N-sulphation of desipramine in the rat brain

Abstract

1. Amine N-sulphotransferase (NST) activity with desipramine (DMI) as substrate was assayed in vitro in various areas of the rat brain. Biosynthesis of 3'-phosphoadenosine-5'-phospho³⁵sulphate (PAPS) from sodium ³⁵sulphate and ATP was also measured by coupling it to the sulphation of minoxidil by minoxidil sulphotransferase (MST).

2. For the DMI–NST reaction, an apparent K_m = 0.5 mM was obtained for DMI and two apparent K_ms = 0.3 and 1.7 µM for PAPS, whereas in the PAPS-generating reactions, K_m for sodium ³⁵sulphate = 20 µM.

3. Both the enzyme activities were widely distributed in rat brain. The rate of NST activity was 2–3 orders of magnitude lower than that of PAPS generation. N-sulphoconjugation of DMI, which is proposed as a possible biotransformation pathway of DMI in the rat brain, could conceivably be supported adequately by the 'active sulphate' generated within the same areas of the brain.