Two endothelin receptor subtypes in porcine arteries.
Endothelin-1 (ET-1) and ET-3 caused constrictions of endothelium-denuded porcine coronary artery strips with different concentration-response curves: a typical sigmoidal curve to ET-1 and a two-phase sigmoidal curve to ET-3. Binding assays using a membrane preparation demonstrated different Bmax values for [125I]ET-1 and [125I]ET-3 binding. In addition, [125I]ET-1 binding was inhibited by ET-1 and ET-3 with different potencies (ET-1 greater than ET-3), while [125I]ET-3 binding was inhibited by both ETs equally. From these results, two distinct ET receptor subtypes were proposed in the artery; site 1 (selective to ET-1) and site 2 (equally sensitive to both ETs). However, only site 1 was identified on cultured arterial smooth muscle cells (VSMCs) by the binding assay, and this was confirmed since only ET-1 (not ET-3) caused a significant increase in the intracellular free Ca2+ concentration. Therefore, it seems likely that vasoconstriction is mediated via the binding of ET-1 to site 1 (VSMCs) and site 2 (non-VSMCs), or the binding of ET-3 to site 2 (non-VSMCs). Furthermore, site 2 was predominant in nonvascular tissues such as lung, kidney, and cerebellum, thereby suggesting that site 1 may exist in limited tissues such as VSMCs.
Ihara
M
M
Biochemistry, Central Research Laboratory, Banyu Pharmaceutical Co., Ltd., Tokyo, Japan.
Saeki
T
T
Funabashi
K
K
Nakamichi
K
K
Yano
M
M
Fukuroda
T
T
Miyaji
M
M
Nishikibe
M
M
Ikemoto
F
F
D000818:Animals; D001011:Aorta / Q000737:chemistry; D001158:Arteries / Q000737:chemistry*; D002118:Calcium / Q000378:metabolism; D003331:Coronary Vessels / Q000737:chemistry; D016232:Endothelins / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008566:Membranes / Q000737:chemistry; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000502:physiology; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000502:physiology; D017466:Receptors, Endothelin; D013552:Swine; D014661:Vasoconstriction / Q000502:physiology
D016232:Endothelins; D011956:Receptors, Cell Surface; D017466:Receptors, Endothelin; D002118:Calcium