ADENYLATE-CYCLASE IN STRIATAL CHOLINERGIC INTERNEURONS REGULATES ACETYLCHOLINE-RELEASE

Fractional [H-3]ACH efflux from dissociated rat striata tested whether tonic inhibition prevents stimulation of acetylcholine (AGH) release by adenylate cyclase. Forskolin stimulated release from the dissociate d cells (threshold at 300 nM; EC(50) greater than or equal to 1 mu M). Release was also stimulated by 3-isobutyl-1-methylxanthine and was ad ditive with forskolin. The 1,9-dideoxy forskolin analog that lacks cyc lase-stimulating activity was ineffective. Thus, stimulation of adenyl ate cyclase within striatal cholinergic interneurons increases ACH sec retion but is tonically inhibited by endogenous striatal transmitters. Disinhibition of the excitatory cyclase by denervation of striatal ch olinergic interneurons in situ could contribute to supersensitivity wi thout receptor upregulation.