title: Comparison of the effects of endothelin-1, -2 and -3 (1-31) on changes in [Ca2+]i in human coronary artery smooth muscle cells.
abstract: 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).
authors.affiliation: Department of Pharmacology, The University of Tokushima School of Medicine, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yoshizumi
authors.forename: D
authors.initials: D
authors.lastname: Inui
authors.forename: K
authors.initials: K
authors.lastname: Kirima
authors.forename: K
authors.initials: K
authors.lastname: Tsuchiya
authors.forename: H
authors.initials: H
authors.lastname: Houchi
authors.forename: M
authors.initials: M
authors.lastname: Azuma
authors.forename: H
authors.initials: H
authors.lastname: Yasuoka
authors.forename: H
authors.initials: H
authors.lastname: Kido
authors.forename: T
authors.initials: T
authors.lastname: Tamaki
mesh_terms: 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
chemical_list: D016232:Endothelins; D002118:Calcium