Different endothelin receptor affinities in dog tissues.
Endothelin (ET) is a long-lasting potent vasoconstrictor-peptide. Here we report different binding affinities of endothelin-1 (ET-1) to ET-receptors of various dog tissues. Crude microsomal fractions were prepared after homogenisation of dog tissues in 50 mM Tris/HCl, 20 mM MnCl2, 1 mM EDTA, pH 7.4 by differential centrifugation. Aliquots of microsomal fractions (70 micrograms of protein) were incubated at 25 degrees C for 180 min in the presence of 20 pM 125I-ET-1 and various concentrations of cold ET-1. Four different ET-1 receptor binding affinities were found: adrenals, cerebrum, liver, heart, skeletal muscle and stomach microsomal membranes contained high affinity binding sites (Kd 50 - 80 pM, Bmax 60 - 250 fmol/mg). In cerebellum and spleen medium affinity ET-1 receptors (Kd 350 pM, Bmax 880 and 1200 fmol/mg respectively) were present. In comparison lung and kidney microsomes contained a low affinity ET-1 receptor (Kd 800 and 880 pM, Bmax 1600 and 350 fmol/mg). Receptors of even lower affinity were present in heart, intestine and liver microsomes with Kd values of 3 - 6 nM.
Löffler
B M
BM
Pharmaceutical Research Department, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Löhrer
W
W
D000818:Animals; D004285:Dogs; D016232:Endothelins / Q000378:metabolism*; D007457:Iodine Radioisotopes; D009928:Organ Specificity; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017466:Receptors, Endothelin
D016232:Endothelins; D007457:Iodine Radioisotopes; D011956:Receptors, Cell Surface; D017466:Receptors, Endothelin