Cannabinoid and lipid-mediated vasorelaxation in retinal microvasculature
| Autor: | Jiequan Zhu, Dao-Yi Yu, Alex X. Dong, Melanie E. M. Kelly, Eileen M. Denovan-Wright, Susan E. Howlett, Alex Straiker, Amina M. Bagher, Jessica N. MacIntyre |
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| Rok vydání: | 2013 |
| Předmět: |
Male
medicine.medical_specialty Cannabinoid receptor Endothelium medicine.medical_treatment Glycine Arachidonic Acids Biology Retina Receptors G-Protein-Coupled chemistry.chemical_compound Abnormal cannabidiol Internal medicine medicine Cannabinoid receptor type 2 Animals RNA Messenger Receptors Cannabinoid Pharmacology Endothelin-1 Cannabinoids Retinal Vessels Retinal Resorcinols Endocannabinoid system Lipids Rats Inbred F344 Frontal Lobe Vasodilation Endocrinology medicine.anatomical_structure chemistry Microvessels GPR18 Cannabinoid |
| Zdroj: | European journal of pharmacology. 735 |
| ISSN: | 1879-0712 |
| Popis: | The endocannabinoid system plays a role in regulation of vasoactivity in the peripheral vasculature; however, little is known about its role in regulation of the CNS microvasculature. This study investigated the pharmacology of cannabinoids and cannabimimetic lipids in the retinal microvasculature, a CNS vascular bed that is autoregulated. Vessel diameter (edge detector) and calcium transients (fura-2) were recorded from segments of retinal microvasculature isolated from adult, male Fischer 344 rats. Results showed that abnormal cannabidiol (Abn-CBD), an agonist at the putative endothelial cannabinoid receptor, CBe, inhibited endothelin 1 (ET-1) induced vasoconstriction in retinal arterioles. These actions of Abn-CBD were independent of CB1/CB2 receptors and were not mediated by agonists for GPR55 or affected by nitric oxide synthase (NOS) inhibition. However, the vasorelaxant effects of Abn-CBD were abolished when the endothelium was removed and were inhibited by the small Ca(2+)-sensitive K channel (SKCa) blocker, apamin. The effects of the endogenous endocannabinoid metabolite, N-arachidonyl glycine (NAGly), a putative agonist for GPR18, were virtually identical to those of Abn-CBD. GPR18 mRNA and protein were present in the retina, and immunohistochemistry demonstrated that GPR18 was localized to the endothelium of retinal vessels. These findings demonstrate that Abn-CBD and NAGly inhibit ET-1 induced vasoconstriction in retinal arterioles by an endothelium-dependent signaling mechanism that involves SKCa channels. The endothelial localization of GPR18 suggests that GPR18 could contribute to cannabinoid and lipid-mediated retinal vasoactivity. |
| Databáze: | OpenAIRE |
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