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(Circulation. 1998;97:234-236.)
© 1998 American Heart Association, Inc.

Brief Rapid Communications

Endothelin-1 Inhibits Endothelin-Converting Enzyme-1 Expression in Cultured Rat Pulmonary Endothelial Cells

Shojiro Naomi, MD; Taisuke Iwaoka, MD; Tumba Disashi, MD; Junnosuke Inoue, MD; Yoshie Kanesaka, MD; Hiroshi Tokunaga, MD; ; Kimio Tomita, MD

From the Third Department of Internal Medicine, Kumamoto University School of Medicine, Japan.

Correspondence to Shojiro Naomi, Third Department of Internal Medicine, Kumamoto University School of Medicine, 1–1-1 Honjo, Kumamoto 860, Japan.

Background—The lung expresses large amounts of endothelin-converting enzyme-1 (ECE-1), which catalyzes a step in the biosynthesis of potent vasoactive endothelin-1 (ET-1) from the inactive intermediate big ET-1. Because there has been no report concerning a possible relationship between ET-1 and ECE-1, we investigated the effects of ET-1 on ECE-1 expression in cultured rat pulmonary endothelial cells.

Methods and Results—ECE-1 messenger RNA (mRNA) and protein expression in cultured endothelial cells were assayed by Northern and Western blotting, respectively. Incubation with ET-1 for 6 hours caused a significant decrease in ECE-1 mRNA expression. The action of ET-1 on ECE-1 mRNA expression was antagonized by pretreatment with BQ788, a specific ETB receptor antagonist, but not by pretreatment with BQ123, a specific ETA receptor antagonist. The expression of ECE-1 protein was also inhibited at 6 hours after incubation with ET-1. The effects of ET-1 on ECE-1 mRNA and protein expression were shown to be mimicked by ionomycin, a calcium ionophore, but not by 12-O-tetradecanoylphorbol 13-acetate, a protein kinase C activator.

Conclusions—The present results demonstrate that ET-1 suppressed ECE-1 protein levels by inhibiting ECE-1 mRNA expression through the ETB receptor, suggesting the existence of a feedback action of ET-1 on ECE-1 in pulmonary endothelial cells.

Key Words: endothelin • endothelium • receptors

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