Gaseous Neurotransmitter Modulation of Vasopressin and Oxytocin Release
Following microbial invasion, inflammatory mediators are released which bring about vascular and many other changes. In previous studies we have demonstrated that neurohypophysial hormone release can be stimulated by cytokines, particularly interleukin-1 and interleukin-61. This has suggested that inflammatory modulators can directly regulate vasopressin and oxytocin, and vasopressin may in turn have circulatory effects as well as possibly modulating the hypothalamo-pituitary adrenal (HPA) axis. More recently we have begun exploring the role of gaseous neurotransmitters in the hypothalamus in terms of the regulatory control of these two hormones. Specifically we have demonstrated that the synthetic enzyme for nitric oxide, NOS, is present within the hypothalamus, particularly in the supraoptic and paraventricular nuclei2. Donors of nitric oxide (NO) are able to inhibit the stimulated release of vasopressin from acute hypothalamic explants3, while the inducible isoform of NOS can be induced in vivo in rats in response to endotoxin.4,5. Carbon monoxide (CO) is another possible gaseous neuromodulator and is formed from haeme under the influence of heme oxygenase (HO), biliverdin and bilirubin being formed. Carbon monoxide has now been shown to inhibit the stimulated release of the neurohypophjysial hormones in vitro6,7, but by contrast the synthetic enzyme HO is not induced in response to endotoxin. Recent studies have demonstrated that explants acutely exposed to endotoxin show inhibition of vasopressin release, which reverses to stimulation in the presence of an HO inhibitor such as zinc protoporphyrin-IX or tin mesoporphyrin-IX; no marked effect was shown in the presence of NOS antagonists.
KeywordsNitric Oxide Heme Oxygenase Vasopressin Release Oxytocin Release Inflammatory Modulator
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