Title

Modulation of bradykinin-induced calcium changes in SH-SY5Y cells by neurosteroids and sigma receptor ligands via a shared mechanism

Document Type

Journal Article

Publication Date

11-1-2004

Journal

Synapse

Volume

54

Issue

2

DOI

10.1002/syn.20069

Keywords

(+)pentazocine; DHEA; Haloperidol; Pregnenolone; Progesterone

Abstract

In this study we investigated the effects of sigma receptor ligands and neurosteroids on bradykinin-induced intracellular calcium concentration ([Ca2+]i) changes in SH-SY5Y neuroblastoma cells. [Ca 2+]i levels in cells loaded with fura-2 were monitored with dual-wavelength ratiometric fluorescence measurement. Submicromolar concentrations of bradykinin elicited [Ca2+]i responses with a fast rise followed by a slow decline in these cells. Preincubation of low micromolar concentrations of the neurosteroids pregnenolone, dehydroepiandrosterone (DHEA), or the prototypic sigma (σ) receptor agonist (+)pentazocine potentiated bradykinin-induced [Ca2+] i changes in SH-SY5Y cells. The σ receptor antagonist haloperidol blocked the enhancing effects on [Ca2+]i by (+)pentazocine or pregnenolone. Progesterone did not significantly affect the basal [Ca2+]i level or bradykinin-induced [Ca 2+]i changes in these cells. However, coincubation of progesterone with (+)pentazocine, pregnenolone, or DHEA reversed their potentiating effects. The antagonistic effects of haloperidol and progesterone on the potentiating effects of (+)pentazocine and pregnenolone suggested that these ligands might act through a common mechanism. We further showed that progesterone, pregnenolone, and DHEA competed for [3H](+)pentazocine binding in SH-SY5Y cells with Ki values of 0.13 ± 0.03 μM, 0.98 ± 0.34 μM, and 5.2 ± 1.4 μM, respectively. Thus, the modulation of bradykinin-induced [Ca2+]i changes by neurosteroids in these cells is likely due to their actions on σ receptors. © 2004 Wiley-Liss, Inc.

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