Decreased cerebral catabolism of [3H]histamine in vivo after S-adenosylmethionine administration.

Administration of S-adenosyl-L-methionine (SAM) (200 mg/kg) to adult mice significantly elevated its cerebral levels while the steady-state levels of histamine (HA) and S-adenosyl-L-homocysteine remained unaltered. [3H]HA (1 microCi/10 microliters) was injected intraventricularly (i.vt.) 20 sec, 2, 5, 10 or 20 min prior to sacrifice (1 hr after SAM) and brains were analyzed for [3H]HA, [3H]methylhistamine (MeHA) and [3H]methylimidazoleacetic acid. Brains of SAM-treated mice contained more [3H]HA than vehicle-treated controls at 20 sec, 2, 5 and 10 min (22, 35, 52 and 25%, respectively). [3H]MeHA levels were lower than controls at 20 sec, but higher at 2 and 5 min. Fifteen minutes after i.vt. [3H]histidine, brains of SAM-treated mice contained 47% more [3H]HA and 39% more [3H]MeHA (compared to controls) while [3H]histidine and [3H]methylimidazoleacetic acid levels remained unchanged. SAM treatment had no effect on the activity of cerebral histamine-N-methyltransferase, S-adenosyl-L-homocysteine hydrolase and monoamine oxidase type A (substrate 5-hydroxytryptamine) when tested in vitro, while monoamine oxidase B (substrate phenylethylamine) activity was significantly decreased. In vitro, SAM had no effect on monoamine oxidase A or B. The findings demonstrate that, unexpectedly, the rate of catabolism of HA to MeHA is significantly decelerated in brains containing elevated levels of SAM.