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)

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

Endothelin (ET) receptors are present in pituitary cells and stimulate hormone release through the phosphoinositide/Ca2+ signaling system. In pituitary cell suspensions, ET caused [Ca2+]i elevations of much higher amplitudes than those induced by other vasoactive hormones, including angiotensin II, vasopressin, and noradrenalin. The action of ET was coupled to rapid and transient activation of exocytosis in gonadotrophs, thyrotrophs, somatotrophs, and lactotrophs. In contrast, angiotensin II did not stimulate luteinizing hormone release, and luteinizing hormone responses to vasopressin and noradrenalin were very small. Single gonadotrophs exhibited three types of [Ca2+]i responses to increasing doses of ET, (a) subthreshold responses, with amplitude modulation; (b) threshold-oscillatory responses, with frequency modulation; and (c) threshold-biphasic responses, as the summation of single Ca2+ spikes. The same [Ca2+]i patterns were also seen in gonadotropin-releasing hormone (GnRH)-stimulated cells. In the presence of [Ca2+]e, the amplitudes of the Ca2+ spikes progressively decreased during continuous stimulation with ET or GnRH, reaching the nonoscillatory plateau level after 200-400 sec of stimulation. In cells stimulated with GnRH, subsequent exposure to ET, GnRH, or ionomycin during the plateau phase did not elicit further increases in [Ca2+]i, whereas cells stimulated with ET responded partially to all three agents. In addition, cells exposed to ET or GnRH for 30 min, followed by a 30-min recovery period, were able to mount a full [Ca2+]i response to GnRH, but not to ET-1. Similarly, both peptides elicited rapid increases in LH release, with comparable potencies, but the response to ET decreased much more rapidly during sustained stimulation and gonadotrophs became refractory to further ET stimulation. This is in part attributable to rapid endocytosis of ET receptors during continuous agonist stimulation. These data indicate that ET exerts potent but transient secretory actions in several pituitary cell types and is a potential regulator of gonadotropin release. The initial receptor-coupling events in both ET- and GnRH-stimulated cells are similar, but the differences observed during continuous or repetitive stimulation indicate that the ET receptor pathway undergoes rapid desensitization that is critical in determining the distinct cellular responses to the two peptides.
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PMID:Calcium signaling and secretory responses in endothelin-stimulated anterior pituitary cells. 164 50

In endothelial cells of the blood vessels and in other cell types by the cleavage of precursor-molecules 21 amino acids containing peptides--the endothelins--are formed. There exist 3 isoforms. The synthesis of endothelin 1 in the endothelial cells is stimulated by adrenaline, noradrenaline, angiotensin II, arginine-vasopressin, thrombine, interleukin 1 and hypoxia. Receptors for endothelins are distributed in most tissues. A significance of the endothelins apparently exists in the stimulation of the activity of the heart and in the vasoconstriction in the case of a decrease of the blood pressure (when blood is lost) and of hypoxia. Endothelins are also formed in the lungs, the kidneys, the brain and the eye. In experimental animals already a low dose of endothelin has a lethal effect by inducing disturbances in the cardiovascular system. By the snake species Atractaspis engaddensis formed sarafotoxins have a similar structure as the endothelins and are effective by binding to their receptors.
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PMID:[Endothelins--properties, formation, mechanism of action and significance]. 165 17

By means of intracellular recordings we have studied the actions of the vasoactive peptides endothelin-1 and -3 (ET-1, ET-3) and arginine vasopressin (AVP) on the membrane potential of astrocytes in explant cultures of rat spinal cord and brainstem. Addition of ET-1, ET-3 or AVP to the bathing solution at concentrations of 10(-8)-10(-6) M depolarized the membrane of the majority of glial cells studied. The AVP antagonist d(CH2)5(1), Tyr(Me)2, Arg8-vasopressin reversibly blocked the depolarizations by AVP. Our electrophysiological findings together with autoradiographic binding studies strongly suggest the existence of ET and AVP receptors on astrocytes.
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PMID:Electrophysiological evidence for the existence of receptors for endothelin and vasopressin on cultured astrocytes of rat spinal cord and brainstem. 166 42

Endothelin (ET1) and vasoactive intestinal contractor (VIC) stimulate quiescent Swiss 3T3 cells to resume DNA synthesis acting synergistically with epidermal growth factors (EGF) and other mitogens. The peptide [D-Arg1,D-Phe5,D-Trp7,9,Leu11] substance P has been identified as a broad spectrum neuropeptide antagonist which blocks the binding and biological effects of the Ca2(+)-mobilizing neuropeptides bombesin, vasopressin, and bradykinin. In the present study we show that [D-Arg1,D-Phe5,D-Trp7,9,Leu11] substance P also acts as an ET1/VIC antagonist as judged by the following criteria: a) inhibition of specific 125I-labelled ET1 binding to a ET1/VIC receptor in a competitive and dose-dependent manner; b) blocking of the rapid increase in the cytosolic Ca2+ concentration promoted by ET1 or VIC; and c) inhibition of DNA synthesis stimulated by VIC in the presence of EGF. The inhibitory effects of [D-Arg1,D-Phe5,D-Trp7,9,Leu 11] substance P on Ca2+ mobilization and DNA synthesis were reversed by increasing the concentration of VIC. This is the first time that a peptide structurally unrelated to ET1 or VIC is shown to block the binding and mitogenic effects of peptides of the endothelin family.
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PMID:[D-Arg1,D-Phe5,D-Trp7,9,Leu11]substance P, a neuropeptide antagonist, blocks binding, Ca2(+)-mobilizing, and mitogenic effects of endothelin and vasoactive intestinal contractor in mouse 3T3 cells. 169 96

1. The coronary vasoconstrictive response to endothelin (ET-1) was evaluated using the isolated perfused hearts of 15 week old spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto rats (WKY). Endothelin produced marked increases in perfusion pressure (PP) in both SHR and WKY. The effects of ET-1 were more potent than those of acetylcholine, vasopressin and angiotensin II. The vascular response to ET-1, expressed as the increase in PP, was greater in SHR than in WKY. 2. Nicardipine (10(-8) mol/L) shifted the concentration-PP response curve for ET-1 to the right. The extent of the rightward shift was greater in SHR than in WKY. Additionally in SHR, Bay K-8644 elicited a dose-dependent increase in PP, the effect being more potent than that in WKY. 3. The increased response of the coronary vasculature to ET-1 was observed after 15 weeks of age but not at 6 weeks, indicating that enhancement of the response develops with ageing in SHR. 4. Enhancement of the vascular response to ET-1 in SHR was prevented by chronic (10 weeks) treatment with enalapril (10 mg/kg per day), but not by hydralazine (30 mg/kg per day). 5. These results indicate that the coronary vascular response to ET-1 increases with age in SHR. The mechanism of the enhanced response may involve the activation of dihydropyridine-sensitive Ca2+ channels, however, this type of mechanism may also be modulated at least in part by the renin-angiotensin system.
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PMID:Coronary vascular response to endothelin in isolated perfused hearts of spontaneously hypertensive rats. 151 76

Endothelin (ET) exerts various biological actions in mesangial cells, including stimulation of proliferation, contraction and phospholipase C activation. We investigated the presence of specific ET receptors on cultured rat mesangial cells, incubating the cells in the presence of [125I]ET-1 both at 22 and 4 degrees C. ET binding was time- and temperature-dependent and achieved equilibrium at 2 hr at 22 degrees C and at 5 hr at 4 degrees C. Scatchard analyses of equilibrium saturation curves with [125I]ET-1 and homologous competition curves revealed the presence of a single class of high-affinity binding sites (Kd = 31.4 +/- 7.08 pM). Heterologous competition experiments with ET-3 and sarafotoxin, however, indicated the presence of two binding sites for ET-related peptides in mesangial cells with a Kd for ET-3 of 41.5 +/- 19.2 and of 374 +/- 38.5 nM. Nifedipine and arginine-vasopressin failed to compete for ET binding sites. Preincubation of the cells with 1 nM ET-1 caused a dramatic decrease in ET binding capacity (from 0.5-0.02 fmol/100,000 cells) without affecting the Kd for the receptors (38 pM). ET receptor down regulation was not prevented by protein kinase C inhibition with H-7 and sangiovamycin, or after down regulation of protein kinase C induced by 24-hr preincubation with phorbol myristate acetate. ET receptor down regulation also exerts functional effects, as we found a decrease in intracellular-free calcium response to ET-1 after long-term preincubation with the same agonist. Our results are consistent with the presence of two binding sites for ET in rat mesangial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endothelin binding and receptor down regulation in rat glomerular mesangial cells. 184 3

Endothelin (ET) is a vasoactive peptide produced by both endothelial epithelial cells with documented mitogenic action on mesangial cells. The present studies were designed to test the hypothesis that ET is also produced by human mesangial cells (HMC) and that other mitogens such as arginine vasopressin (AVP) and insulin stimulate cellular proliferation, in part, through modulation of endogenous production of this peptide. Studies were conducted on cultured normal HMC between the third and seventh passages. All mitogenesis experiments were carried out in 96-well plates and assessed by tritiated thymidine incorporation into DNA under various concentrations of AVP in the presence and absence of insulin, antiendothelin antisera (ETAS), a MAb against ET-1 (AbET), and a vasopressin-1 receptor antagonist. ET concentrations were measured daily from conditioned medium by a sensitive and specific RIA. ET was present in all concentrations of FCS as well as conditioned medium compared with medium alone. AVP (10(-6) M) in the presence of insulin increased ET production by quiescent HMC by 261% as well as cellular proliferation by 440% after 48 h incubation. In addition, cells cultured with ETAS or AbET demonstrated a blunted mitogenic response to AVP, a response not observed in cells cultured with ETAS where ET was added. Insulin significantly potentiated the mitogenic effects of AVP as well as media levels of ET, an effect significantly blunted by AbET. We conclude that ET is produced by HMC and its production is affected, in part, by both AVP and insulin. ET may thus serve to modulate the mitogenic effects of AVP on human mesangial cells.
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PMID:Arginine vasopressin stimulates human mesangial cell production of endothelin. 201 May 32

Endothelin (ET), a peptide originally isolated from the supernatants of cultured endothelial cells, exerts a wide variety of biological effects in different tissues. Endothelial-cell-synthesized ET-1 has been proposed to act in a paracrine manner on adjacent smooth muscle cells (SMC) in vivo, with effects that include both vascular reactivity (vasodilation/vasoconstriction) and mitogenesis. This study, by the use of immunocytochemically characterized SMC (rVSMC) isolated from the aortas of spontaneously hypertensive rats, has investigated a possible autocrine role for ET in regulation of the vasculature. Although quiescent cultures of rVSMC apparently did not constitutively express prepro ET-1mRNA, ET-specific transcripts could be induced by a variety of growth factors (transforming growth factor beta [TGF-beta]; platelet-derived growth factor-AA homodimer [PDGF-A chain]) and vasoactive hormones (angiotensin II [Ang II], arginine-vasopressin, and ET-1 itself). The kinetics for prepro ET-1mRNA induction in rVSMC were characteristically rapid in onset and transient. Down-regulation of protein kinase C by 48 h pretreatment of rVSMC with phorbol ester markedly reduced the subsequent ability of rVSMC to express ET-1 transcripts and secrete ET-1 peptide in response to Ang II. Inducible prepro ET-1mRNA expression was accompanied by a cycloheximide-inhibitable release of ET-1 peptide into the medium of rVSMC. ET-1 peptide was determined by both radioreceptor- and radioimmunoassay. Stimulated rVSMC accumulated ET-1 (approximately 200 pg.10(6) cells-1 x 4 h-1) at levels that attained biological relevance (approximately 10(-10) M). Sep-pak C18 extracts of medium from stimulated rVSMC elicited contraction of isolated endothelium-denuded rat mesenteric resistance vessels, and this response was characteristically protracted and difficult to "wash out." Synthetic (porcine) ET-1 promoted the expression of transcripts for PDGF-A chain, TGF-beta, and thrombospondin in quiescent rVSMC. Such effects of ET-1 on gene expression may be relevant to the mitogenic potential of ET-1 on VSMC. Our findings imply a role for ET-1 in the control of vascular function via both paracrine and autocrine regulatory mechanisms. The expression of prepro ET-1mRNA and peptide biosynthesis by rVSMC may have both short-term (e.g., vasoconstriction) and long-term (e.g., structural remodeling) consequences. A sustained loop of autocrine stimulation by ET-1 in SMC could contribute toward the pathogenesis of vasospasm and/or atherosclerosis.
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PMID:Stimulation of endothelin mRNA and secretion in rat vascular smooth muscle cells: a novel autocrine function. 207 71

In vascular smooth muscle cells, the vasoconstrictor peptide, endothelin (ET-1) possesses specific binding sites sensitive to homologous and heterologous regulation. In this study, we have compared the regulation of ET-1 receptors induced by ET-1 and by angiotensin II. After 18 hours preincubation of cultured rat aortic smooth muscle cells at 37 degrees C in presence of vasoactive substances (1 microM) such as norepinephrine, Met- and Leu-enkephalins, bradykinin, serotonin, histamine or carbachol, the binding characteristics of [125I]ET-1 were not modified. On the same conditions, Arg-vasopressin (1 microM) was able to down-regulate ET-1 receptors by less than 30 p. 100 whereas both ET-1 (1 nM) and angiotensin II (10 nM) reduced the number of ET-1 binding sites (Bmax) by more than 50 p. 100 without modification of the affinity (Kd). The time course of the effect of the two peptides showed a rapid decrease of ET-1 binding sites induced by ET-1 and a comparatively slow regulation elicited by angiotensin II. Sar1-Ile8-angiotensin II blocked the effect of angiotensin II. These results show that ET-1 and angiotensin II can regulate ET-1 receptors and suggest a possible modulation of ET-1 activity by endogenous levels of the two peptides.
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PMID:[Homologous and heterologous regulations of endothelin receptors on smooth muscle cells]. 217 81


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