Nitric oxide is produced via 5-HT1B and 5-HT2B receptor activation in human coronary artery endothelial cells.
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.
Department of Internal Medicine, Kobe University School of Medicine.
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T
Ishida
S
S
Kawashima
K
K
Hirata
M
M
Yokoyama
D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D009569:Nitric Oxide / Q000096:biosynthesis*; D011985:Receptors, Serotonin / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D009569:Nitric Oxide; D002118:Calcium