title: Functional endothelin/sarafotoxin receptors in rat heart myocytes: structure-activity relationships and receptor subtypes.
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-S alpha. All four peptides induced time- and dose-dependent phosphoinositide hydrolysis with the following rank order of potency: ET-1 greater than SRTX-b greater than SRTX-c greater than 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.
authors.affiliation: Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, Israel.
authors.forename: R
authors.initials: R
authors.lastname: Galron
authors.forename: Y
authors.initials: Y
authors.lastname: Kloog
authors.forename: A
authors.initials: A
authors.lastname: Bdolah
authors.forename: M
authors.initials: M
authors.lastname: Sokolovsky
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D016232:Endothelins; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D051381:Rats; D011956:Receptors, Cell Surface / Q000302:isolation & purification* / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000302:isolation & purification*; D017466:Receptors, Endothelin; D018000:Receptors, Peptide; D013329:Structure-Activity Relationship; D014757:Viper Venoms / Q000378:metabolism*
chemical_list: D016232:Endothelins; D010455:Peptides; D011956:Receptors, Cell Surface; D011950:Receptors, Cholinergic; D017466:Receptors, Endothelin; D018000:Receptors, Peptide; D014757:Viper Venoms; C058085:sarafotoxin receptor; C057354:sarafotoxins s6; D002118:Calcium