Serotonin potentiates high-glucose-induced endothelial injury: the role of serotonin and 5-HT(2A) receptors in promoting thrombosis in diabetes
To clarify the involvement of 5-hydroxytryptamine (5-HT) in promotion of thrombogenesis in diabetes, we examined the inhibitory effect of sarpogrelate, a 5-HT(2A) receptor antagonist, on thrombus formation in diabetic rats. In streptozotocin-induced diabetic rats, polyethylene tube-induced thrombus...
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| Veröffentlicht in: | Journal of pharmacological sciences 2012, Vol.119 (3), p.243-250 |
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| creator | Yamada, Kumi Niki, Hisae Nagai, Hitoshi Nishikawa, Masakuni Nakagawa, Haruto |
| description | To clarify the involvement of 5-hydroxytryptamine (5-HT) in promotion of thrombogenesis in diabetes, we examined the inhibitory effect of sarpogrelate, a 5-HT(2A) 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-HT(2A) receptor antagonist may have novel therapeutic potential for the treatment of diabetic complications. |
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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. 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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-HT(2A) receptor antagonist may have novel therapeutic potential for the treatment of diabetic complications.</description><subject>Animals</subject><subject>Aspirin - pharmacology</subject><subject>Cells, Cultured</subject><subject>Cilostazol</subject><subject>Diabetes Mellitus, Experimental - blood</subject><subject>Diabetes Mellitus, Experimental - metabolism</subject><subject>Diabetes Mellitus, Experimental - pathology</subject><subject>Fibrinolytic Agents - pharmacology</subject><subject>Glucose - metabolism</subject><subject>Human Umbilical Vein Endothelial Cells - drug effects</subject><subject>Human Umbilical Vein Endothelial Cells - metabolism</subject><subject>Humans</subject><subject>Male</subject><subject>Platelet Aggregation - drug effects</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptor, Serotonin, 5-HT2A - metabolism</subject><subject>Serotonin - metabolism</subject><subject>Serotonin - pharmacology</subject><subject>Serotonin 5-HT2 Receptor Antagonists - pharmacology</subject><subject>Succinates - pharmacology</subject><subject>Tetrazoles - pharmacology</subject><subject>Thrombosis - drug therapy</subject><subject>Thrombosis - metabolism</subject><subject>Thrombosis - prevention & control</subject><subject>Vascular Cell Adhesion Molecule-1 - metabolism</subject><issn>1347-8648</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9UMtOwzAQjJAQLYVfQD6WgyU_EsfhVlVAkSpxoPfIidetq8QOtnPoV_DLBFo4zT5mZ1Zzlc0pz0ssRS5n2W2MR0KYJFTcZDPGSlkQKufZ1wcEn7yzDg0-gUtWJYjoYPcHvO_G1kfA1umxBY3AaZ8O0FnVIeuOYzg9oalHwXeAvEHxX0o5jQq82S3Z6hEFaGFIPkT0YxJ875N1--lyKhsf7e9cW9XA5HyXXRvVRbi_4CLbvTzv1hu8fX99W6-2eCiExJwqTVReVcQQVnFuqCRctEZUxhR5U9KGttOaiUJwnutKK8G0US0nTVHmHPgiW55lp38-R4ip7m1soeuUAz_GmhJWilISSSfqw4U6Nj3oegi2V-FU_2XIvwF6dW6K</recordid><startdate>2012</startdate><enddate>2012</enddate><creator>Yamada, Kumi</creator><creator>Niki, Hisae</creator><creator>Nagai, Hitoshi</creator><creator>Nishikawa, Masakuni</creator><creator>Nakagawa, Haruto</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>2012</creationdate><title>Serotonin potentiates high-glucose-induced endothelial injury: the role of serotonin and 5-HT(2A) receptors in promoting thrombosis in diabetes</title><author>Yamada, Kumi ; Niki, Hisae ; Nagai, Hitoshi ; Nishikawa, Masakuni ; Nakagawa, Haruto</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p568-31ad0a4990f02933f18036cf69ff54b71b1ca492656334d9da62dfac30b5743e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>Aspirin - pharmacology</topic><topic>Cells, Cultured</topic><topic>Cilostazol</topic><topic>Diabetes Mellitus, Experimental - blood</topic><topic>Diabetes Mellitus, Experimental - metabolism</topic><topic>Diabetes Mellitus, Experimental - pathology</topic><topic>Fibrinolytic Agents - pharmacology</topic><topic>Glucose - metabolism</topic><topic>Human Umbilical Vein Endothelial Cells - drug effects</topic><topic>Human Umbilical Vein Endothelial Cells - metabolism</topic><topic>Humans</topic><topic>Male</topic><topic>Platelet Aggregation - drug effects</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptor, Serotonin, 5-HT2A - metabolism</topic><topic>Serotonin - metabolism</topic><topic>Serotonin - pharmacology</topic><topic>Serotonin 5-HT2 Receptor Antagonists - pharmacology</topic><topic>Succinates - pharmacology</topic><topic>Tetrazoles - pharmacology</topic><topic>Thrombosis - drug therapy</topic><topic>Thrombosis - metabolism</topic><topic>Thrombosis - prevention & control</topic><topic>Vascular Cell Adhesion Molecule-1 - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yamada, Kumi</creatorcontrib><creatorcontrib>Niki, Hisae</creatorcontrib><creatorcontrib>Nagai, Hitoshi</creatorcontrib><creatorcontrib>Nishikawa, Masakuni</creatorcontrib><creatorcontrib>Nakagawa, Haruto</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of pharmacological sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yamada, Kumi</au><au>Niki, Hisae</au><au>Nagai, Hitoshi</au><au>Nishikawa, Masakuni</au><au>Nakagawa, Haruto</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Serotonin potentiates high-glucose-induced endothelial injury: the role of serotonin and 5-HT(2A) receptors in promoting thrombosis in diabetes</atitle><jtitle>Journal of pharmacological sciences</jtitle><addtitle>J Pharmacol Sci</addtitle><date>2012</date><risdate>2012</risdate><volume>119</volume><issue>3</issue><spage>243</spage><epage>250</epage><pages>243-250</pages><eissn>1347-8648</eissn><abstract>To clarify the involvement of 5-hydroxytryptamine (5-HT) in promotion of thrombogenesis in diabetes, we examined the inhibitory effect of sarpogrelate, a 5-HT(2A) 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-HT(2A) receptor antagonist may have novel therapeutic potential for the treatment of diabetic complications.</abstract><cop>Japan</cop><pmid>22785018</pmid><tpages>8</tpages></addata></record> |
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| subjects | Animals Aspirin - pharmacology Cells, Cultured Cilostazol Diabetes Mellitus, Experimental - blood Diabetes Mellitus, Experimental - metabolism Diabetes Mellitus, Experimental - pathology Fibrinolytic Agents - pharmacology Glucose - metabolism Human Umbilical Vein Endothelial Cells - drug effects Human Umbilical Vein Endothelial Cells - metabolism Humans Male Platelet Aggregation - drug effects Rats Rats, Sprague-Dawley Receptor, Serotonin, 5-HT2A - metabolism Serotonin - metabolism Serotonin - pharmacology Serotonin 5-HT2 Receptor Antagonists - pharmacology Succinates - pharmacology Tetrazoles - pharmacology Thrombosis - drug therapy Thrombosis - metabolism Thrombosis - prevention & control Vascular Cell Adhesion Molecule-1 - metabolism |
| title | Serotonin potentiates high-glucose-induced endothelial injury: the role of serotonin and 5-HT(2A) receptors in promoting thrombosis in diabetes |
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