Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine the organ distribution of production of the three endothelin (ET) isopeptides, we have developed three ribonuclease protection assays specific for the messenger RNAs (mRNAs) of rat ETs 1, 2, and 3.12 organs from adult Sprague-Dawley rats were examined: heart, lung, liver, spleen, kidney, stomach, small intestine, large intestine, testis, muscle, salivary gland, and brain. The mRNA for ET1 was five times more abundant in the lung than in any other organ studied, moderate expression was seen in the large intestine, and lower levels of mRNA were detected in each of the other organs examined. ET2 was expressed at high level in both large and small intestine and at low level in stomach, muscle, and heart, but ET2 mRNA could not be detected elsewhere. ET3 mRNA was found in all organs, particularly in small intestine, lung, kidney, and large intestine. Because of reports suggesting that ETs might be involved in the hypoperfusion and hypofiltration observed in postischemic kidneys, we have also studied levels of mRNA in kidneys that had previously been subjected to 25 or 45 min of clamping of the renal pedicle. At 6 h after 45 min of ischemia, ET1 mRNA increased to a peak of 421 +/- 69% (mean +/- SEM, n = 3) of that in a standard renal RNA preparation. By contrast, ET3 mRNA decreased in the postischemic organ, falling to a value of 19 +/- 2% of standard at the same time point. The effects of ischemia on ET1 and ET3 mRNAs were long-lasting, with elevation of ET1 and depression of ET3 persisting for days. ET2 mRNA remained undetectable throughout. These findings (a) support a role for ET1 in postischemic renal vascular phenomena and (b) demonstrate a situation in which the expression of ET isoforms is clearly subject to differential regulation.
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PMID:Organ distribution of the three rat endothelin messenger RNAs and the effects of ischemia on renal gene expression. 152 10

In humans, three endothelin (ET) isoforms are predicted to exist by analysis of genomic DNA. However, evidence for the presence of all three mature ET peptides and their precursors remains unclear. Our aim was to identify the ET isoforms present in human heart, using radioimmunoassay (RIA) and reverse-phase high-performance liquid chromatography (RP-HPLC). Antisera raised against the ET-1[15-21] terminal sequence were specific for mature ETs, showing no cross-reactivity with their precursor pro-ETs. Antisera raised against the pro-ET-1[31-38] terminal sequence was specific for pro-ET-1, showing no cross-reactivity with other ET peptides. In extracts of human cardiac tissues, the concentrations of immunoreactive (IR) mature ET and pro-ET-1 were found to be as follows: left atrium (n = 3): 282.3 +/- 113.0, 21.9 +/- 11.0, respectively; right atrium (n = 5): 308.3 +/- 95.4, 43.1 +/- 12.8, respectively; left ventricle (n = 6): 218.5 +/- 64.6, 47.9 +/- 11.9, respectively; right ventricle (n = 4): 215.1 +/- 79.8, 53.9 +/- 13.0, respectively (fmol/g wet weight, mean +/- SEM, for total IR mature ET and pro-ET-1, respectively). RP-HPLC showed peaks of immunoreactivity that coeluted with authentic ET-1 in all extracts of human left atria and ventricle tested. In addition, peaks were also present corresponding to ET-2, ET-3, and pro-ET-1. These results suggest that in addition to ET-1 and pro-ET-1, ET-2 and ET-3 are present in the human heart.
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PMID:Characterization of endothelin isoforms in human heart: endothelin-2 demonstrated. 750 60

Animal kidneys are exquisitely sensitive to the effects of endothelin (ET), but little is known of its binding characteristics, isoform prevalence, or receptor subtype distribution in human kidney. We investigated these parameters using high-performance liquid chromatography, radioimmunoassay (RIA), and the recently synthesized ETA and ETB receptor-selective peptide ligands BQ123 (cyclo[D-Asp-L-Pro-D-Val-L-Leu-D-Trp-]) and BQ3020 (Ala11,15-Ac-ET-1[6-21]). Fresh-frozen normal segments of kidneys excised for carcinoma were solid-phase-extracted using Amprep C2 columns, and parallel eluates were oxidized. All were subjected to RIA for ET and pro-ET-1, in triplicate. ET isoforms were characterized by RP-HPLC and subsequent RIA of eluates. Total amounts of immunoreactive ET were 6.9 +/- 3.8 and 4.5 +/- 1.6 pmol/g wet weight in medulla and cortex, respectively. Reverse-phase high performance liquid chromatography showed peaks of immunoreactivity with retention times identical to synthetic ET-1 and metsulphoxide ET-1. ET-2, ET-3, and pro-ET-1 were not detected. Saturation assays using 0.01-8.0 nM 125I-ET-1 or 125I-BQ3020, gave Kd values (mean +/- SEM) of 0.17 +/- 0.04 and 0.36 +/- 0.06 nM, respectively, with Bmax values of 57.7 +/- 15.4 and 30.0 +/- 5.0 fmol/mg protein, respectively. Hill coefficients were 0.86 +/- 0.03 and 0.77 +/- 0.04, but a two-site fit was not preferred. Receptor autoradiography has detected both subtypes, mainly present in medulla, with ETB predominating.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Human kidney: endothelin isoforms detected by HPLC with radioimmunoassay and receptor subtypes detected using ligands BQ123 and BQ3020. 812 Nov 79

Recent studies have shown that the basal release of PRL from anterior pituitary cells is inhibited by endothelin-1 (ET-1) and ET-3. To determine whether ET also regulates the synthesis and release of PRL by decidual cells, we examined the effects of ET on the synthesis and release of PRL from an enriched fraction of human decidual cells prepared by isopycnic centrifugation of enzymatically dispersed term decidual tissue. Exposure of decidual cells to ET-1 (10(-7) M) for 96 h caused a progressive decrease in basal PRL synthesis and release beginning 24 h after exposure with half-maximal inhibition occurring at an ET-1 concentration of 5 x 10(-9) M. Between 72-96 h of culture, ET-1-exposed cells synthesized 37.2 +/- 2.7% (SEM) and released 32.3 +/- 1.3% less PRL than control cells (P < 0.01). ET-1-exposed cells incubated with [35S]methionine between 72-96 h also released less [35S] PRL than control cells. Sarafotoxin S6C, an ETB receptor agonist, also inhibited basal PRL release, whereas BQ-123, an ETA receptor antagonist, had no effect on basal or on ET-1-mediated inhibition of PRL release. ET-1 also markedly inhibited the stimulation of PRL synthesis and release in response to insulin and insulin-like growth factor-1 (IGF-1). Cells exposed to insulin (100 ng/ml) and IGF-1 (50 ng/ml) alone released 61.2 +/- 3.6% and 40.0 +/- 3.8% more PRL, respectively, than control cells between 72-96 h of exposure. However, cells exposed simultaneously to insulin and ET-1 (10(-7) M) released only 17.1 +/- 3.5% more PRL than control cells during the same time period, and cells exposed simultaneously to IGF-1 and ET-1 released only 4.1 +/- 1.8% more PRL than controls during the same time interval (P vs. insulin or IGF-1 alone < 0.001 in each instance). Both basal and insulin- and IGF-1-stimulated PRL release were also inhibited by the ET isotypes ET-2 and ET-3, and by the ET-1 precursor, big ET. Since macrophages and decidual cells synthesize ET, and decidual tissue contains specific receptors for ET, the inhibitory action of ET on basal and stimulated PRL release may result from an autocrine and/or paracrine effect and appears to be mediated through the ETB receptor.
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PMID:Endothelin inhibits basal and stimulated release of prolactin by human decidual cells. 834 96

In the human heart, we have previously shown the predominance of endothelin (ET) ETA receptors, in addition to the presence of ET-1, ET-2, ET-3, and big ET-1. ET-1 is a potent constrictor of isolated epicardial coronary arteries, and this action is mediated via ETA receptors. To determine the source of ET in the heart, our aims were to obtain cell cultures from human left ventricle, identify the cell type, and characterize ET secretion and receptor expression. We explanted human left ventricular tissue. Positive staining with alpha-actin antibodies confirmed the presence of smooth-muscle cells, whereas negative staining for sarcomeric actin and von Willebrand factor indicated an absence of cardiac myocytes and endothelial cells, respectively. Therefore, the cultures were identified as human left ventricular smooth-muscle cells (HLVSMCs). Because blood vessels were not macroscopically visible in the ventricular tissue, the HLVSMCs most likely originated from intramyocardial resistance vessels. The cells secreted immunoreactive mature ET and big ET-1 (102 +/- 29 and 73 +/- 10 pM/24 h, respectively; mean of three individuals +/- SEM). Saturation binding studies showed that [125I]ET-1 bind with high affinity in this preparation (Kd 0.21 +/- 0.06 nM; Bmax 15 +/- 4 fmol/mg protein; mean of three individuals +/- SEM). A competition binding study using the ETA-selective antagonist FR139317 (10 pM-10 microM) revealed the predominance of ETA receptors (Kd 0.33 +/- 0.10 nM, n = 3). We have shown that smooth-muscle cells isolated from human left ventricle secrete immunoreactive mature ET and big ET-1, and express mainly ETA receptors. These cells may provide a useful model for studying the effects of ET in the regulation of vascular tone and of the blood supply in the myocardium.
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PMID:Delineation of endothelin receptors in human left ventricular smooth-muscle cells. 858 13