Rapid down regulation of Ca2+ signals induced by endothelin-1 in a human bronchial epithelial cell line

Oles, Markus; Ewert, Monika; Meyer, Thomas; Pott, Lutz

doi:10.1016/s0143-4160(97)90046-4

Cited by 9 publications

(9 citation statements)

References 37 publications

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“…1, in line with our previous study (Oles et al 1997), a brief challenge (10-20 s) of a single epithelial cell by 10 nM ET-1 resulted in a Ca 2+ transient which lasted for several minutes. The width at 90% recovery under standard conditions was always >6 min and was independent of the duration of exposure to ET-1.…”

Section: Resultssupporting

confidence: 90%

“…It is also conceivable and not contradictory to this hypothesis that this time window is determined by activity of the Ca 2+ entry mechanism, which contributes to the Ca 2+ transient for several hundred seconds after an exposure to ET-1 of only 10 s in duration as shown previously (Oles et al 1997; see also Fig. 3C).…”

Section: Resultssupporting

confidence: 50%

“…The latter has been demonstrated to reflect a novel type of long-term desensitization. (Oles et al 1997). It should be noted that the term 'desensitization' has not been coined to a distinct mechanism but is normally used as a generic term to refer to any process whereby receptors become refractory or less responsive to a given stimulus (DebBurman and Hosey 1995).…”

Section: Discussionmentioning

confidence: 99%

“…On the cellular level we have shown previously that a single exposure of airway epithelial cells for as short as 10-20 s caused a reduction or a complete loss of sensitivity to a subsequent exposure. Complete recovery from this desensitization required more than 20 h (Oles et al 1997). It is likely to reflect a rapid endocytotic internalization of the surface receptors (Chun et al 1995).…”

Section: Introductionmentioning

confidence: 97%

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Ca2+ entry but not Ca2+ release is necessary for desensitization of ETA receptors in airway epithelial cells

Meyer

Oles

Pott

2000

Naunyn-Schmiedeberg's Arch Pharmacol

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Ca2+ transients evoked by endothelin-1 (ET-1) were measured in single cells of a human tracheal epithelial cell line using the fluorescent Ca2+ indicator fura-2. In line with a previous study, a single exposure to ET-1 (10 nM) for 10-20 s resulted in a long-lasting desensitization to a subsequent challenge by the peptide, without affecting sensitivity to agonists for other Ca2+-mobilizing receptors such as P2y or H1, respectively. In the absence of extracellular Ca2+ ET-1 elicited a Ca2+ signal of comparable amplitude as in the presence of extracellular Ca2+ but of shorter duration. Exposure to ET-1 in the absence of Ca2+ caused significantly less desensitization. Inhibition of the Ca2+ entry component of the Ca2+ transient by means of SK&F 96365, an inhibitor of Ca2+ entry, had effects comparable to Ca2+ removal. The Ca2+ transient was shortened but not significantly reduced in amplitude, and desensitization was reduced in the presence of the compound. These data demonstrate that desensitization of ET(A) receptors (ET(A)R) is promoted by transmembrane Ca2+ entry but not by Ca2+ release.

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Section: Resultssupporting

confidence: 90%

Section: Resultssupporting

confidence: 50%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

See 2 more Smart Citations

Ca2+ entry but not Ca2+ release is necessary for desensitization of ETA receptors in airway epithelial cells

Meyer

Oles

Pott

2000

Naunyn-Schmiedeberg's Arch Pharmacol

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“…Exogenously added ET-1 -as in our experimental setting -will thus cause a weaker response under conditions of an activated vascular ET system. In addition, it is also possible that in states of an activated ET system, the pressor response to exogenously added ET-1 is blunted due to a downregulation of post-receptor signaling as a consequence of the preexisting endogenous stimulation of the ET system [37,38] .…”

Section: Discussionmentioning

confidence: 99%

Lack of iNOS Impairs Endothelial Function in Endothelin-1 Transgenic Mice

Quaschning

Voß²,

Herzfeld³

et al. 2008

Kidney Blood Press Res

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Background: Endothelin-1 (ET-1) is one of the most potent biologic vasoconstrictors. Nevertheless, transgenic mice overexpressing ET-1 exhibit normal blood pressure. We hypothesized that in states of ET-1 overproduction, the lack of counterregulatory mediators such as nitric oxide (NO), produced by the inducible NO synthase (iNOS), may critically impair endothelial function and may result in blood pressure elevation. Methods: We generated crossbred animals of ET transgenic mice (ET+/+) and iNOS knockout mice (iNOS–/–) and evaluated blood pressure and endothelial function in these animals. Endothelium-dependent and -independent vascular function was assessed as relaxation/contraction of isolated preconstricted aortic rings to acetylcholine, sodium nitroprusside, and ET-1, alone or in the presence of BQ123 or BQ788. Results: Systolic blood pressure was similar in ET+/+, iNOS–/– and wild-type mice, but was significantly elevated in ET+/+ iNOS–/– crossbred animals versus ET+/+ mice. Maximum endothelium-dependent relaxation was enhanced in ET+/+ mice (95 ± 5 vs. 78 ± 5% of preconstriction in wild-type littermates; p < 0.05). Additional knockout of iNOS led to a significant decrease of endothelium-dependent relaxation in combined ET+/+ iNOS–/– animals (75 ± 6%; p < 0.05 vs. ET+/+ mice). Endothelium-independent relaxation was comparable among all groups. Maximum vascular contraction to ET-1 was reduced in ET+/+ mice (33 ± 4%), iNOS–/– mice (38 ± 5%) and ET+/+ iNOS–/– mice (44 ± 4%) to a similar extent as compared with wild-type littermates (66 ± 4%; p < 0.05). Conclusions: Our data show for the first time that in transgenic mice overexpressing human ET-1, additional knockout of iNOS results in impaired endothelium-dependent vasodilatation thus contributing to elevated blood pressure in ET+/+ iNOS–/– animals.

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Differential Desensitization of Ca 2+ Mobilization and Vasoconstriction by ET A Receptors in the Gerbil Spiral Modiolar Artery

Scherer

Wonneberger

Wangemann

2001

Journal of Membrane Biology

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Endothelins are known to be among the most potent endogenous vasoconstrictors. Vasoconstriction of the spiral modiolar artery, which supplies the cochlea, may be implicated in hearing loss and tinnitus. The purpose of the present study was to determine whether the spiral modiolar artery responds to endothelin, whether a change in the cytosolic Ca2+ concentration ([Ca2+]i) mediates the response and which endothelin receptors are present. The vascular diameter and [Ca2+]i were measured simultaneously by videomicroscopy and microfluorometry in the isolated spiral modiolar artery from the gerbil. ET-1 induced a transient [Ca2+]i increase and a strong and long-lasting vasoconstriction. The transient [Ca2+]i increase underwent rapid desensitization, was independent of extracellular Ca2+ and inhibited by the IP3-receptor blocker (75 microm) 2-aminoethoxydiphenyl borate (2-APB) and by depletion of Ca2+ stores with 10(-6) m thapsigargin. In contrast, the vasoconstriction displayed no comparable desensitization. The initial vasoconstriction was independent of extracellular Ca2+ but maintenance of the constriction depended on the presence of extracellular Ca2+. The half-maximal concentration values (EC50) for the agonists ET-1, ET-3 and sarafotoxin S6c were 0.8 nm, >10 nm and >100 nm, respectively. Affinity constants for the antagonists BQ-123 and BQ-788 were 24 nm and 77 nm, respectively. These observations demonstrate that ET-1 mediates a vasoconstriction of the gerbil spiral modiolar artery via ETA receptors and an IP3 receptor-mediated release of Ca2+ from thapsigargin-sensitive Ca2+ stores. The marked difference in desensitization between Ca2+ mobilization and vasoconstriction suggests that Ca2+ mobilization is not solely responsible for the vasoconstriction and that other signaling mechanisms must be present.

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Rapid down regulation of Ca2+ signals induced by endothelin-1 in a human bronchial epithelial cell line

Cited by 9 publications

References 37 publications

Ca2+ entry but not Ca2+ release is necessary for desensitization of ETA receptors in airway epithelial cells

Ca2+ entry but not Ca2+ release is necessary for desensitization of ETA receptors in airway epithelial cells

Lack of iNOS Impairs Endothelial Function in Endothelin-1 Transgenic Mice

Differential Desensitization of Ca 2+ Mobilization and Vasoconstriction by ET A Receptors in the Gerbil Spiral Modiolar Artery

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