Serotonin 5-HT₁ Receptors Potentiate Histamine and Thrombin Stimulated Prostaglandin Synthesis in Endothelial Cells

Summary

The ability of serotonin 5-HT₁ receptors to increase vascular tone was previously found to be activated by vasoconstrictiors such as hista-mine. 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 F_2α (PGF_2α) or 6-keto-prostaglandin F_1α (6-keto PGF_α1). 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 PGF_2α levels resulting in an increase in the ratio of PGF_2α over 6-keto PGF_1α . 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.

Keywords

Endothelial cells - serotonin - histamine - prostaglandin

• References

• 1 Cambridge D, Whiting MV, Butterfield LJ, Marston C. Vascular 5-HT_1-like receptors mediating vasoconstriction and vasodilatation: their characterization and distribution in the intact canine cardiovascular system. Br J Pharmacol 1995; 114: 961-8.
• 2 Valentin J-P, Bonnafous R, Gareth WJ. Influence of the endothelium and nitric oxide on the contractile responses evoked by 5-HT_1D receptor agonists in the rabbit isolated saphenous vein. Br J Pharmacol 1996; 119: 35-42.
• 3 Schoeffter P, Hoyer D. 5-Hydroxytryptamine (5-HT)-induced endothelium-dependent relaxation of pig coronary arteries is mediated by 5-HT receptors similar to the 5-HT_1D receptor subtype. J Pharmacol Exp Ther 1990; 252: 387-95.
• 4 Glusa E, Roos A. Endothelial 5-HT receptors mediate relaxation of porcine pulmonary arteries in response to ergotamine and dihydroergotamine. Br J Pharmacol 1996; 119: 330-4.
• 5 Shimokawa H, Flavahan NA, Vanhoutte PM. Loss of endothelial pertussis toxin-sensitive G protein function in atherosclerotic porcine coronary arteries. Circulation 1991; 83: 652.
• 6 Whiting MV, Cambridge D. Canine renovascular responses to sumatriptan and 5-carboxamidotryptamine: modulation through endothelial 5-HT₁-like receptors by endogenous nitric oxide. Br J Pharmacol 1995; 114: 969-74.
• 7 Tadipatri S, van Heuven-Nolson D, Feniuk W, Saxena PR. Analysis of the 5-HT receptors mediating contractions in the rabbit isolated renal artery. Br J Pharmacol 1991; 104: 887-94.
• 8 Sahin-Erdemli I, Hoyer D, Stoll A, Seiler MP. Schoeffter. 5-HT₁-like receptors mediate 5-hydroxytryptamine-induced contraction of the Guinea-pig isolated iliac artery. Br J Pharmacol 1991; 102: 386-90.
• 9 Choppin A, O’Connor SE. Pre-contraction with histamine and U46619 unmasks a 5-HT₁-like receptor in rabbit renal artery. Eur J Pharmacol 1993; 231: 469-72.
• 10 Yildiz O, Tuncer M. Amplification of responses to sumatriptan by various agonists in rabbit isolated iliac artery. J Cardiovasc Pharmacol 1995; 25: 508-10.
• 11 MacLennan SJ, Martin GR. Effect of the thromboxane A₂-mimetic U46619 on the 5-HT₁ like and 5-HT₂ receptor-mediated contraction of the rabbit isolated femoral artery. Br J Pharmacol 1992; 107: 418-21.
• 12 Luscher TF, Rubanyi GB, Aarhus LL, Edoute Y, Vanhoutte PM. Serotonin reduces coronary flow in the isolated heart of the spontaneously hypertensive rat. J Hypertension 1986; 4 (Suppl. 05) S148-S150.
• 13 Luscher TF, Vanhoutte PM. Endothelium-dependent responses to platelets and serotonin in spontaneously hypertensive rats. Hypertension 1986; 8 (suppl II) II-55-II-60.
• 14 Luscher TF. The endothelium target and promoter of hypertension?. Hypertension 1990; 15: 482-5.
• 15 Ullmer C, Schmuck K, Kalkman HO, Lubbert H. Expression of serotonin receptor mRNAs in blood vessels. FEBS Lett 1995; 370: 215-21.
• 16 Ullmer C, Boddeke H, Schmuck K, Lubbert H. 5-HT_2B receptor-mediated calcium release from ryanode-sensitive intracellular stores in human pulmonary artery endothelial cells. Br J Pharmacol 1996; 117: 1081-8.
• 17 Weigel G, Griesmacher A, Toma CD, Baecker C, Heinzl H, Muller MM. Endothelial eicosanoid metabolism and signal transduction during exposure to oxygen radicals injury. Thromb Res 1997; 87: 363-75.
• 18 Camacho M, Lopez-Belmonte J, Vila L. Rate of vasoconstrictor prostanoids released by endothelial cells depends on cyclooxygenase-2 expression and prostaglandin I synthase activity. Circ Res 1998; 83: 353-65.
• 19 Jaffe EA, Grulich J, Weksler BB, Hampel G, Watanabe K. Correlation between thrombin-induced prostacyclin production and inositol trisphosphate and cytosolic free calcium levels in cultured human endothelial cells. J Biol Chem 1987; 262: 8557-65.
• 20 Yildiz O, Tuncer M. Comparison of the effect of endothelium on the responses to sumatriptan in rabbit isolated iliac, mesenteric and corotid arteries. Arch Int Pharmacodyn 1994; 328: 200-12.
• 21 Miller VM, Vanhoutte PM. Endothelium-dependent contractions to arachidonic acid are mediated by products of cyclooxygenase. Am J Physiol 1985; 248: H432-7.
• 22 Katusic ZS, Shepherd JT, Vanhoutte PM. Endothelium-dependent contractions to calcium ionophore A23187, arachidonic acid, and acetylcholine in canine basilar arteries. Stroke 1988; 19: 476-9.
• 23 Luscher TF, Boulanger CM, Yang Z, Noll G, and Dohi Y. Interactions between endothelium-derived relaxing and contracting factors in health and cardiovascular disease. Circulation 1993; 87 (suppl V) V36-V44.
• 24 Auch-Schwelk W, Katusic ZS, Vanhoutte PM. Thromboxane A₂ receptor antagonists inhibit endothelium-dependent contractions. Hypertension 1990; 15: 699-703.
• 25 Kato T, Iwama Y, Okumura K, Hashimoto H, Ito T, Satake T. Prostaglandin H₂ may be the endothelium-derived contracting factor released by acetylcholine in the aorta of the rat. Hypertension 1990; 15: 475-81.
• 26 Forman MB, Oates JA, Robertson D, Robertson RM, Roberts LJ, Virmani R. Increased adventital mast cells in a patient with coronary spasms. N Engl J Med 1985; 313: 1138-41.
• 27 Laine P, Kaartinen M, Penttila A, Panula P, Paavonen T, Kovanen PT. Association between myocardial infarction and the mast cells in the adventitia of the infarct-related coronary artery. Circulation 1999; 99: 361-9.
• 28 Kalsner S, Richards R. Coronary arteries of cardiac patients are hyper-reactive and contain stores of amines: A mechanism for coronary spasm. Science 1984; 233: 1435-7.
• 29 Sakata Y, Komamura K, Hirayama A, Nato S, Kitakaze M, Hori M, Kodama K. Elevation of the plasma histamine concentration in the coronary circulation in patients with variant angina. Am J Cardiol 1996; 77: 1121-6.