PMID- 32097659 OWN - NLM STAT- MEDLINE DCOM- 20210107 LR - 20210107 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 875 DP - 2020 May 15 TI - Thromboxane A(2) in the paraventricular hypothalamic nucleus mediates glucoprivation-induced adrenomedullary outflow. PG - 173034 LID - S0014-2999(20)30126-6 [pii] LID - 10.1016/j.ejphar.2020.173034 [doi] AB - 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 EP(3) 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. I.c.v. 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. CI - Copyright (c) 2020 Elsevier B.V. All rights reserved. FAU - Tachi, Masahiko AU - Tachi M AD - Aichi Prefectural Institute of Public Health, Japan. FAU - Yamaguchi, Naoko AU - Yamaguchi N AD - Department of Pharmacology, Aichi Medical University School of Medicine, Japan. FAU - Okada, Shoshiro AU - Okada S AD - Department of Pharmacology, Aichi Medical University School of Medicine, Japan. Electronic address: okadas@aichi-med-u.ac.jp. LA - eng PT - Journal Article DEP - 20200222 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Benzofurans) RN - 0 (Blood Glucose) RN - 0 (Receptors, Adrenergic, alpha) RN - 0 (Receptors, Adrenergic, beta) RN - 57576-52-0 (Thromboxane A2) RN - 9G2MP84A8W (Deoxyglucose) RN - KX4D9BZA6X (furegrelate) RN - X4W3ENH1CV (Norepinephrine) RN - XXE1CET956 (Indomethacin) RN - YKH834O4BH (Epinephrine) RN - Z468598HBV (Phentolamine) SB - IM MH - Adrenal Medulla/*metabolism MH - Animals MH - Benzofurans/administration & dosage MH - Blood Glucose/*metabolism MH - Deoxyglucose/administration & dosage MH - Epinephrine/blood/metabolism MH - Indomethacin/administration & dosage MH - Injections, Intraventricular MH - Male MH - Neurons/metabolism MH - Norepinephrine/blood/metabolism MH - Paraventricular Hypothalamic Nucleus/drug effects/*metabolism MH - Phentolamine/administration & dosage MH - Rats MH - Receptors, Adrenergic, alpha/metabolism MH - Receptors, Adrenergic, beta/metabolism MH - Thromboxane A2/*metabolism OTO - NOTNLM OT - 2-Deoxy-D-glucose OT - Adrenergic receptor OT - Paraventricular hypothalamic nucleus OT - Plasma catecholamine OT - Thromboxane A(2) COIS- Declaration of competing interest None. EDAT- 2020/02/26 06:00 MHDA- 2021/01/08 06:00 CRDT- 2020/02/26 06:00 PHST- 2019/11/25 00:00 [received] PHST- 2020/02/20 00:00 [revised] PHST- 2020/02/21 00:00 [accepted] PHST- 2020/02/26 06:00 [pubmed] PHST- 2021/01/08 06:00 [medline] PHST- 2020/02/26 06:00 [entrez] AID - S0014-2999(20)30126-6 [pii] AID - 10.1016/j.ejphar.2020.173034 [doi] PST - ppublish SO - Eur J Pharmacol. 2020 May 15;875:173034. doi: 10.1016/j.ejphar.2020.173034. Epub 2020 Feb 22.