Muscarinic modulation of endogenous acetylcholine release in rat neostriatal slices

Some classical and nonclassical muscarinic agents were tested for their effects on potassium-evoked acetylcholine (ACh) release from rat neostriatal slices. Release was monitored by measuring endogenous ACh when acetylcholinesterase (AChE) was inhibited with physostigmine (30 microM) or by measuring endogenous choline when AChE activity was left intact. The classical antagonist, atropine (0.1-2 microM), induced an increase in release whether AChE activity was inhibited or intact. The putative M-1 selective antagonist, pirenzepine, had minimal effects over a broad concentration range (2-200 microM) and induced an increase in ACh release only when AChE activity was inhibited. The classical agonist, oxotremorine (10-100 microM) decreased effectively ACh release (by 22-35%), but only when AChE activity was intact. The oxotremorine analog, oxotremorine-M, was apparently more potent than oxotremorine, but also decreased ACh release (by 24-41%) only when AChE activity was intact. Another oxotremorine analog, BM-5, behaved more like a muscarinic antagonist in its effects on neostriatal ACh release, and the highest concentration tested (100 microM) increased release (by 47%) when AChE activity was left intact. As in many other cholinergic systems, the agonists tested in this study were not selective in their action on ACh release modulation in the rat neostriatum. The antagonists, however, were more selective in their action, i.e., pirenzepine was relatively ineffective, and on the basis of this selective action, it can be concluded that modulation of endogenous ACh release in the rat neostriatum is mediated by a M-2 muscarinic receptor subtype.