Comparison of the effects of endothelin-1, -2 and -3 (1-31) on changes in [Ca2+]i in human coronary artery smooth muscle cells.
We have previously found that human chymase selectively cleaves big endothelins (ETs) at the Tyr31-Gly32 bond to produce 31-amino-acid endothelins, ETs (1-31). In the present study, we investigated the effects of ETs (1-31) on changes in intracellular free Ca2+ ([Ca2+]i) in cultured human coronary artery smooth muscle cells (HCASMCs) using confocal laser microscopy. ETs (1-31) increased [Ca2+]i in a concentration-dependent manner. Phosphoramidon did not inhibit the increases in [Ca2+]i caused by ETs (1-31). The [Ca2+]i increases induced by ETs (1-31) were compared to those of ETs (1-21) and big ETs. ET-1 (1-21) was about 10-times more potent than big ET-1 or ET-1 (1-31), whereas big ET-2 was 10-times less potent than ET-2 (1-21) or ET-2 (1-31). ETs (1-31) may induce [Ca2+]i increase through ET(A)-type or ET(A)-type-like receptors. The 10(-12) M ET (1-31)-induced increases in [Ca2+]i were not affected by removal of extracellular Ca2+, but were inhibited by thapsigargin. These results suggested that ET-1, -2 and -3 (1-31) showed similar potencies in increasing [Ca2+]i and mechanisms of ET (1-31)-induced increases in [Ca2+]i may be similar among the three ETs (1-31).
Yoshizumi
M
M
Department of Pharmacology, The University of Tokushima School of Medicine, Japan.
Inui
D
D
Kirima
K
K
Tsuchiya
K
K
Houchi
H
H
Azuma
M
M
Yasuoka
H
H
Kido
H
H
Tamaki
T
T
D001158:Arteries / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016232:Endothelins / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction
D016232:Endothelins; D002118:Calcium