Glutamatergic regulation of histamine release from rat hypothalamus

A microdialysis method was used to study the effects of glutamate on the in vivo release of histamine from the anterior hypothalamic area of rats anesthetized with urethane. Infusion of 1 mM glutamate through a microdialysis probe increased histamine release to about 150% of the basal release. Infusion of N-methyl-D-aspartate (NMDA, 0.1 mM) caused a similar increase. Glutamate-evoked histamine release was completely blocked by D-(-)-2-amino-5-phosphonopentanoic acid (AP5, 0.1 mM), a specific antagonist of NMDA receptors. AP5 alone also reduced histamine release to about 60% of the basal level. Infusion of tetrodotoxin (100 nM) reduced histamine release to about 30% of the basal release, but had no effect on glutamate-evoked release. These results clearly indicate that glutamate enhances histamine release through NMDA receptors located on histaminergic nerve terminals, and suggest that there is a tonic glutamatergic regulation of this release.