Calcium mobilization and Na<sup>+</sup>/H<sup>+</sup> antiport activation by endothelin in human skin fibroblasts

Gardner, J. P.; Maher, Elizabeth A.; Aviv, Abraham

doi:10.1016/0014-5793(89)81713-2

Cited by 21 publications

(9 citation statements)

References 24 publications

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“…Similar results were obtained in nonquiescent SKMBs that were not deprived of FBS for 24 hours before the Caj measurements (not shown). These observations differ from those in cultured human fibroblasts, 18 myometrial cells, 17 and VSMCs, 28 in which ET-evoked transients were substantially higher in Ca 2+ -containing than in Ca 2+ -free medium. The ET-evoked Ca, response of the SKMBs also differed from that of smooth muscle cells 17 - 28 by its insensitivity to the Ca 2+ channel blockers verapamil, nicardipine, and diltiazem (Fig 1C).…”

Section: Human Skmbscontrasting

confidence: 98%

Endothelin mobilizes calcium and enhances glucose uptake in cultured human skeletal myoblasts and L6 myotubes.

Yang¹,

Fekete²,

Gardner³

et al. 1994

Hypertension

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In this study we used endothelin as a paradigm to explore the concept that some vasoactive agents, acting through mobilization of Ca 2+ and stimulation of protein kinase C, can interact with human skeletal muscle and modify its glucose transport. Cultured human skeletal myoblasts from the vastus lateralis demonstrated two subclasses of high-affinity endothelin receptors and a robust increase in cytosolic free Ca 2+ upon exposure to endothelin. The endothelin-evoked rise in cytosolic free Ca 2+ primarily resulted from Ca 2+ mobilization from intracellular organelles. Both endothelin and insulin enhanced [ 3 H]deoxy-D-glucose uptake in human myoblasts, but their effects were not additive. These findings also were observed in differentiated myotubes of L6 skeletal muscle E ssential hypertension is marked by insulin resistance resulting from altered glucose metabolism in skeletal muscles. 14 Altered glucose metabolism may relate to hemodynamic factors, including circulating vasoactive agents responsible for blood flow distribution between insulin-sensitive and insulininsensitive tissues.5 Alternatively, it could reflect perturbations in the immediate environment of skeletal muscles that are caused by a dysfunctional vascular endothelium. The vascular endothelium plays a central function in regulating vascular tone through the release of vasoactive agents. 6 ' 7 Thus, an imbalance between vasoconstrictors and vasodilators of endothelial origin could provoke peripheral vasoconstriction, increased peripheral vascular resistance (PVR), and hypertension. 7 ' 8 We postulate that a number of endothelial factors, acting on vascular smooth muscle cells (VSMCs), also interact with skeletal muscle cells to alter glucose metabolism through the same cellular pathways that promote the increase in the PVR. The action of endothelin (ET), a potent vasoconstrictor of endothelial origin, 911 was used to test this hypothesis. Although the systemic infusion of ET can produce hypertension in the rat, 12 a controversy exists as to whether the circulating levels of this factor are increased in essential hypertension. Moreover, it is uncertain whether elevated levels of ET cause hypertension in humans (reviewed in Reference 7). It may well be that the plasma levels of ET reflect a spillover from a variety of

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Section: Human Skmbscontrasting

confidence: 98%

Endothelin mobilizes calcium and enhances glucose uptake in cultured human skeletal myoblasts and L6 myotubes.

Yang¹,

Fekete²,

Gardner³

et al. 1994

Hypertension

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“…To our knowledge, the present study is the first study concerning an inhibitory effect of endothelins on [Ca2J]i transients. In addition, endothelins elicit pHi changes in skin fibroblasts and brain capillary endothelial cells (Gardner et al, 1989;Vigne et al, 1991) while we demonstrate here that they affect neither platelet pHi nor the activity of the Na+/H' exchange. This constitutes an example of the different endothelin effects on various cell types.…”

Section: Discussioncontrasting

confidence: 56%

“…In various cell types, an increase in [Ca2+], constitutes a common pathway of signal transduction for members of the endothelin peptide family (Van Renterghem et al, 1988;Gardner et al, 1989;. To our knowledge, the present study is the first study concerning an inhibitory effect of endothelins on [Ca2J]i transients.…”

Section: Discussionmentioning

confidence: 74%

In vitro inhibition by endothelins of thrombin‐induced aggregation and Ca²⁺ mobilization in human platelets

Astarie-Dequeker

Iouzalen

David‐Dufilho

et al. 1992

British J Pharmacology

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The in vitro effects of endothelins (ET‐1 and ET‐3) on human platelets were investigated by measurement of the aggregatory responses of washed platelets to thrombin and by the determination of cytosolic pH (pHi) and free Ca2+ concentration ([Ca2+]i) determined with the fluorescent indicators, BCECF and Fura‐2. ET‐1 and ET‐3 at concentrations ranging from 10−10 to 5 × 10−7 m, did not promote platelet aggregation but inhibited in a dose‐dependent manner the aggregation induced by 0.05 u ml−1 thrombin (P < 0.002 and < 0.001, respectively) with maximal effects reached at 10−8 m (17 ± 3 and 15 ± 2%, n = 11, P = 0.002 for each). Even at 5 × 10−7 m, ET‐1 and ET‐3 did not cause a measurable change in basal [Ca2+]i and pHi. When tested in combination with thrombin, 5 × 10−7 m ET‐1 and ET‐3 decreased the transient peak of [Ca2+]i by 17 ± 7 and 28 ± 7% (n = 7 and 11, P = 0.03 and P = 0.002). No effect on pHi variations was detected. In the virtual absence of external Ca2+, 5 × 10−7 m ET‐3 inhibited the peak of [Ca2+]i by 18 ± 6% (n = 6, P = 0.02). The anti‐aggregating agents, prostacyclin (PGI2, 10−8−10−7 m) and nitroprusside (NP, 10 ng‐50 μg l−1) also induced a dose‐dependent inhibition of the thrombin‐induced [Ca2+]i peak (P = 0.001 for each). A combination of 10−9 m PGI2 and 10 ng l−1 NP augmented the inhibitory effect of each drug (PGI2 alone 52 ± 11, plus NP 90 ± 2; NP alone 26 ± 4, plus PGI2 69 ± 5% inhibition of [Ca2+]i peak, n = 6 for each, P < 0.01 and P < 0.001, respectively). Platelet preincubation with 5 × 10−7 m ET‐3 increased by 34 ± 11% (n = 6, P = 0.014) the inhibitory effect of NP 10 ng l−1 without a significant influence on the PGI2 effect. In conclusion, endothelins ET‐1 and ET‐3 can reduce in vitro the aggregating response of human platelets to thrombin by a mechanism that is probably due to decrease Ca2+ mobilization.

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“…ET increases intracellular pH of many cell types in vitro including skin fibroblasts (124), platelets (451), vascular smooth muscle (172), glomerular mesangial (407), cardiac myocyte (470) and kidney epithelial cells (469). ET increases Na + /H + antiporter activity in kidney epithelial membrane vesicles (93) and cortical slices (144) and is the cell membrane H + transporter that is most consistently influenced by ET in these indicated cell types.…”

Section: Et and Acid/base Transportmentioning

confidence: 99%

Physiology of Endothelin and the Kidney

Kohan

Inscho

Wesson

et al. 2011

Comprehensive Physiology

104

136

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Since its discovery in 1988 as an endothelial cell-derived peptide that exerts the most potent vasoconstriction of any known endogenous compound, endothelin (ET) has emerged as an important regulator of renal physiology and pathophysiology. This review focuses on how the ET system impacts renal function in health; it is apparent that ET regulates multiple aspects of kidney function. These include modulation of glomerular filtration rate and renal blood flow, control of renin release, and regulation of transport of sodium, water, protons and bicarbonate. These effects are exerted through ET interactions with almost every cell type in the kidney, including mesangial cells, podocytes, endothelium, vascular smooth muscle, every section of the nephron, and renal nerves. In addition, while not the subject of the current review, ET can also indirectly affect renal function through modulation of extrarenal systems, including the vasculature, nervous system, adrenal gland, circulating hormones and the heart. As will become apparent, these pleiotropic effects of ET are of fundamental physiologic importance in the control of renal function in health. In addition, to help put these effects into perspective, we will also discuss, albeit to a relatively limited extent, how alterations in the ET system can contribute to hypertension and kidney disease.

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Calcium mobilization and Na⁺/H⁺ antiport activation by endothelin in human skin fibroblasts

Abstract: Endothelin; Growth factor; (Human skin fibroblast)

Cited by 21 publications

References 24 publications

Endothelin mobilizes calcium and enhances glucose uptake in cultured human skeletal myoblasts and L6 myotubes.

Endothelin mobilizes calcium and enhances glucose uptake in cultured human skeletal myoblasts and L6 myotubes.

In vitro inhibition by endothelins of thrombin‐induced aggregation and Ca²⁺ mobilization in human platelets

Physiology of Endothelin and the Kidney

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Calcium mobilization and Na+/H+ antiport activation by endothelin in human skin fibroblasts

Abstract: Endothelin; Growth factor; (Human skin fibroblast)

Cited by 21 publications

References 24 publications

Endothelin mobilizes calcium and enhances glucose uptake in cultured human skeletal myoblasts and L6 myotubes.

Endothelin mobilizes calcium and enhances glucose uptake in cultured human skeletal myoblasts and L6 myotubes.

In vitro inhibition by endothelins of thrombin‐induced aggregation and Ca2+ mobilization in human platelets

Physiology of Endothelin and the Kidney

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Product

Resources

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Calcium mobilization and Na⁺/H⁺ antiport activation by endothelin in human skin fibroblasts

In vitro inhibition by endothelins of thrombin‐induced aggregation and Ca²⁺ mobilization in human platelets