Kobe Journal of Medical Sciences, 1998

TI: Nitric oxide is produced via 5-HT1B and 5-HT2B receptor activation in human coronary artery endothelial cells.

AU: Ishida-T; Kawashima-S; Hirata-K; Yokoyama-M

AD: Department of Internal Medicine, Kobe University School of Medicine.

SO: Kobe-J-Med-Sci. 1998 Apr; 44(2): 51-63

ISSN: 0023-2513

PY: 1998



AB: The aim of this study is to clarify the serotonin (5-HT) receptor subtypes responsible for 5-HT-induced nitric oxide (NO) production in cultured human coronary artery endothelial cells (HCAECs). Reverse transcription-polymerase chain reactions revealed that HCAECs possessed only 5-HT1B and 5-HT2B receptor mRNAs. 5-HT (0.001-10 mumol/L) induced nitrite production from HCAEC. A selective 5-HT1B/1D agonist sumatriptan (0.01-10 mumol/L) caused nitrite production. A selective 5-HT2 agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI, 0.01-10 mumol/L) also mimicked the effect of 5-HT. The 5-HT-induced nitrite production was completely inhibited by the nonselective 5-HT1/2 antagonist methiothepin (0.1 mumol/L), but not by the 5-HT2A/2C antagonist ketanserin (0.1 mumol/L). Each of these agonists evoked the elevation of intracellular Ca2+ concentration in HCAECs. These findings suggest that 5-HT-induced NO production is mediated by both of 5-HT1B and 5-HT2B receptor activation in HCAECs. Thus, the 5-HT-evoked endothelium-dependent relaxation of human coronary arteries in vivo might be evoked by net effects of the activation of these receptor subtypes.

Published Bimonthly by Kobe University School of Medicine, Kobe, Japan