Roles of brain phosphatidylinositol-specific phospholipase C and diacylglycerol lipase in centrally administered histamine-induced adrenomedullary outflow in rats.
Recently, we reported that intracerebroventricularly (i.c.v.) administered histamine evokes the secretion of noradrenaline and adrenaline from adrenal medulla by brain cyclooxygenase-1- and thromboxane A2-mediated mechanisms in rats. These results suggest the involvement of brain arachidonic acid cascade in the histamine-induced activation of the central adrenomedullary outflow. Arachidonic acid is released mainly by phospholipase A2 (PLA2)-dependent pathway or phospholipase C (PLC)/diacylglycerol lipase-dependent pathway. In the present study, histamine (27 nmol/animal, i.c.v.) -induced elevation of plasma noradrenaline and adrenaline was dose-dependently reduced by U-73122 (PLC inhibitor) (10 and 100 nmol/animal, i.c.v.), ET-18-OCH3 (phosphatidylinositol-specific PLC inhibitor) (10 and 30 nmol/animal, i.c.v.) and RHC-80267 (diacylglycerol lipase inhibitor) (1.3 and 2.6 micromol/animal, i.c.v.). However, mepacrine (PLA2 inhibitor) (1.1 and 2.2 micromol/animal, i.c.v.) and D609 (phosphatidylcholine-specific PLC inhibitor) (30, 100 and 300 nmol/animal, i.c.v.) had no effect. These results suggest the involvement of brain phosphatidylinositol-specific PLC and diacylglycerol lipase in the centrally administered histamine-induced activation of the adrenomedullary outflow in rats.
Shimizu
Takahiro
T
Department of Pharmacology, Graduate School of Medicine, Kochi University, Nankoku, Kochi 783-8505, Japan.
Yamaguchi
Naoko
N
Okada
Shoshiro
S
Lu
Lianyi
L
Sasaki
Tsuyoshi
T
Yokotani
Kunihiko
K
D000313:Adrenal Medulla / Q000378:metabolism*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D003512:Cyclohexanones / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004837:Epinephrine / Q000097:blood*; D004963:Estrenes / Q000494:pharmacology; D006632:Histamine / Q000008:administration & dosage / Q000378:metabolism*; D007276:Injections, Intraventricular; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D009636:Norbornanes; D009638:Norepinephrine / Q000097:blood*; D043265:Phosphatidylinositol Diacylglycerol-Lyase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054801:Phosphoinositide Phospholipase C; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism; D054467:Phospholipases A2; D010742:Phospholipid Ethers / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013859:Thiocarbamates; D013871:Thiones / Q000494:pharmacology; D013997:Time Factors
D001952:Bridged-Ring Compounds; D003512:Cyclohexanones; D004791:Enzyme Inhibitors; D004963:Estrenes; D009636:Norbornanes; D010742:Phospholipid Ethers; D011760:Pyrrolidinones; D013859:Thiocarbamates; D013871:Thiones; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C026659:edelfosine; D016718:Arachidonic Acid; C046498:tricyclodecane-9-yl-xanthogenate; D006632:Histamine; C036535:1,6-bis(cyclohexyloximinocarbonyl)hexane; D010741:Phospholipases A; D008071:Lipoprotein Lipase; D054467:Phospholipases A2; D054801:Phosphoinositide Phospholipase C; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D011796:Quinacrine; D009638:Norepinephrine; D004837:Epinephrine