Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 658, Issue 2-3, Pages 123-131Publisher
ELSEVIER
DOI: 10.1016/j.ejphar.2011.02.023
Keywords
Bombesin; Adrenomedullary outflow; Brain; 2-Arachidonoylglycerol; Monoacylglycerol lipase; Cannabinoid CB1 receptor
Categories
Funding
- Ministry of Education, Culture, Sports, Science and Technology [21790627]
- Japan Society for the Promotion of Science [20590702]
- Smoking Research Foundation in Japan
- Kochi University
- Kochi Medical School Hospital
- Grants-in-Aid for Scientific Research [20590702, 21790627] Funding Source: KAKEN
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We previously reported the involvement of brain diacylglycerol lipase and cyclooxygenase in intracerebroventricularly (i.c.v.) administered bombesin-induced secretion of noradrenaline and adrenaline from the adrenal medulla in rats. Diacylglycerol can be hydrolyzed by diacylglycerol lipase into 2-arachidonoylglycerol, which may be further hydrolyzed by monoacylglycerol lipase into arachidonic acid, a substrate of cyclooxygenase. 2-Arachidonoylglycerol is a major endocannabinoid, which can inhibit synaptic transmission by presynaptic cannabinoid CB, receptors. Released 2-arachidonoylglycerol is rapidly inactivated by uptake into cells and enzymatic hydrolysis. In the present study, we examined the involvement of brain 2-arachidonoylglycerol and its regulatory role in the bombesin-induced central activation of adrenomedullary outflow using anesthetized rats. The elevation of plasma noradrenaline and adrenaline induced by a submaximal dose of bombesin (1 nmol/animal, i.c.v.) was reduced by MAFP (monoacylglycerol lipase inhibitor) (0.28 and 0.7 mu mol/animal, i.c.v.). JZL184 (selective monoacylglycerol lipase inhibitor) (0.7 and 1.4 mu mol/animal, i.c.v.), ACEA (CB, receptor agonist) (0.7 and 1.4 pi-not/animal, i.c.v.) and AM 404 (endocannabinoid uptake-inhibitor) (80 and 250 nmol/animal, i.c.v.), while AM 251 (CBI receptor antagonist) (90 and 180 nmol/animal, i.c.v.) potentiated the response induced by a small dose of bombesin (0.1 nmol/animal, i.c.v.). These results suggest a possibility that 2-arachidonoylglycerol is endogenously generated in the brain during bombesin-induced activation of central adrenomedullary outflow, thereby inhibiting the peptide-induced response by activation of brain CBI receptors in rats. (C) 2011 Elsevier B.V. All rights reserved.
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