Characterization of Presynaptic Muscarinic Receptors in Central Cholinergic Neurons
It is now well established that anticholinergic agents such as atropine increase the evoked release of ACh from the cerebral cortex in vivo (15, 22) and from cortical slices in vitro (2, 3). At a previous symposium on cholinergic mechanisms (23), observations were summarized which indicated that this enhancement of ACh release by antimuscarinic agents is the result of their overcoming the inhibitory effect of ACh which accumulates in unphysiologically high concentrations when a ChE inhibitor is used to prevent the hydrolysis of ACh (23). Evidence for this was obtained by measuring the evoked release of labelled ACh without inhibiting ChE (18, 21). The rate of evoked release of the label was reduced when a ChE inhibitor was present and restored when atropine was also added (3, 25). Our recent experiments attempted to answer the following questions: 1) Does the inhibitory effect of a ChE inhibitor require the presence of cell bodies of cholinergic neurons on release, or is this an effect on the terminals? 2) Has this feedback inhibition a physiological role, i. e. does it occur in the absence of ChE inhibition? 3) What is the sensitivity of this feedback inhibition to muscarinic agonists and antagonists?
KeywordsMedial Septum Muscarinic Agonist Postsynaptic Receptor Cholinergic Mechanism Presynaptic Receptor
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