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.
Suzuki
T
T
Department of Pharmacology, Kyoritsu College of Pharmacy, Tokyo, Japan.
Fujimoto
K
K
Oohata
H
H
Kawashima
K
K
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects*; D008297:Male; D011188:Potassium / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology*
D014150:Antipsychotic Agents; D013973:Thyrotropin-Releasing Hormone; C029762:DN 1417; D000109:Acetylcholine; D011188:Potassium