Butyl benzyl phthalate blocks Ca2+ signaling coupled with purinoceptor in rat PC12 cells.

Butyl benzyl phthalate (BBP) is a plasticizer and causes public concern because of its genomic estrogenic effects via estrogen receptors. We previously found that BBP has non-genomic effects, exerting inhibitory effects on the functional activities of nicotinic acetylcholine receptors (nAChR) in bovine adrenal chromaffin cells. nAChR belongs to the superfamily of neurotransmitter-gated channels, so does P2X purinoceptor that is widely distributed in the nervous system and play a role in pain reactions. In this study, we investigated the effects of BBP on the change of [Ca2+]c (cytosolic calcium ion concentration) under the stimulation of purinoceptors in PC12 cells and found that BBP inhibited ATP-induced [Ca2+]c rise (IC50=8.3 microM). The inhibitory rate of BBP remained under the increase of ATP concentration; therefore, the possibility of competitive inhibition was excluded. The inhibition of BBP on P2Y was excluded because its inhibition on ATP-induced [Ca2+]c rise was not found in the absence of extracellular Ca2+. BBP might have some actions on voltage-operated Ca2+ channels (VOCCs) since BBP inhibited the Ca2+ signaling responding to high K+ stimulation (IC50=1.2 microM). We suggest that BBP inhibits the ATP-induced [Ca2+]c rise via its non-competitive inhibition on P2X purinoceptors and VOCCs in the plasma membrane.