TY - JOUR
T1 - Endothelin-1 induces vasoconstriction through two functionally distinct pathways in porcine coronary artery
T2 - Contribution of phosphoinositide turnover
AU - Kasuya, Yoshitoshi
AU - Takuwa, Yoh
AU - Yanagisawa, Masashi
AU - Kimura, Sadao
AU - Goto, Katsutoshi
AU - Masaki, Tomoh
N1 - Funding Information:
Acknowledgments: We thank Ms. Lisa G. Bond for reading the manuscript. This work was supported in part by grants from the University of Tsukuba Project Research and the Ministries of Education, Science and Culture of Japan.
PY - 1989/6/30
Y1 - 1989/6/30
N2 - Endothelin-1 (ET1)-induced contraction of isolated porcine coronary artery strips was previously reported to be mainly dependent on extracellular Ca2+. However, even in a Ca2+-free, EGTA-containing solution relatively high concentrations of ET1 induced a weak vasoconstriction, which was markedly but not completely inhibited by pretreatment with caffeine. Over similar dose ranges, ET1 stimulated the production of inositol phosphates in a dose-dependent manner in intact arterial tissues, which was independent of extracellular Ca2+ and was not affected by receptor blockers such as atropine, methysergide and diphenhydramine. Moreover, ET1 was shown to induce an increase in 1,2-diacylglycerol. These results indicate that the activation of ET1 receptors on porcine coronary artery smooth muscle causes phosphoinositide breakdown, leading to intracellular Ca2+ mobilization and protein kinase C activation. It is suggested that phospholipase C-mediated phosphoinositide breakdown as well as previously reported activation of voltage-dependent Ca2+ channels are involved in the mechanism of ET1-induced vasoconstriction.
AB - Endothelin-1 (ET1)-induced contraction of isolated porcine coronary artery strips was previously reported to be mainly dependent on extracellular Ca2+. However, even in a Ca2+-free, EGTA-containing solution relatively high concentrations of ET1 induced a weak vasoconstriction, which was markedly but not completely inhibited by pretreatment with caffeine. Over similar dose ranges, ET1 stimulated the production of inositol phosphates in a dose-dependent manner in intact arterial tissues, which was independent of extracellular Ca2+ and was not affected by receptor blockers such as atropine, methysergide and diphenhydramine. Moreover, ET1 was shown to induce an increase in 1,2-diacylglycerol. These results indicate that the activation of ET1 receptors on porcine coronary artery smooth muscle causes phosphoinositide breakdown, leading to intracellular Ca2+ mobilization and protein kinase C activation. It is suggested that phospholipase C-mediated phosphoinositide breakdown as well as previously reported activation of voltage-dependent Ca2+ channels are involved in the mechanism of ET1-induced vasoconstriction.
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U2 - 10.1016/0006-291X(89)91349-1
DO - 10.1016/0006-291X(89)91349-1
M3 - Article
C2 - 2545192
AN - SCOPUS:0024334154
SN - 0006-291X
VL - 161
SP - 1049
EP - 1055
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -