In vivo histamine release from brain cortex: the effects of modulating cellular and extracellular sodium and calcium channels

The in vivo mechanisms underlying the actions of modulating Na+- and Ca2+-s ensitive channels and its effect on basal histamine release in the cerebral cortex of freely-moving unanesthetized rats was investigated. Basal histam ine release in the cerebral cortex was determined by in vivo microdialysis coupled with high-performance liquid chromatography (HPLC) fluorometry dete ction. Basal levels of histamine were 0.67 +/- 0.02 pmol/10 mul of dialysat e. Diltiazem, a Ca2+ channel antagonist, produced a dose-dependent decrease in dialysate basal histamine concentration. Elevated K+ (100 mM) in the pe rfusion medium increased basal histamine to a maximum of 223% of the baseli ne value. Similarly, diltiazem (60 mM) reduced the K+, veratridine (100 mug /ml) and ouabain (100 muM)-evoked increase in dialysate histamine. Basal hi stamine decreased by 48% when the perfusate contained 3 muM of voltage depe ndent Na+ antagonist tetrodotoxin. The results of these studies indicate th at the release of histamine in rat cerebral cortex can be induced by modula ting Na+. and Ca2+ channels and that the L-type voltage-dependent sensitive Ca2+ channels are involved in this release process. (C) 2000 Elsevier Scie nce B.V. All rights reserved.