HETEROGENEITY OF PRESYNAPTIC MUSCARINIC RECEPTORS REGULATING NEUROTRANSMITTER RELEASE IN THE RAT-BRAIN

  • 1 January 1984
    • journal article
    • research article
    • Vol. 228  (1) , 209-214
Abstract
The existence of multiple muscarinic receptors in the brain was investigated by using neurotransmitter release as a functional parameter and by comparing the effects of agonists and antagonists on 3 systems of release regulation mediated by presynaptic muscarinic receptors. The receptors selected as models for the experiments were: the muscarinic autoreceptors mediating inhibition of acetylcholine release in the cortex; the muscarinic autoreceptors present in the nerve endings of the hippocampus; and the muscarinic presynaptic receptors mediating potentiation of striatal dopamine release (heteroreceptors). Rat brain synaptosomes in superfusion were used. Acetylcholine, oxotremorine and carbachol inhibited the release of [3H]acetylcholine evoked by 15 mM KCl in cortex and hippocampus and potentiated the K+-evoked [3H]dopamine release in the striatum. The concentration-response curves were similar in the 3 systems, the rank of potency being acetylcholine > oxotremorine > carbachol. The effects of acetylcholine were counteracted by several muscarinic antagonists with different rank of potencies and different potency ratios. The rank of potencies for the drugs tested was atropine > secoverine > stercuronium > pirenzepine at the autoreceptors, both in cortex and hippocampus; it was atropine > pirenzepine = secoverine > stercuronium at the heteroreceptors in the striatum. Pirenzepine was 100 times more potent on heteroreceptors than on autoreceptors. The possibility of a differential activation or blockade of central muscarinic receptors by selective drugs is suggested.

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