5-HT_(2B) receptor-mediated calcium release from ryanodine-sensitive intracellular stores in human pulmonary artery endothelial cells

摘要

1 We have characterized the 5-hydroxytryptamine (5-HT)-induced calcium signalling in endothelial cells from the human pulmonary artery. Using RT-PCR we show, that of all cloned G-protein coupled 5-HT receptors, these cells express only 5-HT_(1Dβ), 5-HT_(2B) and little 5-HT_4 receptor mRNA. 2 In endothelial cells 5-HT inhibits the formation of adenosine 3′:5′-cyclic monophosphate (cyclic AMP) via 5-HT_(1Dβ) receptors but fails to activate phosphoinositide (PI) turnover. However, the latter pathway is strongly activated by histamine. 3 Despite the lack of detectable inositol phosphate (IP) formation in human pulmonary artery endothelial cells, 5-HT (pD_2= 5.82±0.06, n = 6) or the selective 5-HT_2 agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (pD_2 = 5.66±0.03, n = 7) elicited transient calcium signals comparable to those evoked by histamine (pD_2 = 6.44±0.01, n = 7). Since 5-HT_(2A) and 5-HT_(2C) receptor mRNAs are not detectable in pulmonary artery endothelial cells, activation of 5-HT_(2B) receptors is responsible for the transient calcium release. The calcium transients are independent of the inhibition of adenylate cyclase, since DOI does not stimulate 5-HT_(1Dβ) receptors.