Comparative suppression of phthalate monoesters and phthalate diesters on calcium signalling coupled to nicotinic acetylcholine receptors

Abstract

Phthalates, such as butyl benzyl phthalate (BBP), di-n-butyl phthalate (DBP), and their metabolites (mono-buyl phthalate [MBP], mono-benzyl phthalate [MBzP] and phthalic acid [PA]), are known to obstruct normal development in mammals. BBP and DBP have been reported to have estrogenic activity, while MBP and MBzP exhibit weak or no estrogenic effects. We previously showed that BBP and DBP have inhibitory roles on nicotinic acetylcholine receptors. Nicotinic acetylcholine receptors are widely distributed and have roles in developmental processes. In this study, the effects of BBP, DBP, MBP, MBzP and PA on calcium signaling coupled to nicotinic acetylcholine receptors was investigated in bovine adrenal chromaffin cells and human neuroblastoma SH-SY5Y cells. Following an epibatidine-induced [Ca2+](c) increase, the IC(50)s of BBP, DBP, MBzP and MBP were 3.41, 5.01, 432 and 695 microM in bovine adrenal chromaffin cells and 0.28, 0.44, 58 and 116 microM in human SH-SY5Y cells, respectively. Although PA suppressed the epibatidine-induced [Ca2+](c) increase, the suppression was less than with MBP. The suppression potency of phthalates was related to their chemical structures. The suppression effects of BBP, DBP, MBP and MBzP remained similar potency under chronic treatments. This study demonstrated that MBP, MBzP and PA, the metabolites of BBP and DBP, had suppressor roles on the calcium signaling pathway coupled to nicotinic receptors.