To study the regulation of striatal acetylcholine (ACH) release, adult
male rat striata were dissociated and incubated with 3H-choline to sy
nthesize 3H-ACH. Fractional 3H-ACH efflux per min during continuous pe
rifusion was: (1) tightly regulated; (2) dependent on calcium influx;
(3) stimulated by 10 mM K+ and 1 mM glutamate; and (4) comparable to A
CH release detected by HPLC. Thus, acutely dissociated striata exhibit
calcium-sensitive, voltage-dependent secretion of 3H-ACH and direct r
eceptor-mediated stimulation of release through the glutamate receptor
family. This new approach toward cholinergic secretory physiology wil
l help clarify complex striatal circuitry.