STUDIES ON S‐ADENOSYLHOMOCYSTEINE INHIBITION OF HISTAMINE TRANSMETHYLATION IN BRAIN

Abstract

Abstract— The mechanism of histamine methyltransferase (HMT) inhibition by S ‐adenosylhomocysteine (SAH) has been investigated on a partially purified enzyme from guinea‐pig brain. The kinetic data indicated that this inhibition was competitive with respect to S ‐adenosylmethionine (SAMe) and noncompetitive with respect to histamine. The K t , values (about 5 ± 10 −6 M in both cases) indicated that SAH had a higher affinity than SAHe or histamine for the enzyme. In rats, after administration of a small dose of SAH, methylation of intracisternally injected [ 3 H]histamine was not modified. However, treatment with l ‐DOPA or pyrogallol induced a decrease in [ 3 H]histamine methylation, presumably due to a modification in the SAMe/SAH ratio in the brain. Hence, histamine methylation in brain could be regulated according to the value of this ratio and thus related to methylation of other biogenic amines.