Tele-methylhistamine as an index of the activity of central histaminergic neurons

Abstract

The activity of histaminergic neurons was examined in various brain regions. Histamine (HA) and tele-methylhistamine (t-MH) were simultaneously assayed using HPLC with fluorescence detector. The HA content was high in the hypothalamus and thalamus and low in the cerebellum and pons-medulla oblongata in the rat, mouse and guinea-pig. The t-MH content was high in the hypothalamus and amygdala in all these species, and was exceptionally high in guinea-pig hippocampus. Pargyline hydrochloride (80 mg/kg, i.p.) increased the t-MH content of the rat brain linearly up to 4 hr after injection. The increments of t-MH (Δt-MH) were large in the hypothalamus, striatum and thalamus (108.7, 80.2 and 62.1 ng/g/hr, respectively), but very slight in the cerebellum (2.9 ng/g/hr). Although relatively high HA levels were observed in the spinal cord, no increase in t-MH was detected after pargyline treatment. There was a significant correlation between At-MH and steady-state t-MH levels in different brain regions (r = 0.82, p < 0.01). The treatment with α-fluoromethylhistidine (50 mg/kg, i.p.) produced 15-60 % depletion of HA 4 hr later in various rat brain regions except for the spinal cord. The percentage of depletion was regarded as that of neuronal HA to the total HA. The half-life of neuronal HA estimated from the methyl-ation rate by a one compartment open model was in a range of 7.7-56.6 min in the following rank order: striatum < hippocampus < midbrain < amygdala < cerebral cortex < pons-medulla oblongata < thalamus < hypothalamus. These results indicate that the t-MH levels and the increments after pargyline treatment are useful as indices of the brain histaminergic function.