Serotonin potentiates high-glucose-induced endothelial injury: the role of serotonin and 5-HT(2A) receptors in promoting thrombosis in diabetes
| Autor: | Hisae Niki, Kumi Yamada, Hitoshi Nagai, Haruto Nakagawa, Masakuni Nishikawa |
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| Rok vydání: | 2012 |
| Předmět: |
Male
medicine.medical_specialty Serotonin Platelet Aggregation medicine.drug_class Phosphodiesterase 3 Tetrazoles Vascular Cell Adhesion Molecule-1 Sarpogrelate Umbilical vein Diabetes Mellitus Experimental Rats Sprague-Dawley chemistry.chemical_compound Fibrinolytic Agents Diabetes mellitus Internal medicine medicine Human Umbilical Vein Endothelial Cells Animals Humans Receptor Serotonin 5-HT2A Receptor Cells Cultured Pharmacology Aspirin business.industry lcsh:RM1-950 Succinates Thrombosis Receptor antagonist medicine.disease Cilostazol Rats lcsh:Therapeutics. Pharmacology Endocrinology Glucose chemistry cardiovascular system Serotonin 5-HT2 Receptor Antagonists Molecular Medicine business Fibrinolytic agent medicine.drug |
| Zdroj: | Journal of Pharmacological Sciences, Vol 119, Iss 3, Pp 243-250 (2012) |
| ISSN: | 1347-8648 |
| Popis: | To clarify the involvement of 5-hydroxytryptamine (5-HT) in promotion of thrombogenesis in diabetes, we examined the inhibitory effect of sarpogrelate, a 5-HT2A receptor antagonist, on thrombus formation in diabetic rats. In streptozotocin-induced diabetic rats, polyethylene tube–induced thrombus formation was enhanced compared with that in normal rats. The thrombogenesis was inhibited by sarpogrelate; cilostazol, a PDE3 inhibitor; and aspirin, a COX inhibitor, by 75.8%, 42.3%, and 34.3%, respectively. The inhibition by sarpogrelate was more pronounced in diabetic rats than normal ones. High glucose and 5-HT increased the expression of vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs) and combination of both high glucose and 5-HT further potentiated the effect. Sarpogrelate but not aspirin inhibited the increase in VCAM-1 expression induced by high glucose and 5-HT. These findings suggest that 5-HT mediates the enhanced thrombogenesis in diabetes and suggests that a 5-HT2A receptor antagonist may have novel therapeutic potential for the treatment of diabetic complications. Keywords:: 5-hydroxytryptamine, 5-HT2A receptor, human umbilical vein endothelial cell (HUVEC), vascular cell adhesion molecule-1 (VCAM-1), sarpogrelate |
| Databáze: | OpenAIRE |
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