Serotonin 5-HT1 receptors potentiate histamine and thrombin stimulated prostaglandin synthesis in endothelial cells.
The ability of serotonin 5-HT1 receptors to increase vascular tone was previously found to be activated by vasoconstrictiors such as histamine. In this study, treatment of cultured human aortic endothelial cells (HAEC) with the 5-HT1-selective agonist 5-carboxamidotryptamine (5-CT) alone had no effect on the levels of prostaglandin F2alpha (PGF2alpha) or 6-keto-prostaglandin F1alpha (6-keto PGF1alpha). However, 5-CT potentiated the histamine and thrombin stimulated increases in prostaglandins released by HAEC. In the presence of histamine, increasing doses of 5-CT caused a steep rise in PGF2alpha levels resulting in an increase in the ratio of PGF2alpha over 6-keto PGF1alpha. The ability of 5-CT to potentiate prostaglandin production was correlated with its ability to potentiate the histamine and thrombin mediated mobilization of arachidonic acid. These results demonstrate that the ability of 5-HT1 receptors to stimulate prostaglandin production in endothelial cells is activated by histamine and thrombin.
Kilbourne
E J
EJ
Endocrinology Division, Women's Health Research Institute, Wyeth Ayerst Research, Radnor, PA, USA. kilboune@war.wyeth.com
Winneker
R C
RC
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism; D015237:Dinoprost / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D011453:Prostaglandins / Q000096:biosynthesis* / Q000378:metabolism; D011985:Receptors, Serotonin / Q000502:physiology*; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000031:analogs & derivatives* / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology*
D011453:Prostaglandins; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D016718:Arachidonic Acid; D012701:Serotonin; D015121:6-Ketoprostaglandin F1 alpha; D006632:Histamine; C047087:5-carboxamidotryptamine; D015237:Dinoprost; D013917:Thrombin