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Abstract

Heterogeneity of presynaptic muscarinic receptors regulating neurotransmitter release in the rat brain.

M Raiteri, R Leardi and M Marchi
Journal of Pharmacology and Experimental Therapeutics January 1984, 228 (1) 209-214;
M Raiteri
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R Leardi
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M Marchi
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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 three systems of release regulation mediated by presynaptic muscarinic receptors. The receptors selected as models for our experiments were: 1) the muscarinic autoreceptors mediating inhibition of acetylcholine release in the cortex; 2) the muscarinic autoreceptors present in the nerve endings of the hippocampus; and 3) the muscarinic presynaptic receptors mediating potentiation of striatal dopamine release (heteroreceptors). The experiments were performed by using rat brain synaptosomes in superfusion. Acetylcholine, oxotremorine and carbachol inhibited the release of [3H]acetylcholine evoked by 15 mM KCI in cortex and hippocampus and potentiated the K+-evoked [3H]dopamine release in the striatum. The concentration-response curves were similar in the three systems, the rank of potency being: acetylcholine greater than oxotremorine greater than carbachol. The effects of acetylcholine were counteracted by several muscarinic antagonists with different rank of potencies and different potency ratios. In particular, the rank of potencies for the drugs tested was: atropine greater than secoverine greater than stercuronium greater than pirenzepine at the autoreceptors, both in cortex and hippocampus; but it was: atropine greater than pirenzepine = secoverine greater than stercuronium, at the heteroreceptors in the striatum. Pirenzepine was 100 times more potent on heteroreceptors than on autoreceptors. Our results suggest the possibility of a differential activation or blockade of central muscarinic receptors by selective drugs.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 228, Issue 1
1 Jan 1984
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Abstract

Heterogeneity of presynaptic muscarinic receptors regulating neurotransmitter release in the rat brain.

M Raiteri, R Leardi and M Marchi
Journal of Pharmacology and Experimental Therapeutics January 1, 1984, 228 (1) 209-214;

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Abstract

Heterogeneity of presynaptic muscarinic receptors regulating neurotransmitter release in the rat brain.

M Raiteri, R Leardi and M Marchi
Journal of Pharmacology and Experimental Therapeutics January 1, 1984, 228 (1) 209-214;
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