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 Ca(2+)-sensitive channels and its effect on basal histamine release in the cerebral cortex of freely-moving unanesthetized rats was investigated. Basal histamine release in the cerebral cortex was determined by in vivo microdialysis coupled with high-performance liquid chromatography (HPLC) fluorometry detection. Basal levels of histamine were 0.67+/-0.02 pmol/10 microl of dialysate. Diltiazem, a Ca(2+) channel antagonist, produced a dose-dependent decrease in dialysate basal histamine concentration. Elevated K(+) (100 mM) in the perfusion medium increased basal histamine to a maximum of 223% of the baseline value. Similarly, diltiazem (60 mM) reduced the K(+), veratridine (100 microg/ml) and ouabain (100 microM)-evoked increase in dialysate histamine. Basal histamine decreased by 48% when the perfusate contained 3 microM of voltage dependent Na(+) antagonist tetrodotoxin. The results of these studies indicate that the release of histamine in rat cerebral cortex can be induced by modulating Na(+) and Ca(2+) channels and that the L-type voltage-dependent sensitive Ca(2+) channels are involved in this release process.
Washington
B
B
Biomedical Research Center, Tennessee State University, Nashville, TN 37209, USA. bwashington@picard.tnstate.edu
Shaw
J B
JB
Li
J
J
Fisher
B
B
Gwathmey
J
J
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000502:physiology; D004110:Diltiazem / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects* / Q000502:physiology; D008297:Male; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000187:drug effects* / Q000502:physiology; D014701:Veratridine / Q000494:pharmacology
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D004791:Enzyme Inhibitors; D015222:Sodium Channels; D010042:Ouabain; D014701:Veratridine; D004110:Diltiazem