Effects of TRH and DN-1417 on high potassium-evoked acetylcholine release from rat basal forebrain slices determined directly by radioimmunoassay.

1. High potassium (50 mM)-evoked acetylcholine (ACh) release from rat basal forebrain slices under conditions without an exogenous choline supply was determined using a radioimmunoassay for ACh. 2. A consistent amount of ACh release was observed at each repetitive stimulation and ACh content in brain slices was not altered by potassium stimulations. These results indicate the existence of a large intracellular releasable ACh store, which is independent of new synthesis from exogenous choline. 3. Atropine, even at a concentration of 10(-6) M, did not affect the potassium-evoked ACh release. Thus, modulation of ACh release by the muscarinic autoreceptor was not revealed under the conditions employed. 4. Thyrotropin-releasing hormone (TRH, 10(-4) M) caused a slight and statistically insignificant increase in potassium-evoked ACh release. DN-1417, a TRH analogue, at a concentration of 10(-4) M significantly increased potassium-evoked ACh release. These findings indicate that DN-1417 is able to enhance ACh output independently of ACh synthesis from exogenous choline.