PMID- 24657150 OWN - NLM STAT- MEDLINE DCOM- 20150109 LR - 20140519 IS - 1873-7064 (Electronic) IS - 0028-3908 (Linking) VI - 82 DP - 2014 Jul TI - Possible involvement of brain prostaglandin E2 and prostanoid EP3 receptors in prostaglandin E2 glycerol ester-induced activation of central sympathetic outflow in the rat. PG - 19-27 LID - S0028-3908(14)00090-2 [pii] LID - 10.1016/j.neuropharm.2014.03.005 [doi] AB - 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. CI - Copyright (c) 2014 Elsevier Ltd. All rights reserved. FAU - Shimizu, Takahiro AU - Shimizu T AD - Department of Pharmacology, Kochi University School of Medicine, Nankoku, Kochi 783-8505, Japan. Electronic address: shimizu@kochi-u.ac.jp. FAU - Tanaka, Kenjiro AU - Tanaka K AD - Department of Pharmacology, Kochi University School of Medicine, Nankoku, Kochi 783-8505, Japan. FAU - Nakamura, Kumiko AU - Nakamura K AD - Department of Pharmacology, Kochi University School of Medicine, Nankoku, Kochi 783-8505, Japan. FAU - Taniuchi, Keisuke AU - Taniuchi K AD - Department of Pharmacology, Kochi University School of Medicine, Nankoku, Kochi 783-8505, Japan. FAU - Yawata, Toshio AU - Yawata T AD - Department of Neurosurgery, Kochi University School of Medicine, Nankoku, Kochi 783-8505, Japan. FAU - Higashi, Youichirou AU - Higashi Y AD - Department of Neurosurgery, Kochi University School of Medicine, Nankoku, Kochi 783-8505, Japan. FAU - Ueba, Tetsuya AU - Ueba T AD - Department of Neurosurgery, Kochi University School of Medicine, Nankoku, Kochi 783-8505, Japan. FAU - Dimitriadis, Fotios AU - Dimitriadis F AD - B' Urologic Department, Papageorgiou General Hospital, Aristotle University School of Medicine, Thessaloniki, Greece. FAU - Shimizu, Shogo AU - Shimizu S AD - Department of Pharmacology, Kochi University School of Medicine, Nankoku, Kochi 783-8505, Japan. FAU - Yokotani, Kunihiko AU - Yokotani K AD - Department of Pharmacology, Kochi University School of Medicine, Nankoku, Kochi 783-8505, Japan. FAU - Saito, Motoaki AU - Saito M AD - Department of Pharmacology, Kochi University School of Medicine, Nankoku, Kochi 783-8505, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140319 PL - England TA - Neuropharmacology JT - Neuropharmacology JID - 0236217 RN - 0 (Benzodioxoles) RN - 0 (Catecholamines) RN - 0 (Central Nervous System Agents) RN - 0 (Enzyme Inhibitors) RN - 0 (JZL 184) RN - 0 (Piperidines) RN - 0 (Receptors, Prostaglandin E, EP1 Subtype) RN - 0 (Receptors, Prostaglandin E, EP2 Subtype) RN - 0 (Receptors, Prostaglandin E, EP3 Subtype) RN - 0 (Receptors, Prostaglandin E, EP4 Subtype) RN - 0 (prostaglandin E2 glyceryl ester) RN - 501Q5EQ1GM (sulprostone) RN - EC 3.1.1.23 (Monoacylglycerol Lipases) RN - K7Q1JQR04M (Dinoprostone) RN - X4W3ENH1CV (Norepinephrine) RN - YKH834O4BH (Epinephrine) SB - IM MH - Animals MH - Benzodioxoles/pharmacology MH - Blood Pressure/drug effects/*physiology MH - Brain/drug effects/*physiology MH - Catecholamines/*blood MH - Central Nervous System Agents/pharmacology MH - Dinoprostone/*analogs & derivatives/metabolism/pharmacology MH - Dose-Response Relationship, Drug MH - Enzyme Inhibitors/pharmacology MH - Epinephrine/blood MH - Heart Rate/drug effects/*physiology MH - Male MH - Monoacylglycerol Lipases/antagonists & inhibitors/metabolism MH - Norepinephrine/blood MH - Piperidines/pharmacology MH - Rats, Wistar MH - Receptors, Prostaglandin E, EP1 Subtype/agonists/antagonists & inhibitors/metabolism MH - Receptors, Prostaglandin E, EP2 Subtype/antagonists & inhibitors/metabolism MH - Receptors, Prostaglandin E, EP3 Subtype/agonists/antagonists & inhibitors/*metabolism MH - Receptors, Prostaglandin E, EP4 Subtype/antagonists & inhibitors/metabolism OTO - NOTNLM OT - Central sympathetic outflow OT - Monoacylglycerol lipase OT - Prostaglandin E(2) OT - Prostaglandin E(2) glycerol ester OT - Prostanoid EP(3) receptor OT - Sulprostone EDAT- 2014/03/25 06:00 MHDA- 2015/01/13 06:00 CRDT- 2014/03/25 06:00 PHST- 2013/10/21 00:00 [received] PHST- 2014/03/07 00:00 [revised] PHST- 2014/03/11 00:00 [accepted] PHST- 2014/03/25 06:00 [entrez] PHST- 2014/03/25 06:00 [pubmed] PHST- 2015/01/13 06:00 [medline] AID - S0028-3908(14)00090-2 [pii] AID - 10.1016/j.neuropharm.2014.03.005 [doi] PST - ppublish SO - Neuropharmacology. 2014 Jul;82:19-27. doi: 10.1016/j.neuropharm.2014.03.005. Epub 2014 Mar 19.