Capacitative Ca2+ influx and a Ca2u+-dependent nonselective cation pathway are discriminated by genistein in mouse pancreatic acinar cells

Pfeiffer, Fatima; Schmid, Andreas; Schulz, Irene

doi:10.1007/bf01837405

Cited by 20 publications

(11 citation statements)

References 45 publications

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“…Cytoplasmic extracts pre pared from stimulated cells are capable of enhancing Ca2+ influx in unstimulated cells when the extracts are injected or applied [27,33], Based on partial purification proce dures, a putative factor (termed CIF for Ca2+ influx fac tor) was proposed to be a small-molecular-weight, phosphorylated compound [33], A requirement for phosphory lation agrees with our observations and those of others [7,22,26] that depletion-activated current is blocked by tyrosine kinase inhibitors. Although some electrophysiological evidence for a diffusible factor exists [34], activa tion of genuine I c r a c b y cell extracts has yet to be demon strated.…”

Section: Discussionsupporting

confidence: 84%

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Calcium-Release-Activated Calcium Influx in Endothelium

Davis

Sharma²

1997

J Vasc Res

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Signaling pathways activated by the tachykinin substance P (SP) were investigated in pig coronary artery endothelial cells (PCAECs). Single cells were obtained after enzymatic digestion of coronary arteries. Intracellular Ca²⁺ ([Ca²⁺]i) was measured from fura-2 fluorescence while membrane potential or ionic current was measured using patch-clamp techniques. In physiological saline solution, SP induced hyperpolarizations or outward currents which coincided with biphasic [Ca²⁺]i increases representing store release of Ca²⁺ and Ca²⁺ influx. Single channel recording protocols showed that both sources of Ca²⁺ activated a small conductance K⁺ channel, resulting in cell hyperpolarization. When outward currents were blocked by d-tubocurare, Cs⁺, or BAP-TA, an inward current was unmasked. Ion substitution protocols showed that the SP-induced inward current was (1) carried by a mixture of Ca²⁺ and Na⁺, (2) blocked by La³⁺, and (3) inactivated by high extracellular [Ca²⁺]. Tyrosine kinase inhibitors also blocked the inward current. The same current was activated by bath application of BHQ, an inhibitor of the endoplasmic reticulum Ca²⁺ ATPase, or by cell dialysis with IP3. These results suggest that the plateau phase of the agonist-activated [Ca²⁺]i increase in PCAECs reflects Ca²⁺ entry through a depletion-activated Ca²⁺ channel. The characteristics of this channel are compared to those of Ca²⁺ channels found in other nonexcitable cells.

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Section: Discussionsupporting

confidence: 84%

“…This idea has experimental support in other cell types [22], although no electrophysiological data is avail able for endothelial cells.…”

Section: Ca2* Influx Depends On Tyrosine Phosphorylationmentioning

confidence: 99%

Calcium-Release-Activated Calcium Influx in Endothelium

Davis

Sharma²

1997

J Vasc Res

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“…Among these potential modulators of capacitative Ca 2+ influx, tyrosine kinases could play an important role. Indeed, various studies have shown that tyrosine kinase inhibitors prevent the [Ca 2+ ] c response induced by thapsigargin or a Ca 2+ -mobilizing agonist (Lee et al 1993, Sargeant et al 1993, Pfeiffer et al 1995, Flemming et al 1996, Sharma & Davies 1996, Takemura et al 1997). The present work was therefore designed to assess whether, in bovine glomerulosa cells, tyrosine kinases contribute to the well characterized capacitative Ca 2+ influx and to the subsequent biological response, aldosterone biosynthesis.…”

Section: Figurementioning

confidence: 99%

The role of tyrosine kinases in capacitative calcium influx-mediated aldosterone production in bovine adrenal zona glomerulosa cells

Aptel

Burnay²,

Rossier³

et al. 1999

Journal of Endocrinology

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In adrenal glomerulosa cells, the stimulation of aldosterone biosynthesis by angiotensin II (Ang II) involves the activation of a capacitative Ca 2+ influx through calcium release-activated calcium (CRAC) channels. In various mammalian cell systems, it has been shown that CRAC channel activation and Ca 2+ entry require tyrosine kinase activity. We have therefore examined in this work whether similar mechanisms contribute to Ang II-induced mineralocorticoid biosynthesis. In fluo-3-loaded isolated bovine glomerulosa cells, two inhibitors of tyrosine kinases, genistein and methyl-2,5-dihydroxycinnamate (MDHC) (100 µM) prevented capacitative Ca 2+ entry elicited by Ang II (by 54 and 62% respectively), while the inhibitor of epidermal growth factor (EGF) receptor tyrosine kinase, lavendustin A, was without effect. Similar results were observed on Ca 2+ influx triggered by thapsigargin, an inhibitor of microsomal Ca 2+ pumps. The inhibitors blocked Ang II-stimulated pregnenolone and aldosterone production in the same rank order. In addition to its specific effect on capacitative Ca 2+ influx, genistein also affected the late steps of the steroidogenic pathway, as shown by experiments in which the rate-limiting step (intramitochondrial cholesterol transfer) was bypassed with 25-OH-cholesterol (25-OH-Chol), cytosolic calcium was clamped at stimulated levels or precursors of the late enzymatic steps were supplied. In contrast, genistin, a structural analogue of genistein devoid of tyrosine kinase inhibitory activity, was almost without effect on pregnenolone or 11-deoxycorticosterone (DOC) conversion to aldosterone. These results suggest that, in bovine adrenal glomerulosa cells, Ang II promotes capacitative Ca 2+ influx and aldosterone biosynthesis through tyrosine kinase activation.

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“…However, the role of tyrosine phosphorylation remains ambiguous as only certain tyrosine kinase inhibitors (including genistein) effectively block capacitative Ca 2ϩ entry (42). Thapsigargin-induced Ca 2ϩ entry can also occur in the absence of detectable tyrosine phosphorylation but is still inhibited by tyrosine kinase inhibitors (43), and, therefore, the role of tyrosine kinases in activation of I Ca-NS remains to be clarified.…”

Section: Fig 5 Activation Of the Mtx-sensitive Current Is Dependentmentioning

confidence: 99%

Insulinotropic Glucagon-like Peptide-1-mediated Activation of Non-selective Cation Currents in Insulinoma Cells Is Mimicked by Maitotoxin

Leech

Habener

1997

Journal of Biological Chemistry

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Maitotoxin (MTX) activates a Ca 2؉-dependent non-selective cation current (I Ca-NS ) in insulinoma cells whose time course is identical to non-selective cation currents activated by incretin hormones such as glucagon-like peptide-1 (GLP-1), which stimulate glucose-dependent insulin secretion by activating cAMP signaling pathways. We investigated the mechanism of activation of I Ca-NS in insulinoma cells using specific pharmacological reagents, and these studies further support an identity between MTX-and GLP-1-activated currents. I Ca-NS is inhibited by extracellular application of genistein, econazole, and SKF 96365. This inhibition by genistein suggests that tyrosine phophorylation may play a role in the activation of I Ca-NS . I Ca-NS is not inhibited by incubation of cells in glucose-free solution, by extracellular tetrodotoxin, nimodipine, or tetraethylammonium, or by intracellular dialysis with 4-aminopyridine, ATP, ryanodine, or heparin. I Ca-NS is also not significantly inhibited by staurosporine, which does, however, partially inhibit the MTX-induced rise of intracellular Ca 2؉ concentration. These effects of staurosporine suggest that protein kinase C may not be involved in the activation of I Ca-NS but that it may regulate intracellular Ca 2؉ release. Alternatively, I Ca-NS may have a small component that is carried through separate divalent cationselective channels that are inhibited by staurosporine. I Ca-NS is neither activated nor inhibited by dialysis with KF, KF ؉ AlF 3 or GTP␥S (guanosine 5-O-(3-thiotriphosphate)), suggesting that GTP-binding proteins do not play a major role in the activation of this current.The consensus model of glucose-stimulated insulin secretion is that closure of ATP-sensitive K ϩ channels (K [3][4][5]. One mechanism underlying this increased responsiveness is the enhanced closure of K ϩ ATP channels (2). A second mechanism by which GLP-1, pituitary adenylate cyclase-activating polypeptide (PACAP), and cAMP can induce ␤-cell depolarization is through the activation of voltageindependent, non-selective cation currents (6, 7). Similar cation currents are also activated by MTX, a polyether toxin isolated from dinoflagellates that in ␤-cells has been shown to stimulate insulin secretion and inositol trisphosphate (Ins(1,4,5)P 3 ) production (8) and to enhance the influx of monovalent cations (9).MTX-sensitive currents are activated by depletion of intracellular Ca 2ϩ stores (10), and GLP-1 enhances intracellular Ca 2ϩ mobilization through the potentiation of ryanodine-sensitive Ca 2ϩ -induced Ca 2ϩ release in ␤TC3 cells (11,12). Increased cAMP levels stimulate Ca 2ϩ release from secretory granules and reduce mitochondrial Ca 2ϩ uptake in ␤-cells (13, 14). These observations raise the possibility that the activation of non-selective cation currents by PACAP and GLP-1 may be a secondary consequence of glucose-and cAMP-dependent intracellular Ca 2ϩ release. The physiological role of Ca 2ϩ releaseactivated currents in ␤-cells remains controversial, but such currents have been s...

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Capacitative Ca2+ influx and a Ca2u+-dependent nonselective cation pathway are discriminated by genistein in mouse pancreatic acinar cells

Cited by 20 publications

References 45 publications

Calcium-Release-Activated Calcium Influx in Endothelium

Calcium-Release-Activated Calcium Influx in Endothelium

The role of tyrosine kinases in capacitative calcium influx-mediated aldosterone production in bovine adrenal zona glomerulosa cells

Insulinotropic Glucagon-like Peptide-1-mediated Activation of Non-selective Cation Currents in Insulinoma Cells Is Mimicked by Maitotoxin

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