Labelled histamine was taken up into cultured glial cells of chick embryonic brain by a system with high affinity for histamine and diffusion. The active uptake, occurring at low concentrations of the amine, was Na+ dependent and gave an apparent Km of 0.24 μM and a Vmax of 0.31 pmol X mg protein−1 X min−1. The uptake was completely blocked by desmethylimipramine (Ki = 2.5 μM) and partially by the histamine agonists and histamine‐N‐methyltransferase blockers 4‐methylhistamine and 2‐methylhistamine (I30 values obtained were 2 μM and 5 μM). Other psychoactive drugs were either ineffective (imipramine) or they showed moderate inhibitory effects (amitryptyline and cocaine). Ouabain (100 μM) inhibited uptake by ∼50%. Diffusion occurred at high concentrations of the amine, was insensitive to extracellular Na+, and was proportional to histamine concentration up to 1 mM. [3H]‐Histamine, taken up into the cells, was metabolized and/or released. The spontaneous efflux of the radioactivity measured after 10 min of exposure to [3H]‐histamine (when most of it was still unmetabolized), was moderately Ca++ dependent, accelerated by both reduced concentrations of extracellular Na+ and enhanced concentrations of K+ and inhibited by desmethylimipramine. After prolonged (60 min) incubation, histamine metabolites detected in the cells presented 78% of the chromatogram radioactivity and consisted of Nτ‐methylhistamine and Nτ‐methylimidazole acetic acid. These results indicate that at low nM concentrations, histamine is taken up and metabolized by (and released from) glial cells by an Na+‐dependent system, and the intracellular metabolism seems to serve an increased uptake of the amine. Copyright © 1990 Wiley‐Liss, Inc.
