TY - JOUR
T1 - Endotoxin stimulates an endogenous pathway regulating corticotropin- releasing hormone and vasopressin release involving the generation of nitric oxide and carbon monoxide
AU - Kostoglou-Athanassiou, Ifigenia
AU - Costa, Alfredo
AU - Navarra, Pierluigi
AU - Nappi, Giuseppe
AU - Forsling, Mary L.
AU - Grossman, Ashley B.
PY - 1998/6/1
Y1 - 1998/6/1
N2 - Although the administration of endotoxin in vivo activates the neuroendocrine stress axis in the process of crosstalk between the immune and endocrine axes, the direct application of endotoxin to the hypothalamus in vitro does not stimulate the release of the hypothalamic peptides controlling the hypothalamo-pituitary-adrenal (HPA) axis, corticotropin-releasing hormone (CRH) and vasopressin. The hypothesis has therefore been tested that endotoxin may also activate inhibitory pathways, specifically those involving the generation of nitric oxide (NO) and carbon monoxide (CO). Studies were performed on the isolated rat hypothalamus using endotoxin in the presence or absence of inhibitors of heme oxygenase (which generates CO) and nitric oxide synthase, and ferrous hemoglobin. Endotoxin alone decreased both CRH and vasopressin secretion from the hypothalamus. However, when applied together with a nitric oxide synthase inhibitor, the inhibitory effect on CRH was lost. Conversely, co-administration with heme oxygenase inhibitors transformed the inhibition of vasopressin to stimulation, while having no effect on the inhibition of CRH. Ferrous hemoglobin reversed the inhibition of vasopressin, but did not lead to stimulation. It is therefore concluded that endotoxin may stimulate endogenous pathways that lead to the generation of NO, which in turn inhibits CRH. In addition, it generates CO, which modulates the release of vasopressin. These gases are thus potential counter- regulatory controls to the activation of the HPA.
AB - Although the administration of endotoxin in vivo activates the neuroendocrine stress axis in the process of crosstalk between the immune and endocrine axes, the direct application of endotoxin to the hypothalamus in vitro does not stimulate the release of the hypothalamic peptides controlling the hypothalamo-pituitary-adrenal (HPA) axis, corticotropin-releasing hormone (CRH) and vasopressin. The hypothesis has therefore been tested that endotoxin may also activate inhibitory pathways, specifically those involving the generation of nitric oxide (NO) and carbon monoxide (CO). Studies were performed on the isolated rat hypothalamus using endotoxin in the presence or absence of inhibitors of heme oxygenase (which generates CO) and nitric oxide synthase, and ferrous hemoglobin. Endotoxin alone decreased both CRH and vasopressin secretion from the hypothalamus. However, when applied together with a nitric oxide synthase inhibitor, the inhibitory effect on CRH was lost. Conversely, co-administration with heme oxygenase inhibitors transformed the inhibition of vasopressin to stimulation, while having no effect on the inhibition of CRH. Ferrous hemoglobin reversed the inhibition of vasopressin, but did not lead to stimulation. It is therefore concluded that endotoxin may stimulate endogenous pathways that lead to the generation of NO, which in turn inhibits CRH. In addition, it generates CO, which modulates the release of vasopressin. These gases are thus potential counter- regulatory controls to the activation of the HPA.
KW - Carbon monoxide
KW - CRH
KW - Endotoxin
KW - LPS
KW - Nitric oxide
KW - Vasopressin
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U2 - 10.1016/S0165-5728(98)00028-9
DO - 10.1016/S0165-5728(98)00028-9
M3 - Article
C2 - 9655478
AN - SCOPUS:0032101177
VL - 86
SP - 104
EP - 109
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
SN - 0165-5728
IS - 1
ER -