Indomethacin とprazosinはLipopolysaccride負荷によるラット視床下部nitric oxide合成酵素含有ニューロンのFos蛋白発現を抑制する

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Lipopolysaccride (LPS) induces the production and release of inflammatory mediators, and elicits the activity of hypothalamus-pituitary-adrenal (HPA) axis. The activation of HPA axis can be potentiated by central PGs and NE released from adrenergic terminals projected from the brain stem, and inhibited by central nitric oxide (NO). The potential interaction between PGs, NE and the one NO is not clear. In order to explore the potential role of PGs and NE in the activities of neurons containing NOS, we investigated the effect of indomethacin and prazosin on the activation of neurons containing NOS induced by LPS with the method of combined Fos immunohistochemistry stain with NADPH stain (the marker of NOS). Our results showed that the NADPH positive neurons are mainly restricted in the PVN and SON. LPS (i.v) significantly induced the Fos expression in the NADPH positive neurons in the nucleus while little Fos expression can be detected in the NADPH positive neurons in the vehicle-treated animals. Pretreatment of indomethacin (i.v), or prazosin (i.v) dramatically suppressed the Fos expression in the NADPH positive neurons challenged by LPS. Our results suggest that in the inflammatory stress, central excitatory neurotransmitters of HPA axis, PGs and NE, can effectively mediate the activation of neurons containing NOS in the PVN and SON. Furthermore, NE can exert its effect on activation of the neurons containing NOS through the α-adrenoceptor. [Jpn J Physiol 54 Suppl:S248 (2004)]