Evaluation of autoreceptor-mediated control of [(3)H]acetylcholine release in rat and human neocortex.

Abstract:

:In order to assess the autoinhibitory control of endogenous acetylcholine (ACh) in rat and human neocortex, slices of these tissues were prelabelled with [(3)H]choline, superfused continuously and stimulated electrically using various frequencies in the presence or absence of drugs. The autoinhibitory feedback control of [(3)H]ACh release was operative - despite the absence of blockers of ACh esterase - at stimulation frequencies >/= 3 Hz in rat and >/= 6 Hz in human neocortex tissue. At these frequencies the muscarinic antagonist atropine (0.1 microM) disinhibited the release of [(3)H]ACh in both species. Estimation of the biophase concentration of ACh near the autoreceptor in the rat neocortex from concentration-response curves of the muscarinic agonist oxotremorine revealed that at 3 Hz about 25% of the autoreceptors were activated by endogenously released ACh. This estimation is consistent with an increase in [(3)H]ACh release to about 120% of control values by complete blockade of autoreceptors with atropine. The observation that in human neocortical tissue presynaptic autoinhibition of [(3)H]ACh release is operative at stimulation frequencies >/= 6 Hz suggests that selective blockade of autoinhibition may also increase ACh release in the cortex of Alzheimer's disease patients, without additional blockade of the enzyme acetylcholinesterase.

journal_name

Exp Brain Res

authors

Albrecht C,Bloss HG,Jackisch R,Feuerstein TJ

doi

10.1007/s002210050858

keywords:

subject

Has Abstract

pub_date

1999-10-01 00:00:00

pages

383-9

issue

3

eissn

0014-4819

issn

1432-1106

pii

91280383.221

journal_volume

128

pub_type

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