H3 receptor assay in electrically-stimulated superfused slices of rat brain cortex; effects of N alpha-alkylated histamines and impromidine analogues.

The release of the putative neurotransmitter histamine (HA) from rat brain cortex slices is under negative feedback control by an HA autoreceptor. This autoreceptor has been postulated to belong to a new class of HA receptors, H3. To verify this hypothesis we have developed an assay using superfused rat brain cortex slices. The HA transmitter pool is labelled by incubation of the slices with the precursor 3H-histidine; 3H-HA is estimated after separation by column chromatography. Release of HA was found both after K+-induced depolarization and electrical field stimulation. The latter resulted in higher and more reproducible HA release. Electrically induced HA release could be fully inhibited in a concentration dependent way by exogenous HA in the superfusion buffer. N alpha-alkylated histamines also showed agonistic activity. The action of exogenous HA was totally blocked by the potent H2 agonist impromidine and some of its analogues.