Functional coupling of ETA receptor with Ca(2+)-permeable nonselective cation channel in mouse fibroblasts and rabbit aortic smooth-muscle cells.
Endothelin-1 (ET-1) induces persistent vasoconstriction via a sustained increase in intracellular free Ca2+ concentrations ([Ca2+]i). The mechanisms of the elevation of [Ca2+]i operating at physiologically low concentrations of ET-1 are controversial. Here we report that both native ETA receptors in vascular smooth-muscle cells and recombinant ET(A) receptors expressed in mouse fibroblasts (Ltk cells) are functionally coupled with a non-selective cation channel, which is permeable to Ca2+ and is blocked by mefenamic acid. The channel is persistently activated by a low concentration of ET-1 (10(-10) M) without stimulation of inositol triphosphate (IP3) formation and mediates sustained vasoconstriction.
Enoki
T
T
Department of Pharmacology, Faculty of Medicine, Kyoto University, Japan.
Miwa
S
S
Sakamoto
A
A
Minowa
T
T
Komuro
T
T
Kobayashi
S
S
Ninomiya
H
H
Masaki
T
T
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D016232:Endothelins / Q000494:pharmacology*; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D007473:Ion Channels / Q000187:drug effects* / Q000502:physiology; D008528:Mefenamic Acid / Q000494:pharmacology; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D011817:Rabbits; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin / Q000502:physiology*
D016232:Endothelins; D007473:Ion Channels; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin; D008528:Mefenamic Acid; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium