Nitric oxide influences the release of histamine and glutamate in the rat hypothalamus

Abstract

To investigate the influence of nitric oxide (NO) on the release of histamine and glutamate, the anterior hypothalamus of anaesthetized rats was superfused through a push-pull cannula either with artificial cerebrospinal fluid (CSF) or with various drugs dissolved in CSF. Hypothalamic superfusion with the NO-donating compounds linsidomine (200 mumol/l) or diethylamine-NO (DEANO, 100 mumol/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-NG-nitro-L-arginine methyl ester (L-NAME, 200 mumol/l) increased the histamine release rate. The inhibitory effect of 200 mumol/l linsidomine was abolished by atropine (10 mumol/l). Superfusion with the glutamate receptor agonists glutamate (100 mumol/l) or N-methyl-D-aspartate (NMDA, 50 mumol/l) enhanced the histamine release rate. In the presence of linsidomine, the releasing effect of NMDA was not 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 acetylcholine from vicinal cholinergic neurons via stimulation of muscarinic acetylcholine receptors located presynaptically on histaminergic neurons. The NO-induced glutamate release seems to exert a subordinate stimulatory effect on histamine release. Finally, the inhibition of histamine release by NO is not due to blockade of NMDA receptors.

Nitric oxide‐induced increase of excitatory amino acid levels in the trigeminal nucleus caudalis of the rat with tactile hypersensitivity evoked by the loose‐ligation of the inferior alveolar nerves

“…Thus, NO increases formation of the VAMP (also known as synaptobrevin)/SNAP-25/syntaxin 1a core complex and inhibits the binding of n-sec to syntaxin 1a; the combined effects of these activities are linked to promote vesicle docking/ fusion that regulates neurotransmitter release and synaptic plasticity (Meffert et al 1996;Cudeiro and Rivadulla 1999). Related to this, several lines of evidence have suggested that NO donors, like linsidomine, SNAP and NO gas, enhance the release of glutamate, while the NOS inhibitors NLA and L-NAME reduce glutamate output (Guevara-Guzman et al 1994;Segieth et al 1995;Ohta et al 1996;Prast et al 1996;Matsuo et al 2001). We also reported that local application of FK409, an NO donor, in the subcutaneous perfusate in the rat hind instep caused a remarkable increase in SP release from the peripheral endings of primary afferent neurons (Yonehara and Yoshimura 1999).…”

Nitric oxide modulates the discharge rate of basal forebrain neurons

“…In the lateral laterodorsal tegmental nucleus, NO stimulated noradrenaline release (Kodama and Koyama 2006). After blocking the M1 muscarine receptors, NO stimulated histamine release in the hypothalamus (Prast et al 1996).…”

Transient changes in the limbic histaminergic system after systemic kainic acid-induced seizures

“…Histamine-and H 1 receptor-mediated activation through the increase in intracellular Ca 2+ can also induce the production of nitric oxide. Nitric oxide in turn can enhance histamine and glutamate release (Kelm et al, 1993;Prast et al, 1996). Protein kinase C, Ca 2+ , nitric oxide and glutamate are mediators of neuronal cell death (reviewed by Zagulska-Szymczak et al, 2001), thus supporting the activating role of H 1 receptors in neuronal damage.…”