Ca²⁺‐induced Ca²⁺ release in insulin‐secreting cells

Abstract

The sulphydryl reagent thimerosal (50/~M) released Ca '+ from a non-mitoehondrial intraeellalar Ca:" pool in a dose.dependent manner in pgrmeabilizoa insalin-~ceretin 8 RINmSF cells. Thi~ release was reversed after addition of the reducing agent dithiothreitol. Ca:" was releas,,M from an Ins(l.4,5)P;-insensitive pool, since release was observed even after depletion of the lns(I,4,5)P~-sensitive pool by a supramaximal dose of lns(2.4,5)P~ or thapsigargin. The lns(I.4,5)P~-sensitive pool remained essentially unaltered by thimerosal. Thimero~al.induced Ca :~ release was potentiated by caffeine. These findings suggest the existence of Ca"*-induced Ca:" release also in insulin-secreting cells.

Ca2+-induced Ca2+ Release from the Endoplasmic Reticulum Amplifies the Ca2+ Signal Mediated by Activation of Voltage-gated L-type Ca2+ Channels in Pancreatic β-Cells

“…the plasma membrane Ca 2ϩ channels and the ER Ca 2ϩ channels. ␤-Cells possess the requisite molecular components required for mediating CICR (5,10). However, the issue of whether ER Ca 2ϩ stores and the associated Ca 2ϩ channels participate in the depolarization-induced Ca 2ϩ signaling in intact ␤-cells has remained an open question.…”

“…Both of these channels can be considered to be Ca 2ϩ -gated Ca 2ϩ channels, raising the possibility that depolarization-induced Ca 2ϩ signaling may be amplified by Ca 2ϩ release through these channels. CICR has been considered in ␤-cells from indirect evidence (10) ing Ca 2ϩ into the cytoplasm, a process that is likely to involve CICR.…”

Nitric oxide induces intracellular Ca2+ mobilization and increases secretion of incorporated 5‐hydroxytryptamine in rat pancreatic β‐cells

“…From this study, the pharmacological activator of the RyR, caffeine, induced transient increases in the [Ca2+]~ of isolated rat B-cells, and the NO-induced Ca 2+ response was blocked by preincubation with antagonising concentrations of ryanodine. From previous studies, the sulfhydryl reagent thimerosal, an activator of CICR, has been shown to release Ca 2+ from an Ins(1,4,5)P3-insensitive pool in the insulin secreting cell line, RINm5F [17], and in mouse pancreatic Bcells [18]. Also, it has been suggested that the putative physiological effector of the RyR, cyclic-ADP-ribose (cADPR) [19], not only mobilizes Ca 2+, but also stimulates insulin secretion, and is synthesised in response to D-glucose in rat B-cells [20].…”

“…Also, it has been suggested that the putative physiological effector of the RyR, cyclic-ADP-ribose (cADPR) [19], not only mobilizes Ca 2+, but also stimulates insulin secretion, and is synthesised in response to D-glucose in rat B-cells [20]. Although the physical and functional nature of Ca > stores in B-cells are poorly defined, previous work suggests that Ins(1,4,5)P 3 sensitive and insensitive Ca 2+ stores coexist in B-cells [15,17,18]. Therefore, it is possible that ryanodine and Ins(1,4,5)P3 sensitive stores are distinct entities in these cells, and that interplay between these may be involved in both CICR, and oscillations in [Ca2+]i, as has been suggested in other cells [21].…”

Redox modulation of intracellular free calcium concentration in thyroid FRTL-5 cells: evidence for an enhanced extrusion of calcium

“…Of these compounds, several oxidizing or alkylating compounds have been investigated extensively. Thimerosal and t-butyl hydroperoxide (tBHP) in particular have been shown to be potent modulators of the release of sequestered calcium, apparently by sensitizing the IP $ receptor to resting levels of IP $ [4][5][6][7][8], and by sensitizing the ryanodine receptor [9][10][11]. Thimerosal also activates I CRAC [12].…”