Cited by 314Receptor Mechanisms and SignalingNeuroscience and Neuropharmacology ResearchNeurotransmitter Receptor Influence on Behavior

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

Raiteri, M, Leardi, R, Marchi, M·1984·The Journal of Pharmacology and Experimental Therapeutics

DOI 10.1016/s0022-3565(25)21528-2

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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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Self-citation
Glucose enhancement of scopolamine-induced increase of hippocampal high-affinity choline uptake in mice: relation to plasma glucose levels
Micheau, J., Messier, C., & Jaffard, R. (1995) · Brain Research · doi:10.1016/0006-8993(95)00415-m · Cited by 19
Muscarinic receptors acting at pre- and post-synaptic sites differentially regulate dopamine/DARPP-32 signaling in striatonigral and striatopallidal neurons
Kuroiwa, M., Hamada, M., Hieda, E., Shuto, T., Sotogaku, N., Flajolet, M., Snyder, G. L., Hendrick, J. P., Fienberg, A. A., & Nishi, A. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.07.046 · Cited by 19
“Pharmacological studies using a relatively selective M1 antagonist, pirenzepine, have suggested the stimulatory role of M1 receptors in dopamine release in the striatum (Raiteri et al., 1984; Xu et al., 1989; De Klippel et al., 1993; Smolders et al., 1997).”
Background
Cholinergic stimulation of drinking from the lateral hypothalamus: Indications for M2 muscarinic receptor mediation
Hagan, J. (1987) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(87)90610-1 · Cited by 19
Altered Striatal Dopaminergic and Cholinergic Reciprocal Inhibitory Control and Motor Behavioral Decrements in Senescence
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Critical role of CA1 muscarinic receptors on memory acquisition deficit induced by total (TSD) and REM sleep deprivation (RSD)
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Scopolamine induces up-regulation of nicotinic receptors in intact brain but not in nucleus basalis lesioned rats
Vigé, X., & Briley, M. (1988) · Neuroscience Letters · doi:10.1016/0304-3940(88)90231-5 · Cited by 18
Effect of Unilateral Perinatal Hypoxic‐Ischemic Brain Injury in the Rat on Striatal Muscarinic Cholinergic Receptors and High‐Affinity Choline Uptake Sites: A Quantitative Autoradiographic Study
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Pharmacological activity of N-methyl-carbamylcholine, a novel acetylcholine receptor agonist with selectivity for nicotinic receptors
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Muscarinic ml receptors in the lateral septal area mediate cardiovascular responses to cholinergic agonists and bradykinin: supersensitivity induced by chronic treatment with atropine
Scheucher, A., Pirola, C. J., Balda, M. S., et al. (1987) · Neuropharmacology · doi:10.1016/0028-3908(87)90207-3 · Cited by 18
Differential antagonism by dicyclomine, pirenzepine and secoverine at muscarinic receptor subtypes in the rat frontal cortex
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Secoverine is a non-selective muscarinic antagonist on rat heart and brain receptors
Brünner, F., Waelbroeck, M., & Christophe, J. (1986) · European Journal of Pharmacology · doi:10.1016/0014-2999(86)90201-3 · Cited by 18
Role of Receptor Coupling to Phosphoinositide Metabolism in the Therapeutic Action of Lithium
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Pharmacological Characterization of Endogenous Acetylcholine Release from Primary Septal Cultures
Auld, D. S., Day, J. C., Mennicken, F., & Quirion, R. (2000) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)35340-6 · Cited by 16
Is the effect of somatostatin on muscarinic receptors selective to M1 type?
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Cholinergic modulation of [3H]dopamine release from dendrosomes of rat substantia nigra
Marchi, M., Augliera, A., Codignola, A., et al. (1991) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/bf00183000 · Cited by 17
“Crude P2 fractions were prepared as previously described (Gray and Whittaker 1962; Raiteri et al. 1984).”
BackgroundMethodResultInfluentialSelf-citation

Authors: Raiteri, M., Leardi, R., & Marchi, M.
ORCID: Leardi, R
Marchi, M
Venue: The Journal of Pharmacology and Experimental Therapeutics
Publisher: Elsevier BV
Published: 1984-01
Volume: 228
Issue: 1
Pages: 209-214
ISSN: 0022-3565 (ISSN-L)
DOI: 10.1016/s0022-3565(25)21528-2
OpenAlex: W1927364971
Cited by: 314
References: 0
Citations by year: 2025: 3 · 2024: 2 · 2022: 1 · 2021: 2 · 2018: 2 · 2017: 5 · 2016: 5 · 2015: 4 · 2013: 4 · 2012: 4
FWCI: 8.35
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
PubMed (publishedVersion)
PubMed
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords: presynaptic muscarinic receptors, muscarinic autoreceptors, neurotransmitter release, acetylcholine release, dopamine release, striatum, hippocampus, cerebral cortex, oxotremorine, carbachol, pirenzepine, atropine, antimuscarinic agents, receptor heterogeneity
MeSH terms: Acetylcholine, Animals, Brain, Cerebral Cortex, Corpus Striatum, Dopamine, Hippocampus, Male, Parasympatholytics, Parasympathomimetics, Rats, Inbred Strains, Receptors, Muscarinic, Synaptosomes, Time Factors, Neurotransmitter Agents, Rats, In Vitro Techniques

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

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