Article

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

Department of Pharmacology and Physiology, The George Washington University Medical Center, Washington, DC 20037, USA.
Synapse (impact factor: 2.94). 12/2004; 54(2):102-10. DOI:10.1002/syn.20069
Source: PubMed

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. [Ca2+]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 (sigma) receptor agonist (+)pentazocine potentiated bradykinin-induced [Ca2+]i changes in SH-SY5Y cells. The sigma 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 [Ca2+]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 microM, 0.98 +/- 0.34 microM, and 5.2 +/- 1.4 microM, respectively. Thus, the modulation of bradykinin-induced [Ca2+]i changes by neurosteroids in these cells is likely due to their actions on sigma receptors.

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Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

+)pentazocine potentiated bradykinin-induced [Ca2+]i changes
 
[3H]+pentazocine binding
 
basal [Ca2+]i level
 
bradykinin elicited [Ca2+]i responses
 
bradykinin-induced [Ca2+]i changes
 
bradykinin-induced intracellular calcium concentration
 
dual-wavelength ratiometric fluorescence measurement
 
fast rise
 
Ki values
 
low micromolar concentrations
 
neurosteroids pregnenolone
 
potentiating effects
 
Progesterone
 
prototypic sigma
 
SH-SY5Y cells
 
SH-SY5Y neuroblastoma cells
 
sigma receptor antagonist haloperidol
 
sigma receptor ligands
 
sigma receptors
 
Submicromolar concentrations