TY - JOUR
T1 - Functional endothelin/sarafotoxin receptors in rat heart myocytes
T2 - Structure-activity relationships and receptor subtypes
AU - Galron, Ronit
AU - Kloog, Yoel
AU - Bdolah, Avner
AU - Sokolovsky, Mordechai
PY - 1989/9/15
Y1 - 1989/9/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0024441737&partnerID=8YFLogxK
U2 - 10.1016/0006-291X(89)92312-7
DO - 10.1016/0006-291X(89)92312-7
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AN - SCOPUS:0024441737
SN - 0006-291X
VL - 163
SP - 936
EP - 943
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -
