Functional endothelin/sarafotoxin receptors in rat heart myocytes: Structure-activity relationships and receptor subtypes

Ronit Galron, Yoel Kloog, Avner Bdolah, Mordechai Sokolovsky*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Functional receptors for the peptides of the endothelin (ET) and sarafotoxin (SRTX) family were characterized in newborn rat heart myocytes using human and rat endothelins (ET-1 and ET-3, respectively), SRTX-b and SRTX-c. Binding studies in intact cells and homogenates revealed significantly higher affinities of ET-1 and SRTX-b than of ET-3 and SRTX-c towards these receptors. This binding profile of ET SRTX peptides points to their interaction with the receptor subtype designated E-Sα. All four peptides induced time- and dose-dependent phosphoinositide hydrolysis with the following rank order of potency: ET-1 > SRTX-b > SRTX-c > ET-3. Thus, ET-3 which possesses an intermediate affinity toward the receptor was the least effective with regard to this response. These results confirm and extend our earlier report that the ET SRTX peptides interact with a newly characterized receptor(s) associated with phosphoinositide metabolism and Ca2+ mobilization. The initiation of inositol phosphate formation is largely independent of extracellular Ca2+, verapamil and nifedipine, indicating that the ET SRTX peptides are not agonists for the voltage-dependent Ca2+-channels.

Original languageEnglish
Pages (from-to)936-943
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume163
Issue number2
DOIs
StatePublished - 15 Sep 1989

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