title: Centrally administered isoproterenol induces sympathetic outflow via brain prostaglandin E2-mediated mechanisms in rats.
abstract: Brain β-adrenoceptor stimulation can induce elevations of plasma levels of noradrenaline. However, there have been no detailed studies related to signaling pathways downstream of β-adrenoceptors responsible for central sympathetic outflow. In the present study, we pharmacologically examined the possibility that centrally administered isoproterenol can induce elevations of plasma noradrenaline levels in a brain prostaglandin-dependent manner. In addition, we also examined whether or not intracerebroventricular administration of isoproterenol could release endogenously synthesized prostaglandin (PG) E2 in the hypothalamic paraventricular nucleus (PVN) by using the brain microdialysis technique combined with liquid chromatography-ion trap tandem mass spectrometry (LC-ITMS(n)). Under urethane anesthesia, a femoral venous line was inserted for infusion of saline and a femoral arterial line was inserted for collecting blood samples. Next, animals were placed in a stereotaxic apparatus for application of test agents. Catecholamines in the plasma were extracted by alumina absorption and were assayed by high-performance liquid chromatography with electrochemical detection. Quantification of PGE2 in rat PVN microdialysates was performed by the LC-ITMS(n) method. We demonstrated that centrally administered isoproterenol-induced elevations of plasma noradrenaline could be mediated via activation of β-adrenoceptors and the downstream phospholipase A2-cyclooxygenase pathway. Furthermore, PGE2 in the PVN and the PGE2 receptor EP3 subtype appear to play an important role in the process. Our results suggest that central isoproterenol-induced sympathetic outflow is mediated via brain PGE2 in a PGE2 receptor EP3 subtype-dependent manner.
authors.affiliation: Department of Anesthesiology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Ando
authors.affiliation: Department of Pharmacology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Kondo
authors.affiliation: Department of Pharmacology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Yamaguchi
authors.affiliation: Department of Pharmacology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Tachi
authors.affiliation: Advanced Medical Research Center, Aichi Medical University, Nagakute, Aichi, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Fukayama
authors.affiliation: Advanced Medical Research Center, Aichi Medical University, Nagakute, Aichi, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yoshikawa
authors.affiliation: Advanced Medical Research Center, Aichi Medical University, Nagakute, Aichi, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Gosho
authors.affiliation: Department of Anesthesiology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fujiwara
authors.affiliation: Department of Pharmacology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan. Electronic address: okadas@aichi-med-u.ac.jp.
authors.forename: Shoshiro
authors.initials: S
authors.lastname: Okada
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001337:Autonomic Agents / Q000008:administration & dosage*; D002851:Chromatography, High Pressure Liquid; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism*; D007545:Isoproterenol / Q000008:administration & dosage*; D008297:Male; D017551:Microdialysis; D009638:Norepinephrine / Q000097:blood; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000378:metabolism*; D064801:Phospholipase A2 Inhibitors / Q000494:pharmacology; D054467:Phospholipases A2 / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D058308:Receptors, Prostaglandin E, EP3 Subtype / Q000037:antagonists & inhibitors / Q000378:metabolism; D053719:Tandem Mass Spectrometry
chemical_list: D000319:Adrenergic beta-Antagonists; D001337:Autonomic Agents; D016861:Cyclooxygenase Inhibitors; D064801:Phospholipase A2 Inhibitors; D011943:Receptors, Adrenergic, beta; D058308:Receptors, Prostaglandin E, EP3 Subtype; D011451:Prostaglandin-Endoperoxide Synthases; D054467:Phospholipases A2; D015232:Dinoprostone; D007545:Isoproterenol; D009638:Norepinephrine
keywords: Hypothalamic paraventricular nucleus; Plasma noradrenaline; Prostaglandin E(2); β-Adrenoceptor