Possible inhibitory roles of endogenous 2-arachidonoylglycerol during corticotropin-releasing factor-induced activation of central sympatho-adrenomedullary outflow in anesthetized rats
| Autor: | Lianyi Lu, Takahiro Shimizu, Kunihiko Yokotani |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Male
Agonist medicine.medical_specialty Sympathetic Nervous System Cannabinoid receptor Diacylglycerol lipase Corticotropin-Releasing Hormone medicine.drug_class medicine.medical_treatment 2-Arachidonoylglycerol Monoacylglycerol lipase Arachidonic Acids Glycerides chemistry.chemical_compound Catecholamines Piperidines Internal medicine Cannabinoid Receptor Modulators medicine Animals Anesthesia Rats Wistar Corticotropin-releasing factor Cannabinoid Receptor Agonists Pharmacology Dose-Response Relationship Drug biology Chemistry Brain Cannabinoid CB1 receptor Receptor antagonist Endocannabinoid system Monoacylglycerol Lipases Rats Endocrinology Adrenal Medulla biology.protein Pyrazoles lipids (amino acids peptides and proteins) Cannabinoid Sympatho-adrenomedullary outflow Endocannabinoids |
| Zdroj: | European Journal of Pharmacology. 641:54-60 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/j.ejphar.2010.05.007 |
| Popis: | We previously reported that intracerebroventricularly (i.c.v.) administered corticotropin-releasing factor (CRF) (0.5–3.0 nmol/animal) dose-dependently elevates plasma noradrenaline and adrenaline through brain phospholipase C-, diacylglycerol lipase- and prostanoids-mediated mechanisms in rats. Diacylglycerol produced by phospholipase C from phospholipids can be hydrolyzed by diacylglycerol lipase into 2-arachidonoylglycerol, which may be further hydrolyzed by monoacylglycerol lipase into arachidonic acid, a precursor of prostanoids. Recently, 2-arachidonoylglycerol has been recognized as a major brain endocannabinoid, which can modulate synaptic transmission through presynaptic cannabinoid CB 1 receptors. Released 2-arachidonoylglycerol is rapidly deactivated by uptake into cells and enzymatic hydrolysis. In the present study, therefore, we examined (1) the involvement of brain 2-arachidonoylglycerol, (2) the regulatory role of 2-arachidonoylglycerol as a brain endocannabinoid, and (3) the effect of exogenous cannabinoid receptor agonist, on the CRF-induced elevation of plasma noradrenaline and adrenaline using anesthetized rats. The elevation of both catecholamines induced by a submaximal dose of CRF (1.5 nmol/animal, i.c.v.) was reduced by i.c.v. administered MAFP (monoacylglycerol lipase inhibitor) (0.7 and 1.4 µmol/animal), AM 404 (endocannabinoid uptake-inhibitor) (80 and 250 nmol/animal) and ACEA (cannabinoid CB 1 receptor agonist) (0.7 and 1.4 µmol/animal), while AM 251 (cannabinoid CB 1 receptor antagonist) (90 and 180 nmol/animal, i.c.v.) potentiated the response induced by a small dose of CRF (0.5 nmol/animal, i.c.v.). These results suggest a possibility that 2-arachidonoylglycerol is endogenously generated in the brain during CRF-induced activation of central sympatho-adrenomedullary outflow, thereby inhibiting the peptide-induced response by activation of brain cannabinoid CB 1 receptors in anesthetized rats. |
| Databáze: | OpenAIRE |
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