Functional serotonin 5-HT1D receptors and 5-HT1D beta receptor mRNA expression in human umbilical vein endothelial cells.
Pharmacological evidence has suggested the presence of 5-hydroxytryptamine (5-HT, serotonin), 5-HT(1D) receptors on endothelial cells but these receptors have never been identified unambiguously on this type of cells. We now report that human umbilical vein endothelial cells (HUVEC) express 5-HT(1D) receptors coupled to inhibition of cyclic AMP formation. 5-HT and 5-HT(1D) receptor agonists 5-carboxamidotryptamine (5-CT) and sumatriptan were approximately equipotent at inhibiting forskolin-stimulated cyclic AMP accumulation in HUVEC (mean pEC50 7.6-8.2, maximal effect 30% inhibition). The 5-HT(1A) receptor antagonist, 8-OH-DPAT was clearly less potent (pEC50 6.2) and less efficacious. The selective 5-HT(1D) receptor agonist, GR127935 (1 nM) markedly inhibited the effect of 5-HT (apparent pK(B) 10.8). Reverse transcription-polymerase chain reaction analysis showed the mRNA for 5-HT(1D beta) receptors to be expressed in HUVEC. These results demonstrate the presence of functional 5-HT(1D) receptors and the expression of 5-HT(1D beta) receptor mRNA in HUVEC. They support the involvement of 5-HT(1D beta) receptors in endothelial-mediated responses to 5-HT.
Schoeffter
P
P
Sandoz Pharma Ltd, Basel, Switzerland.
Ullmer
C
C
Gutierrez
M
M
Weitz-Schmidt
G
G
Lübbert
H
H
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000096:biosynthesis* / Q000235:genetics; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D018170:Sumatriptan / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology / Q000378:metabolism
D012333:RNA, Messenger; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D005576:Colforsin; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D018170:Sumatriptan; C047087:5-carboxamidotryptamine; D000242:Cyclic AMP