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Modulation of bradykinin‐induced calcium changes in SH‐SY5Y cells by neurosteroids and sigma receptor ligands via a shared mechanism
Author(s) -
Hong Weimin,
Nuwayhid Samer J.,
Werling Linda L.
Publication year - 2004
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20069
Subject(s) - neuroactive steroid , bradykinin , chemistry , mechanism (biology) , biophysics , modulation (music) , receptor , calcium , pharmacology , neuroscience , biochemistry , biology , physics , gabaa receptor , organic chemistry , quantum mechanics , acoustics
In this study we investigated the effects of sigma receptor ligands and neurosteroids on bradykinin‐induced intracellular calcium concentration ([Ca 2+ ] 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 [Ca 2+ ] 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 [Ca 2+ ] i changes in SH‐SY5Y cells. The σ receptor antagonist haloperidol blocked the enhancing effects on [Ca 2+ ] i by (+)pentazocine or pregnenolone. Progesterone did not significantly affect the basal [Ca 2+ ] 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 [ 3 H](+)pentazocine binding in SH‐SY5Y cells with K i 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 [Ca 2+ ] i changes by neurosteroids in these cells is likely due to their actions on σ receptors. Synapse 54:102–110, 2004. © 2004 Wiley‐Liss, Inc.