Autoinhibition of histamine release by H3 receptors in rat brain cortex depends on stimulation frequency.

Rat cortical slices preloaded with [3H]histidine released [3H]histamine upon electrical stimulation or after depolarization with elevated K+ levels. The release was dependent on the presence of Ca2+, suggesting a neurosecretory process. Histamine has been shown to inhibit its own release mediated by an autoreceptor belonging to the H3-receptor subclass. In this study we have investigated the autoinhibition using different electrical field stimulation conditions (1, 10, 20 and 33.3 Hz). Applying electrical stimulation, the inhibition of [3H]histamine release by histamine is decreased when the stimulation frequency is elevated. When stimulated with 1 Hz histamine is able to block [3H]histamine release completely, with a p(EC50) of 8.1 +/- 0.1. At higher frequencies histamine still blocks [3H]histamine release completely, but with a lower p(EC50).