Functional serotonin 5-HT1D receptors and 5-HT1D? receptor mRNA expression in human umbilical vein endothelial cells

Abstract

Pharmacological evidence has suggested the presence of 5-hydroxytryptamine (5-HT, serotonin), 5-HT1D 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-HT1D receptors coupled to inhibition of cyclic AMP formation. 5-HT and the 5-HTlo receptor agonists 5-carboxamidotryptamine (5-CT) and sumatriptan were approximately equipotent at inhibiting forskolin-stimulated cyclic AMP accumulation in HUVEC (mean pECs0 7.6-8.2, maximal effect 30% inhibition). The 5-HTIA receptor agonist, 8-OH-DPAT was clearly less potent (pECs0 6.2) and less efficacious. The selective 5-HT~D receptor antagonist, GR127935 (1 riM) markedly inhibited the effect of 5-HT (apparent pKB 10.8). Reverse transeription-polymerase chain reaction analysis showed the mRNA for 5-HTID~ receptors to be expressed in HU-VEC. These results demonstrate the presence of functional 5-HTID receptors and the expression of 5-HTID~ receptor mRNA in HUVEC. They support the involvement of 5-HT~D~ receptors in endothelial-mediated responses to 5-HT.

Influence of the endothelium and nitric oxide on the contractile responses evoked by 5‐HT1D receptor agonists in the rabbit isolated saphenous vein

“…Furthermore, the presence of 5-HTID receptors on endothelial cells has recently been demonstrated (Schoeffter et al, 1995). Our results suggest that the efficacy, but not the potency of 5-HT, 5-CT and Sum in evoking contractile responses of rabbit saphenous vein rings are largely subject to an inhibitory influence of the E and of an EDRF which is probably NO.…”

“…Furthermore, the presence of 5-HTID receptors on endothelial cells has recently been demonstrated (Schoeffter et al, 1995 (Clitherow et al, 1994;Skingle et al, 1994) surmountably antagonized the contractile responses evoked by 5-HT and Sum, again suggesting interaction with a single receptor population. This is corroborated by the Schild analyses which gave slopes near unity (1.04 and 0.93, respectively).…”

Expression of serotonin receptor mRNAs in blood vessels

“…Although 5-HTloB receptors are expressed in these cells, it should be noted, that the pharmacology of this relaxation was similar but not identical to that of the cloned 5-HT~D~ or 5-HT~Dp receptors. Based on experiments performed with the cloned heterologously expressed 5-HT~Dp receptors [27] and with human endothelial cells from the umbilical vein [28], the 5-HT1D~ receptor inhibits cAMP formation. The endothelium dependent relaxation had previously been shown to be sensitive to pertussis toxin [29], which is in agreement with a G~-protein mediated inhibition of adenylate cyclase.…”

Functional characterization and m‐RNA expression of 5‐HT receptors mediating contraction in human umbilical artery

“…Similarly in human basilar and coronary arteries, sumatriptan is less potent than 5‐HT ( Boulanger et al ., 1995 ; Connor et al ., 1989 ; Parsons et al ., 1989 ). However, a very high potency, pEC 50 8.2±0.2, even higher than that of 5‐HT, for sumatriptan is seen in human umbilical vein endothelial cells ( Schoeffter et al ., 1995 ). 5‐nonyloxytryptamine binds at human 5‐HT 1B/1D receptors with about five times higher affinity than sumatriptan, K i =1.2 and 5.5 n M , respectively ( Glennon et al ., 1994 ).…”