Brain phospholipase C/diacylglycerol lipase are involved in bombesin BB2 receptor-mediated activation of sympatho-adrenomedullary outflow in rats.
Bombesin receptors are mainly divided into two subtypes: BB1 receptor (neuromedin B-preferring receptor) and BB2 receptor [gastrin-releasing peptide (GRP)-preferring receptor]. Previously, we reported that intracerebroventricularly (i.c.v.) administered bombesin elevates plasma noradrenaline and adrenaline by production of brain arachidonic acid in rats. Arachidonic acid is released mainly by phospholipase A2 (PLA2)-dependent pathway or phospholipase C (PLC)/diacylglycerol lipase-dependent pathway. In the present study, bombesin and GRP elevated plasma catecholamines in a dose-dependent manner (1 and 5 nmol/animal, i.c.v.), while neuromedin B (1, 5 and 10 nmol/animal, i.c.v.) had no effect in urethane-anesthetized rats (bombesin=GRP>>neuromedin B). The bombesin (1 nmol/animal, i.c.v.)-induced response was dose-dependently attenuated by [D-Phe6, des-Met14]-bombesin (6-14) ethylamide (bombesin BB2 receptor antagonist) (15.3 and 30.6 nmol/animal, i.c.v.) and also by U-73122 (PLC inhibitor) (10 and 100 nmol/animal, i.c.v.) and RHC-80267 (diacylglycerol lipase inhibitor) (1.3 and 2.6 micromol/animal, i.c.v.). However, D-Nal-cyclo[Cys-Tyr-d-Trp-Orn-Val-Cys]-Nal-NH2 (bombesin BB1 receptor antagonist) (30 and 100 nmol/animal, i.c.v.), mepacrine (PLA2 inhibitor) (1.1 and 2.2 micromol/animal, i.c.v.) and U-73343 (inactive analog of U-73122) (100 nmol/animal, i.c.v.) had no effect. These results suggest the involvement of brain PLC/diacylglycerol lipase in the brain bombesin BB2 receptor-mediated activation of sympatho-adrenomedullary outflow in rats.
Shimizu
Takahiro
T
Department of Neuropharmacology, Program of Neural Integration, Graduate School of Medicine, Kochi University, Nankoku, Kochi 783-8505, Japan.
Okada
Shoshiro
S
Yamaguchi
Naoko
N
Arai
Junichi
J
Wakiguchi
Hiroshi
H
Yokotani
Kunihiko
K
D000313:Adrenal Medulla / Q000378:metabolism*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001839:Bombesin / Q000031:analogs & derivatives / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D003512:Cyclohexanones / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004837:Epinephrine / Q000097:blood; D004963:Estrenes / Q000494:pharmacology; D019886:Gastrin-Releasing Peptide / Q000494:pharmacology; D007276:Injections, Intraventricular; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D015287:Neurokinin B / Q000031:analogs & derivatives* / Q000494:pharmacology; D009638:Norepinephrine / Q000097:blood; D010456:Peptides, Cyclic / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D011760:Pyrrolidinones / Q000494:pharmacology; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018004:Receptors, Bombesin / Q000037:antagonists & inhibitors / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000502:physiology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism*
C092829:BIM 23127; D003512:Cyclohexanones; D004791:Enzyme Inhibitors; D004963:Estrenes; D010456:Peptides, Cyclic; D011760:Pyrrolidinones; D018004:Receptors, Bombesin; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C074854:U 73343; D016718:Arachidonic Acid; D019886:Gastrin-Releasing Peptide; C036535:1,6-bis(cyclohexyloximinocarbonyl)hexane; D015287:Neurokinin B; C038393:neuromedin B; D010741:Phospholipases A; D008071:Lipoprotein Lipase; D054467:Phospholipases A2; D010738:Type C Phospholipases; D011796:Quinacrine; D001839:Bombesin; D009638:Norepinephrine; D004837:Epinephrine