Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The diverse biological actions of endothelins (ET) appear to be mediated by specific cell-surface receptors. Autoradiography and membrane binding studies have shown abundant ET binding sites in the kidney. However, their expression in specific types of renal cells is unclear. We studied the binding of 125I-labelled endothelin-1 in freshly isolated cell suspensions from canine inner medullary collecting duct. Competition binding experiments revealed the presence of specific high-affinity binding sites: unlabelled ET-1 and ET-2 compared with the radioligand with an IC50 of 135 and 83 pM, respectively, while the IC50 of ET-3 and big ET-1 were 2 and 4 orders of magnitude higher, indicating the presence of ETA-type receptor. Angiotensin II, vasopressin, and atrial natriuretic peptide (ANP) did not compete for ET binding even at a concentration of 10(-6) M. Saturation binding experiments showed a single class of binding sites of high density (Bmax = 56.7 +/- 10.3 fmol/10(6) cells) and high affinity (Kd = 69.8 +/- 10 pM). In contrast, ANP receptors in the same cell preparations appeared as two classes of binding sites with widely different affinity and density. The high-affinity ANP site (Kd = 311 +/- 48 pM) was compatible with ANP-B (guanylate cyclase-coupled) receptor. ET-1 did not compete for this receptor. ET-1 (10(-7) M) did not alter ANP-induced cGMP generation in these cells (3.8-fold increase at 10(-7) M ANP), nor basal levels of cGMP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Specific endothelin binding sites in renal medullary collecting duct cells: lack of interaction with ANP binding and cGMP signalling. 128 83

Endothelins (ET-1, ET-2 and ET-3) are a family of 21 amino acid peptides produced by endothelial cells. They are thought to regulate the local vasomotor tone with endothelium-derived relaxing factors. ETs are the most potent vasoconstrictor substances yet identified and veins and renal vasculature are the most sensitive targets. They reduce cardiac output and have positive inotropic and chronotropic effects. ETs increase the secretion of atrial natriuretic peptide (ANP), aldosterone and catecholamines but reduce renal blood flow and glomerular filtration and they also have mitogenic properties. ETs bind to receptors (ETA and ETB), activate phospholipase C, modulate intracellular Ca2+ concentration and open Ca2+ channels. Vasoactive agents (adrenaline, angiotensin, vasopressin, thrombin, endotoxins) and hypoxia stimulate the release of ET and also ET gene expression. Raised concentrations of plasma ET have been found to occur in several clinical conditions such as hypertension, myocardial infarction, cardiogenic shock, pregnancy induced hypertension, arteriosclerosis, Raynaud's disease, subarachnoid haemorrhage, uraemia, ulcerative colitis, Crohn's disease and surgical operations suggesting that ETs have a role in several patophysiological processes.
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PMID:Endothelin peptides: biological activities, cellular signalling and clinical significance. 138 14

1. The response of the cutaneous microvasculature to intradermal injection of the endothelins (ET-1, ET-2 and ET-3) and the modulatory effect of endogenously produced nitric oxide (NO) have been determined in the rat. 2. Intradermal injection of endothelins (0.1- 10 pmol/site) induced dose-dependent local reductions in blood flow, measured by 133xenon clearance, with the following potency order; ET-1 = ET-2 greater than ET-3. 3. Laser Doppler blood flowmetry established that ET-1 (10 pmol/site) significantly (P less than 0.05) reduced microvascular blood flow for 3 h after injection. Over a wide dose-range, the response to the endothelins did not include any vasodilatation or visible flare. 4. A possible modulatory role of locally-produced NO was investigated by the intradermal injection of the potent inhibitor of NO generation NG-nitro-L-arginine methyl ester (L-NAME). L-NAME (100 nmol/site) injected alone induced a significant decrease in blood flow. The vasoconstriction induced by L-NAME was partially reversed by L-arginine (P less than 0.05) but not observed with NG-nitro-D-arginine methyl ester (D-NAME). 5. L-NAME significantly (P less than 0.05) enhanced the decrease in blood flow induced by submaximal doses of ET-1, ET-2 and ET-3 and vasopressin, although the results do not suggest that any of the vasoconstrictors stimulate NO release. The response to L-NAME was still observed 3.5 h after inducing a prolonged constriction with ET-1 (10 pmol/site).6. These results indicate that locally produced NO maintains a dilator tone in the cutaneous microvasculature of the rat and acts to modulate the effect of vasoconstrictors such as endothelins. Hence, it is suggested that in conditions where endogenous NO release is reduced, vasoconstrictor agents such as the endothelins could induce a dangerous decrease in blood flow possibly leading to ischaemia and tissue necrosis.
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PMID:Responses to endothelins in the rat cutaneous microvasculature: a modulatory role of locally-produced nitric oxide. 150 57

[125I]ET-1 binding to vascular smooth muscle cells showed an apparent single class of high affinity recognition sites with a Kd of 2.12 +/- 0.46 nM and a Bmax of 81.2 +/- 5.2 fmol/10(6) cells. The specific binding was equally and totally displaced by ET-1 and ET-2 whereas ET-3 presented a different pattern. We investigated heterologous regulation of ET-1 binding sites by preincubating the cells with angiotensin II (AII), Arg-vasopressin, bradykinin, enkephalins, serotonin, norepinephrine and carbachol, for 18 h at 37 degrees C. Only AII pretreatment resulted in an important and dose-dependent decrease of ET-1 binding capacity. Sar1-Ile8-AII inhibited the regulatory effect of AII. Furthermore, preexposure of the cells with phorbol-12,13 dibutyrate but not with phorbol-12,13 didecanoate also resulted in a concentration-dependent diminution of ET-1 binding sites. These findings suggest that AII may selectively down-regulate ET-1 binding sites in vascular smooth muscle cells by a mechanism involving protein kinase C.
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PMID:Angiotensin II and phorbol-esters potently down-regulate endothelin (ET-1) binding sites in vascular smooth muscle cells. 255 1

Human cerebromicrovascular endothelial cells (HBEC) in culture express high affinity ETA receptors coupled to phospholipase C activation. Pretreatment of HBEC with 1 microM dexamethasone for 24 h decreased the number of the ET-1 binding sites (Bmax) on HBEC (96 fmol/mg protein vs 57 fmol/mg protein) without changing the binding affinity (KD) (101 pM vs 92 pM) or displacing profile (ET-1 = ET-2 > ET-3 > S6c). Dexamethasone-pretreated HBEC also exhibited a 40% reduction in the maximal ET-1-stimulated inositol triphosphate (IP3) production, whereas half-maximal stimulatory concentration (EC50) was not affected. This effect of dexamethasone was concentration-dependent, and most pronounced after 24 h of pretreatment. The inhibitory effect of dexamethasone on the ET-1-induced IP3 production was abolished by glucocorticoid-receptor antagonist cortexolone. In contrast, vasopressin-mediated IP3 response in HBEC was not changed by dexamethasone. Cyclo-oxygenase inhibitors indomethacin and acetylsalicylic acid did not influence the ET-1-induced IP3 production by HBEC. The down-regulation of ETA receptors in HBEC by dexamethasone, may represent one of the mechanisms involving the described effects of glucocorticoids on cerebromicrovascular function (i.e. changes in blood brain barrier properties, secretion of vasoactive factors, vascular morphogenesis).
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PMID:Dexamethasone down-regulates endothelin receptors in human cerebromicrovascular endothelial cells. 820 59

The effects of endothelin-1 (ET-1) on protein synthesis and phosphoinositide (PI) hydrolysis were investigated in ventricular myocytes isolated by collagenase digestion of adult rat hearts. The maximum stimulation of protein synthesis by ET-1 was about 35% and the EC50 value was about 0.3 nM. The stimulation was exerted at the translational stage since it was insensitive to inhibition by actinomycin D. The maximum stimulation of PI hydrolysis by ET-1 as measured by the formation of [3H]inositol phosphates was about 11-fold and the EC50 value was about 0.7 nM. The ET-1 analogue sarafotoxin-6b stimulated protein synthesis by a maximum of 27% and stimulated PI hydrolysis about 8- to 9-fold. The EC50 values were 1.6 nM and 0.6 nM, respectively. Other endothelins stimulated protein synthesis and PI hydrolysis in the following order of potency: ET-1 approximately ET-2 > ET-3. This order of potency suggests that the stimulation of both protein synthesis and PI hydrolysis is mediated through the ETA receptor. Although both angiotensin II and [Arg]vasopressin stimulated PI hydrolysis significantly, the stimulation was less than 60%, i.e., much less than the stimulation by ET-1 and its analogues. Neither insulin nor substance P stimulated PI hydrolysis. Stimulation of protein synthesis by ET-1 and its analogues correlated strongly with the stimulation of PI hydrolysis and we suggest that the stimulation of protein synthesis may be dependent on the stimulation of PI hydrolysis. We hypothesize that the mechanism may involve a protein kinase C-mediated increase in intracellular pH.
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PMID:Stimulation of adult rat ventricular myocyte protein synthesis and phosphoinositide hydrolysis by the endothelins. 838 85