Tags

Type your tag names separated by a space and hit enter

Nicotinic autoreceptors mediating enhancement of acetylcholine release become operative in conditions of "impaired" cholinergic presynaptic function.
J Neurochem. 1996 Nov; 67(5):1974-81.JN

Abstract

The existence in the mammalian CNS of release-inhibiting muscarinic autoreceptors is well established. In contrast, few reports have focused on nicotinic autoreceptors mediating enhancement of acetylcholine (ACh) release. Moreover, it is unclear under what conditions the function of one type of autoreceptor prevails over that of the other. Rat cerebrocortex slices, prelabeled with [3H]choline, were stimulated electrically at 3 or 0.1 Hz. The release of [3H]ACh evoked at both frequencies was inhibited by oxotremorine, a muscarinic receptor agonist, and stimulated by atropine, a muscarinic antagonist. Nicotine, ineffective at 3 Hz, enhanced [3H]ACh release at 0.1 Hz; mecamylamine, a nicotinic antagonist, had no effect at 3 Hz but inhibited [3H]ACh release at 0.1 Hz. The cholinesterase inhibitor neostigmine decreased [3H]ACh release at 3 Hz but not at 0.1 Hz; in the presence of atropine, neostigmine potentiated [3H]ACh release, an effect blocked by mecamylamine. In synaptosomes depolarized with 15 mM KCl, ACh inhibited [3H]ACh release; this inhibition was reversed to an enhancement when the external [Ca2+] was lowered. The same occurred when, at 1.2 mM Ca2+, external [K+] was decreased. Oxotremorine still inhibited [3H]ACh release at 0.1 mM Ca2+. When muscarinic receptors were inactivated with atropine, the K+ (15 mM)-evoked release of [3H]ACh (at 0.1 mM Ca2+) was potently enhanced by ACh acting at nicotinic receptors (EC50 approximately 0.6 microM). In conclusion, synaptic ACh concentration does not seem to determine whether muscarinic or nicotinic autoreceptors are activated. Although muscarinic autoreceptors prevail under normal conditions, nicotinic autoreceptors appear to become responsive to endogenous ACh and to exogenous nicotinic agents under conditions mimicking impairment of ACh release. Our data may explain in part the reported efficacy of cholinesterase inhibitors (and nicotinic agonists) in Alzheimer's disease.

Authors+Show Affiliations

Istituto di Farmacologia e Farmacognosia, Università di Genova, Italy.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

8863503

Citation

Marchi, M, and M Raiteri. "Nicotinic Autoreceptors Mediating Enhancement of Acetylcholine Release Become Operative in Conditions of "impaired" Cholinergic Presynaptic Function." Journal of Neurochemistry, vol. 67, no. 5, 1996, pp. 1974-81.
Marchi M, Raiteri M. Nicotinic autoreceptors mediating enhancement of acetylcholine release become operative in conditions of "impaired" cholinergic presynaptic function. J Neurochem. 1996;67(5):1974-81.
Marchi, M., & Raiteri, M. (1996). Nicotinic autoreceptors mediating enhancement of acetylcholine release become operative in conditions of "impaired" cholinergic presynaptic function. Journal of Neurochemistry, 67(5), 1974-81.
Marchi M, Raiteri M. Nicotinic Autoreceptors Mediating Enhancement of Acetylcholine Release Become Operative in Conditions of "impaired" Cholinergic Presynaptic Function. J Neurochem. 1996;67(5):1974-81. PubMed PMID: 8863503.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nicotinic autoreceptors mediating enhancement of acetylcholine release become operative in conditions of "impaired" cholinergic presynaptic function. AU - Marchi,M, AU - Raiteri,M, PY - 1996/11/1/pubmed PY - 1996/11/1/medline PY - 1996/11/1/entrez SP - 1974 EP - 81 JF - Journal of neurochemistry JO - J Neurochem VL - 67 IS - 5 N2 - The existence in the mammalian CNS of release-inhibiting muscarinic autoreceptors is well established. In contrast, few reports have focused on nicotinic autoreceptors mediating enhancement of acetylcholine (ACh) release. Moreover, it is unclear under what conditions the function of one type of autoreceptor prevails over that of the other. Rat cerebrocortex slices, prelabeled with [3H]choline, were stimulated electrically at 3 or 0.1 Hz. The release of [3H]ACh evoked at both frequencies was inhibited by oxotremorine, a muscarinic receptor agonist, and stimulated by atropine, a muscarinic antagonist. Nicotine, ineffective at 3 Hz, enhanced [3H]ACh release at 0.1 Hz; mecamylamine, a nicotinic antagonist, had no effect at 3 Hz but inhibited [3H]ACh release at 0.1 Hz. The cholinesterase inhibitor neostigmine decreased [3H]ACh release at 3 Hz but not at 0.1 Hz; in the presence of atropine, neostigmine potentiated [3H]ACh release, an effect blocked by mecamylamine. In synaptosomes depolarized with 15 mM KCl, ACh inhibited [3H]ACh release; this inhibition was reversed to an enhancement when the external [Ca2+] was lowered. The same occurred when, at 1.2 mM Ca2+, external [K+] was decreased. Oxotremorine still inhibited [3H]ACh release at 0.1 mM Ca2+. When muscarinic receptors were inactivated with atropine, the K+ (15 mM)-evoked release of [3H]ACh (at 0.1 mM Ca2+) was potently enhanced by ACh acting at nicotinic receptors (EC50 approximately 0.6 microM). In conclusion, synaptic ACh concentration does not seem to determine whether muscarinic or nicotinic autoreceptors are activated. Although muscarinic autoreceptors prevail under normal conditions, nicotinic autoreceptors appear to become responsive to endogenous ACh and to exogenous nicotinic agents under conditions mimicking impairment of ACh release. Our data may explain in part the reported efficacy of cholinesterase inhibitors (and nicotinic agonists) in Alzheimer's disease. SN - 0022-3042 UR - https://www.unboundmedicine.com/medline/citation/8863503/Nicotinic_autoreceptors_mediating_enhancement_of_acetylcholine_release_become_operative_in_conditions_of_"impaired"_cholinergic_presynaptic_function_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0022-3042&date=1996&volume=67&issue=5&spage=1974 DB - PRIME DP - Unbound Medicine ER -