NITRIC-OXIDE INFLUENCES THE RELEASE OF HISTAMINE AND GLUTAMATE IN THERAT HYPOTHALAMUS

To investigate the influence of nitric oxide (NO) on the release of hi stamine and glutamate, the anterior hypothalamus of anaesthetized rats was superfused through a push-pull cannula either with artificial cer ebrospinal fluid (CSF) or with various drugs dissolved in CSF. Hypotha lamic superfusion with the NO-donating compounds linsidomine (200 mu m ol/l) or diethylamine-NO (DEANO, 100 mu mol/l) led to a pronounced and sustained decrease in the histamine release rate, whereas the release rate of glutamate was enhanced. Superfusion with the inhibitor of NO synthase L-N-G-nitro-L-arginine methyl ester (L-NAME, 200 mu mol/l) in creased the histamine release rate. The inhibitory effect of 200 mu mo l/l linsidomine was abolished by atropine (10 mu mol/l). Superfusion w ith the glutamate receptor agonists glutamate (100 mu mol/l) or N-meth yl-D-aspartate (NMDA, 50 mu mol/l) enhanced the histamine release rate . In the presence of linsidomine, the re leasing effect of NMDA was no t changed. These findings demonstrate that the release of histamine in the hypothalamus is diminished by endogenous NO. This effect of NO on histamine release seems to be due to enhanced release of acetylcholin e from vicinal cholinergic neurons via stimulation of muscarinic acety lcholine receptors located presynaptically on histaminergic neurons. T he NO-induced glutamate release seems to exert a subordinate stimulato ry effect on histamine release. Finally, the inhibition of histamine r elease by NO is not due to blockade of NMDA receptors.