Inhibition of rat brain microsomal Na+,K+-ATPase by S-adenosylmethionine

Rat brain microsomes were preincubated with S-adenosylmethionine (SAM), MgCl2, and CaCl2, then reisolated, and the activity of Na+,K+-ATPase determined. SAM inhibited the Na+,K+-ATPase activity compared with microsomes subjected to similar treatment in the absence of SAM. A biphasic inhibitory effect was observed with a 50% decrease at a SAM concentration range of 0.4 microM-3.2 microM and a 70% reduction at a concentration range above 100 microM. Inclusion of either S-adenosylhomocysteine or 3-deazaadenosine in the preincubations prevented the SAM inhibition of Na+,K+-ATPase activity. The inhibition by SAM appeared to be Mg2+- or Ca2+-dependent.