CDB15:0000461 EDN1 — EDNRB
Experimentally validated in Human, Mixed species; Orthology-inferred in Human, Mouse, Rat, Frog, Zebrafish, Chicken, Macaque, Pig, Dog, Cow, Chimp, Horse, Marmoset, Sheep
Title
Journal:; Year Published:
Abstract
Lysosomal traffic of liganded endothelin B receptor.
Biochimica et biophysica acta, 2003; PubMed, Homo sapiens EDN1 — Homo sapiens EDNRB
ABSTRACT: The endothelin B receptor (ETB) is an endothelial cell receptor found in caveolae. Studies with GFP-tagged ETB have suggested that the protein is constitutively endocytosed and targeted to lysosomes where it is rapidly degraded. We report that iodinated endothelin-1 ligand (ET-1) is taken up by cells transfected with ETB and remains undegraded for at least 17 h. Analysis of the intracellular traffic of endocytosed ET-1 on isotonic Ficoll gradients shows that it is rapidly internalised to lysosomes by a chloroquine sensitive and cholesterol dependent pathway. Low-temperature nonreducing SDS gels show that the ET-1 initially binds to full-length GFP-tagged ETB, which is rapidly clipped at the amino-terminus and is then stable for at least 6 h. Analysis of GFP tagged ETB on reducing SDS gels shows that it is proteolytically cleaved with a half time of approximately 3 h. However, nonreducing gels show that the receptor is virtually intact, suffering only a similar cleavage to the liganded receptor. We conclude that the ETB receptor shows remarkable stability in lysosomes, held together by disulfide bonds, and maintaining ligand binding for long periods of time.
Cloning and functional expression of human cDNA for the ETB endothelin receptor.
Biochemical and biophysical research communications, 1991; PubMed, Sus scrofa EDN1 — Homo sapiens EDNRB
ABSTRACT: We report the cloning of human cDNA encoding an ETB (non-isopeptide-selective) subtype of the endothelin receptor. The predicted amino acid sequence of the human ETB endothelin receptor was 87.8% and 62.9% identical with the previously cloned rat ETB and ETA receptors, respectively. COS cells transiently transfected with the cloned cDNA expressed specific, high-affinity binding sites for endothelin isopeptides and responded to the peptides with a transient increase of [Ca2+]i; endothelin-1 and endothelin-3 exhibited approximately equal potencies both in displacing 125I-labeled endothelin-1 binding and in eliciting [Ca2+]i transients. The ETB receptor mRNAs were expressed in various human tissues and also in the intact porcine aortic intimal cells ex vivo.
Cloning of a cDNA encoding a non-isopeptide-selective subtype of the endothelin receptor.
Nature, 1990; PubMed, Sus scrofa EDN1 — Rattus norvegicus Ednrb
ABSTRACT: Endothelin-1 was initially identified as a 21-residue potent vasoconstrictor peptide produced by vascular endothelial cells, but was subsequently found to have many effects on both vascular and non-vascular tissues. The discovery of three isopeptides of the endothelin family, ET-1, ET-2 and ET-3, each possessing a diverse set of pharmacological activities of different potency, suggested the existence of several different endothelin receptor subtypes. Endothelins may elicit biological responses by various signal-transduction mechanisms, including the G protein-coupled activation of phospholipase C and the activation of voltage-dependent Ca2+ channels. Thus, different subtypes of the endothelin receptor may use different signal-transduction mechanisms. Here we report the cloning of a complementary DNA encoding one subtype belonging to the superfamily of G protein-coupled receptors. COS-7 cells transfected with the cDNA express specific and high-affinity binding sites for endothelins, responding to binding by the production of inositol phosphates and a transient increase in the concentration of intracellular free Ca2+. The three endothelin isopeptides are roughly equipotent in displacing 125I-labelled ET-1 binding and causing Ca2+ mobilization. A messenger RNA corresponding to the cDNA is detected in many rat tissues including the brain, kidney and lung but not in vascular smooth muscle cells. These results indicate that this cDNA encodes a 'nonselective' subtype of the receptor which is different from the vascular smooth muscle receptor.
Endothelin receptor density in human hypertrophic and non-hypertrophic prostate tissue.
The Tohoku journal of experimental medicine, 1994; PubMed, Homo sapiens EDN1 — Homo sapiens EDNRB
ABSTRACT: The amount of endothelin receptors in human prostate tissue was measured by radioligand binding techniques using 125I-Endothelin -1 and -3 (125I-ET-1, -3). Specimens of the non-hypertrophy group were obtained from 6 patients who underwent total cystectomy under the diagnosis of bladder cancer and those of the hypertrophy group from 6 prostatic hypertrophy patients who underwent open prostatectomy. 125I-ET-1 bound to the prostate tissue with the KD value of 0.033 +/- 0.012 nM in the non-hypertrophy group and with the KD value of 0.035 +/- 0.012 nM in the hypertrophy group. 125I-ET-3 bound to the prostate tissue with the KD value of 0.023 +/- 0.011 nM in the non-hypertrophy group and with the KD value of 0.029 +/- 0.016 nM in the hypertrophy group. The KD values were not significantly different between the hypertrophy and non-hypertrophy groups. The KD values of 125I-ET-1 and 125I-ET-3 were similar. The Bmax values (fmol/mg protein) of 125I-ET-1 binding to the prostate tissue were 32.18 +/- 3.69 to the non-hypertrophy group and 85.66 +/- 20.65 to the hypertrophy group. The Bmax values (fmol/mg protein) of 125I-ET-3 binding to the prostate tissue were 27.48 +/- 5.25 to the non-hypertrophy group and 75.90 +/- 13.46 to the hypertrophy group. The Bmax values of both 125I-ET-1 and 125I-ET-3 were significantly higher in the hypertrophy group than in the non-hypertrophy group.(ABSTRACT TRUNCATED AT 250 WORDS)