S-adenosyl-l-methionine inhibits phosphoinositide metabolism in the rat brain synaptosomal suspensions.
S-adenosyl-l-methionine (AdoMet) has been reported to affect events linked to noradrenergic neurotransmission. In the present work, we studied the effect of AdoMet on norepinephrine (NE)-stimulated inositol phosphate production in 3H-inositol-labelled crude synaptosomal suspensions of rat brain. AdoMet (50-1000 microM) decreased both the synthesis of labelled polyphosphoinositide (30-50%) and the release of inositol mono- and bisphosphate (40-50%). The AdoMet effect was not dependent on NE concentration (10-1000 microM), suggesting that the inhibition of inositol phosphate release was not the result of a modification of the norepinephrine binding to its receptor sites. S-adenosyl-L-homocysteine (AdoHcy) (1 mM) an inhibitor of methyltransferase activities, partially inhibited (70%) the AdoMet (0.1 mM) effect, indicating that the methylation processes cannot explain all the effects observed. We conclude that, in addition to previously reported effects of AdoMet on NE transport, AdoMet may reduce NE-linked intracellular signalling.
Fonlupt
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P
INSERM-U205, Laboratoire de Chimie Biologique, Villeurbanne, France.
Bénistant
C
C
Rey
C
C
Lagarde
M
M
D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D007700:Kinetics; D008745:Methylation; D009638:Norepinephrine / Q000502:physiology; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012436:S-Adenosylmethionine / Q000494:pharmacology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D012436:S-Adenosylmethionine; D000242:Cyclic AMP; D009638:Norepinephrine