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 unamiguously on this type of cells. We now report that human umbilical vein endothelial cells (HUVEC) express 5-HT1D receptors coupled to inhibitiion of cyclic AMP formatin. 5-HT and the 5-HT1D receptor agaonists 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-HT1A receptor agonist, 8-OH-DPAT was clearly less potent (pEC50 6.2) and less efficacious. The selective 5-HT1D receptor antagonist, GR127935 (1 nM) markedly inhibited the effct pf 5-HT (apparent pKB 10.8). Reverse transcription-polymerase chain reaction analysis showed the mRNA for 5-HT1Dβ receptors to be expressed in HUVEC. These results demonstrate the presence of functional 5-HT1D receptors and the expression of 5-HT1Dβreceptor mRNA in HUVEC. They support he involvement of 5-HT1Dβ receptors in endothelial-mediated responses to 5-HT.
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References
Adham N, Kao H-T, Schechter LE, Bard J, Olsen M, Urquhart D, Durkin M, Hartig PR, Weinshank RL, Branchek TA (1993) Cloning of another human serotonin receptor (5-HT1F): a fifth 5-HT1 receptor subtype coupled to the inhibition of adenylate cyclase. Proc Natl Acad Sci USA 90:408–412
Aguzzi A (1990) Rapid RNA extraction from tissue and cultured cells. In: Ausubel FM, Brent R, Kingston RE, Moore DD, Seidman JG, Smith JA, Struhl K (eds) Current protocols in molecular biology, the red book bulletin, vol 1 [Suppl 9]. Wiley Interscience, New York, p 1
Clitherow JW, Scopes DIC, Skingle M, Jordan CC, Feniuk W, Campbell IB, Carter MC, Collington EW, Connor HE, Higgins GA, Beattie D, Kelly HA, Mitchell WL, Oxford AW, Wadsworth AH, Tyers MB (1994) Evolution of a novel series of [(N,N-dimethylamino)propyl]-and piperazinylbenzanilides as the first selective 5-HT1D antagonists. J Med Chem 37:2253–2257
Cocks TM, Angus JA (1983) Endothelium-dependent relaxation of coronary arteries by noradrenaline and serotonin. Nature 305:627–630
Flavahan NA, Shimokawa H, Vanhoutte PM (1989) Pertussis toxin inhibits endothelium-dependent relaxations to certain agonists in porcine coronary arteries. J Physiol (Lond) 408:549–560
Gupta P (1992) An endothelial 5-HT receptor that mediates relaxation in guinea-pig isolated jugular vein resembles the 5-HTID subtype. Br J Pharmacol 106:703–709
Hamel E, Fan E, Linville D, Ting V, Villemure J-G, Chia L-S (1993) Expression of mRNA for the serotonin 5-hydroxytryptamine1Dβ receptor subtype in human and bovine cerebral arteries. Mol Pharmacol 44:242–246
Hartig PR, Branchek TA, Weinshank RL (1992) A subfamily of 5-HT1D receptor genes. Trends Pharmacol Sci 13:152–159
McAllister G, Charlesworth A, Snodin C, Beer MS, Noble AJ, Middlemiss DN, Iversen LL, Whiting P (1992) Molecular cloning of a serotonin receptor from human brain (5-HTIE): a fifth 5-HT1-like subtype. Proc Natl Acad Sci USA 89:5517–5521
Martin GR (1994) Vascular receptors for 5-hydroxytryptamine. Pharmacol Ther 62:283–324
Molderings GJ, Engel G, Roth E, Göthert M (1989) Characterization of an endothelial 5-hydroxytryptamine (5-HT) receptor mediating relaxation of the porcine coronary artery. Naunyn-Schmiedeberg's Arch Pharmacol 340:300–308
Schoeffter P, Hoyer D (1989) How selective is GR 43175? Interactions with functional 5-HT1A, 5-HT1B, 5-HT1C and 5-HT1D receptors. Naunyn-Schmiedeberg's Arch Pharmacol 340:135–138
Schoeffter P, Hoyer D (1990) 5-Hydroxytryptamine (5-HT)-induced endothelium-dependent relaxation of pig coronary arteries is mediated by 5-HT receptors similar to the 5-HT1D receptor subtype. J Pharmacol Exp Ther 252:387–395
Schoeffter P, Wacber C, Palacios JM, Hoyer D (1988) The 5-hydroxytryptamine 5-HTID receptor subtype is negatively coupled to adenylate cyclase in calf substantia nigra. Naunyn-Schmiedeberg's Arch Pharmacol 337:602–608
Schoeffter P, Pfeilschifter J, Bobimac I (1995) 5-Hydroxytryptamine 5-HTIB receptors inhibiting cyclic AMP accumulation in rat renal mesangial cells. Naunyn-Schmiedeberg's Arch Pharmacol 351:3539
Weinshank RL, Zgombick JM, Macchi MJ, Branchek TA, Hartig PR (1992) Human serotonin 1D receptor is encoded by a subfamily of two distinct genes: 5-HT1Dα and 5-HT1Dβ. Proc Natl Acad Sci USA 89:3630–3634
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Shoeffter, P., Ullmer, C., Gutierrez, M. et al. Functional serotonin 5-HT1D receptors and 5-HT1Dβ receptor mRNA expression in human umbilical vein endothelial cells. Naunyn-Schmiedeberg's Arch Pharmacol 352, 580–582 (1995). https://doi.org/10.1007/BF00169394
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DOI: https://doi.org/10.1007/BF00169394