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Regulation of Histamine Release and Synthesis in the Brain by Muscarinic Receptors
Author(s) -
GulatMarnay Christiane,
Lafitte Andrée,
Arrang JeanMichel,
Schwartz JeanCharles
Publication year - 1989
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1989.tb10924.x
Subject(s) - oxotremorine , histaminergic , pirenzepine , carbachol , histamine , chemistry , muscarinic acetylcholine receptor , acetylcholine , endocrinology , medicine , muscarinic acetylcholine receptor m1 , muscarinic agonist , muscarinic antagonist , cholinergic , receptor , biology , biochemistry
The cholinergic modulation of histamine release and synthesis was studied in rat brain slices or synaptosomes labeled with l ‐[ 3 H]histidine. Carbachol in increasing concentrations progressively reduced the K + ‐induced [ 3 H]histamine release from cortical slices. Pirenzepine, a preferential M 1 ‐receptor antagonist, reversed the carbachol effect in an apparently competitive manner and with k i values of 1–6 × 10 −8 M. 11‐[{2‐t(Diethylamino)methyl]‐1‐piperidinyl}acetyl] ‐5,11 ‐ dihydro ‐ 6 H ‐pyrido[2,3 ‐ b ][1,4]benzo ‐ diazepine‐6‐one (AF‐DX 116), considered a preferential M 2 ‐receptor antagonist, reversed the carbachol effect with a mean K i of ∼2 × 10 −7 M. Oxotremorine behaved as a partial agonist in the modulation of histamine release. Neostigmine, an acetylcholinesterase inhibitor, inhibited the K + ‐induced release of [ 3 H]histamine from cortical slices, and the effect was largely reversed by pirenzepine, an observation suggesting a modulation by endogenous acetylcholine. The effects of carbachol and pirenzepine were observed with slices of other brain regions known to contain histaminergic nerve terminals or perikarya, as well as with cortical synaptosomes. The two drugs also modified, in opposite directions, [ 3 H]histamine formation in depolarized cortical slices. In vivo oxotremorine inhibited [ 3 H]histamine formation in cerebral cortex, and this effect was reversed by scopolamine. When administered alone, scopolamine failed to enhance significantly the 3 H‐labeled amine formation, a finding suggesting that muscarinic receptors are not activated by endogenous acetylcholine released under basal conditions. It is concluded that muscarinic heteroreceptors, directly located on histaminergic nerve terminals, control release and synthesis of histamine in the brain. These receptors apparently belong to the broad M 1 ‐receptor category and may correspond to a receptor subclass displaying a rather high affinity for AF‐DX 116.