RAT AND MOUSE BRAIN HISTAMINE N -METHYLTRANSFERASE: MODULATION BY METHYLATED INDOLEAMINES 1

Abstract

A purification procedure for rat and mouse brain histamine N -methyltransferase (HMT, EC 2.1.1.8) is described which achieves the preparation of 87-fold purified rat brain and 166-fold purified mouse brain enzyme. The purified HMT (MW 29,000) is inhibited by a number of physiologically and pharmacologically active amines, among them several methylated indoleamines, at concentrations above 5 ± 10 -6 M. At concentrations below 1 ± 10 -7 M, most of the methylated indoleamines stimulate HMT , provided histamine is maintained at, or close to, its optimal concentration as an HMT substrate, namely 1 ± 10 -5 M. A study of the nature of the inhibitory process revealed a non-competitive inhibition of HMT by dopamine as against a competitive inhibition of the enzyme by most methylated indoleamines. Increasing the concentration of histamine beyond the optimal value, i.e. to inhibitory levels, resulted in less stimulation. The findings support the notion that MSO elicits the formation in selected brain cells of supranormal amounts of several methylated indoleamines which are able to stimulate HMT (and possibly other methyltransferases, see Salas et al. , 1977), thereby causing the depletion of the cerebral levels of S-adenosyl-L-methionine, reported previously (Schatz & Sellinger, 1975b).