title: Possible involvement of brain prostaglandin E2 and prostanoid EP3 receptors in prostaglandin E2 glycerol ester-induced activation of central sympathetic outflow in the rat.
abstract: We recently reported that intracerebroventricularly administered 2-arachidonoylglycerol elevated plasma noradrenaline and adrenaline by brain monoacylglycerol lipase- (MGL) and cyclooxygenase-mediated mechanisms in the rat. These results suggest that 2-arachidonoylglycerol is hydrolyzed by MGL to free arachidonic acid, which is further metabolized to prostaglandins (PGs) by cyclooxygenase in the brain, thereby elevating plasma noradrenaline and adrenaline. On the other hand, 2-arachidonoylglycerol can be also metabolized by cyclooxygenase to PG glycerol esters (PG-Gs), which seems to be hydrolyzed by MGL to free PGs. Here, we examined the involvement of brain PG-Gs in the elevation of plasma noradrenaline and adrenaline regarding PGE2-G and prostanoid EP receptors using anesthetized male Wistar rats. Intracerebroventricularly administered PGE2-G (1.5 and 3 nmol/animal) dose-dependently elevated plasma noradrenaline but not adrenaline. PGE2-G also elevated systolic, mean and diastolic blood pressure and heart rate. The PGE2-G-induced elevation of plasma noradrenaline was attenuated by JZL184 (MGL inhibitor). Intracerebroventricularly administered PGE2 (0.3 and 1.5 nmol/animal) and sulprostone (0.1 and 0.3 nmol/animal) (EP1/EP3 agonist) also elevated plasma noradrenaline but not adrenaline in a dose-dependent manner. The sulprostone-induced elevation was attenuated by L-798,106 (EP3 antagonist), but not by SC-51322 (EP1 antagonist). L-798,106 also attenuated the PGE2-G- and PGE2-induced elevation of plasma noradrenaline, while PF-04418948 (EP2 antagonist) and L-161,982 (EP4 antagonist) had no effect on the PGE2-G-induced response. These results suggest a possibility that brain PGE2-G produced from 2-arachidonoylglycerol can be hydrolyzed to free PGE2, thereby activating central sympathetic outflow by brain prostanoid EP3 receptor-mediated mechanisms in the rat.
authors.affiliation: Department of Pharmacology, Kochi University School of Medicine, Nankoku, Kochi 783-8505, Japan. Electronic address: shimizu@kochi-u.ac.jp.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Department of Pharmacology, Kochi University School of Medicine, Nankoku, Kochi 783-8505, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Department of Pharmacology, Kochi University School of Medicine, Nankoku, Kochi 783-8505, Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Department of Pharmacology, Kochi University School of Medicine, Nankoku, Kochi 783-8505, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Taniuchi
authors.affiliation: Department of Neurosurgery, Kochi University School of Medicine, Nankoku, Kochi 783-8505, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Yawata
authors.affiliation: Department of Neurosurgery, Kochi University School of Medicine, Nankoku, Kochi 783-8505, Japan.
authors.forename: Youichirou
authors.initials: Y
authors.lastname: Higashi
authors.affiliation: Department of Neurosurgery, Kochi University School of Medicine, Nankoku, Kochi 783-8505, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ueba
authors.affiliation: B' Urologic Department, Papageorgiou General Hospital, Aristotle University School of Medicine, Thessaloniki, Greece.
authors.forename: Fotios
authors.initials: F
authors.lastname: Dimitriadis
authors.affiliation: Department of Pharmacology, Kochi University School of Medicine, Nankoku, Kochi 783-8505, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Shimizu
authors.affiliation: Department of Pharmacology, Kochi University School of Medicine, Nankoku, Kochi 783-8505, Japan.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Yokotani
authors.affiliation: Department of Pharmacology, Kochi University School of Medicine, Nankoku, Kochi 783-8505, Japan.
authors.forename: Motoaki
authors.initials: M
authors.lastname: Saito
mesh_terms: D000818:Animals; D052117:Benzodioxoles / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D002395:Catecholamines / Q000097:blood*; D002491:Central Nervous System Agents / Q000494:pharmacology; D015232:Dinoprostone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004837:Epinephrine / Q000097:blood; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008994:Monoacylglycerol Lipases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009638:Norepinephrine / Q000097:blood; D010880:Piperidines / Q000494:pharmacology; D017208:Rats, Wistar; D058306:Receptors, Prostaglandin E, EP1 Subtype / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000037:antagonists & inhibitors / Q000378:metabolism; D058308:Receptors, Prostaglandin E, EP3 Subtype / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D052117:Benzodioxoles; D002395:Catecholamines; D002491:Central Nervous System Agents; D004791:Enzyme Inhibitors; C534333:JZL 184; D010880:Piperidines; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058308:Receptors, Prostaglandin E, EP3 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; C518978:prostaglandin E2 glyceryl ester; C016767:sulprostone; D008994:Monoacylglycerol Lipases; D015232:Dinoprostone; D009638:Norepinephrine; D004837:Epinephrine
keywords: Central sympathetic outflow; Monoacylglycerol lipase; Prostaglandin E(2); Prostaglandin E(2) glycerol ester; Prostanoid EP(3) receptor; Sulprostone