期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 875, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ejphar.2020.173034
关键词
2-Deoxy-D-glucose; Thromboxane A(2) Adrenergic receptor; Paraventricular hypothalamic nucleus; Plasma catecholamine
资金
- JSPS KAKENHI from the Japan Society for the Promotion of Science (JSPS) [17K09331, 16K09269]
- Grants-in-Aid for Scientific Research [17K09331, 16K09269] Funding Source: KAKEN
Glucoprivation stimulates a rapid sympathetic response to release and/or secrete catecholamines into the bloodstream. However, the central regulatory mechanisms involving adrenoceptors and prostanoids production in the paraventricular hypothalamic nucleus (PVN) that are responsible for the glucoprivation-induced elevation of plasma catecholamines are still unresolved. In this study, we aimed to clarify whether glucoprivation-induced activation of noradrenergic neurons projecting to the PVN can induce alpha- and/or beta-adrenergic receptor activation and prostanoids production in the PVN to elevate plasma catecholamine levels. We examined the effects of alpha-and beta-adrenergic receptor antagonists, a cyclooxygenase inhibitor, a thromboxane A synthase inhibitor, and a PGE(2) subtype EP3 receptor antagonist on intravenously administered 2-deoxy-D-glucose (2-DG)-induced elevation of noradrenaline in the PVN and plasma levels of catecholamine in freely moving rats. In addition, we examined whether intravenously administered 2-DG can increase prostanoids levels in the PVN microdialysates. Intracerebroventricular (I.c.v.) pretreatment with phentolamine (a non-selective alpha-adrenergic receptor antagonist) suppressed the 2-DG-induced increase in the plasma level of adrenaline, whereas i.c.v. pretreatment with propranolol (a non-selective beta-adrenergic receptor antagonist) suppressed the 2-DG-induced elevation of the plasma level of noradrenaline. pretreatment with indomethacin (a cyclooxygenase inhibitor) and furegrelate (a thromboxane synthase inhibitor) attenuated the 2-DG-induced elevations of both noradrenaline and adrenaline levels. Furthermore, 2-DG administration elevated the thromboxane B-2 level, a metabolite of thromboxane A(2) in PVN microdialysates. Our results suggest that glucoprivation-induced activation of alpha- and beta-adrenergic receptor in the brain including the PVN and then thromboxane A(2) production in the PVN, which are essential for the 2-DG-induced elevations of both plasma adrenaline and noradrenaline levels.
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