کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2597011 | 1132562 | 2008 | 9 صفحه PDF | دانلود رایگان |

Nonylphenol (NP) is the most critical metabolite of alkylphenol polyethoxylate detergents. NP is known as an endocrine disruptor with estrogenic activities and as an inhibitor of endoplasmic reticulum Ca2+-ATPase. Estrogen has modulatory roles on ligand-gated ion channels, such as nicotinic acetylcholine receptors (nAChRs). Ca2+-ATPase inhibitors can modulate the cytosolic calcium concentration ([Ca2+]c]) and thus can affect the calcium signaling coupled with nAChRs. Therefore, NP is predicted to have complex effects on the Ca2+ signaling and secretion coupled with nAChRs. This study investigated these effects using bovine adrenal chromaffin cells. The results show that NP suppressed the Ca2+ signaling coupled with nAChRs and voltage-operated Ca2+ channels in a dose-dependent manner, with IC50s of 1 and 5.9 μM, respectively. Estradiol exhibits similar suppression but much lower inhibitory potencies. NP alone induced a transient rise in [Ca2+]c in the presence or absence of extracellular calcium. Thapsigargin, an endoplasmic reticulum Ca2+-ATPase inhibitor, partially suppressed the [Ca2+]c rise induced by NP, but NP totally blocked the [Ca2+]c rise induced by thapsigargin. This illustrates that NP can cause Ca2+ release from thapsigargin-insensitive pools. Thapsigargin suppressed the Ca2+ signaling coupled with nAChRs but increased that coupled with voltage-operated Ca2+ channels. We propose that three routes are responsible for the effects of NP on nAChRs: named receptor channels, voltage-gated Ca2+ channels, and Ca2+-induced Ca2+ release. Three routes are related to the characteristics of NP as steroid-like compounds and Ca2+-ATPase inhibitor.
Journal: Toxicology - Volume 244, Issue 1, 3 February 2008, Pages 77–85