3H]ACh. (2) The muscarinic agonist, McN-A-343 (100 microM), which was previously shown to inhibit Ch efflux, also increased the released (121% of control) and the residing (109% of control) [3H]ACh. (3) Omission of Na+ ions (which are required for Ch transport) from the incubation medium had similar effects to those observed with McN-A-343 and HC-3. These results suggest inverse relationships between Ch efflux on one hand, and ACh synthesis and release on the other hand. (4) Depolarization with 50 mM K+, or with the K+ channel blocker, 4-aminopyridine (100 microM), also increased the total level of [3H]ACh (113 and 107% of nondepolarized synaptosomes, respectively). However, whereas conditions that inhibit Ch transport such as HC-3, McN-A-343 and "no sodium" increased both the residing and the released [3H]ACh depolarization with high K+ or 4-aminopyridine reduced the residing (79 and 87% of control, respectively) and increased only the released [3H]ACh (182 and 148% of control, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Israel Institute for Biological Research, Ness-Ziona.
authors.forename: Z
authors.initials: Z
authors.lastname: Pittel
authors.forename: E
authors.initials: E
authors.lastname: Heldman
authors.forename: R
authors.initials: R
authors.lastname: Rubinstein
authors.forename: S
authors.initials: S
authors.lastname: Cohen
mesh_terms: D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride / Q000494:pharmacology; D000109:Acetylcholine / Q000096:biosynthesis / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D002794:Choline / Q000378:metabolism*; D006168:Guinea Pigs; D006426:Hemicholinium 3 / Q000494:pharmacology*; D007700:Kinetics; D026901:Membrane Transport Proteins; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D014316:Tritium
chemical_list: D002352:Carrier Proteins; D026901:Membrane Transport Proteins; C065637:choline transporter; D014316:Tritium; D006426:Hemicholinium 3; D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride; D002794:Choline; D000109:Acetylcholine