S-ADENOSYL-L-METHIONINE INHIBITS PHOSPHOINOSITIDE METABOLISM IN THE RAT-BRAIN SYNAPTOSOMAL SUSPENSIONS

S-adenosyl-1-methionine (AdoMet) has been reported to affect events li nked to noradrenergic neurotransmission. In the present work, we studi ed the effect of AdoMet on norepinephrine (NE)-stimulated inositol pho sphate production in H-3-inositol-labelled crude synaptosomal suspensi ons of rat brain. AdoMet (50-1000 muM) decreased both the synthesis of labelled polyphosphoinositide (30-50%) and the release of inositol mo no- and bisphosphate (40-50%). The AdoMet effect was not dependent on NE concentration (10-1000 muM), suggesting that the inhibition of inos itol phosphate release was not the result of a modification of the nor epinephrine 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 methy lation processes cannot explain all the effects observed. We conclude that, in addition to previously reported effects of AdoMet on NE trans port, AdoMet may reduce NE-linked intracellular signalling.