title: Effects of nonylphenol on the calcium signal and catecholamine secretion coupled with nicotinic acetylcholine receptors in bovine adrenal chromaffin cells.
abstract: 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 Ca(2+)-ATPase. Estrogen has modulatory roles on ligand-gated ion channels, such as nicotinic acetylcholine receptors (nAChRs). Ca(2+)-ATPase inhibitors can modulate the cytosolic calcium concentration ([Ca(2+)](c)]) and thus can affect the calcium signaling coupled with nAChRs. Therefore, NP is predicted to have complex effects on the Ca(2+) signaling and secretion coupled with nAChRs. This study investigated these effects using bovine adrenal chromaffin cells. The results show that NP suppressed the Ca(2+) signaling coupled with nAChRs and voltage-operated Ca(2+) channels in a dose-dependent manner, with IC(50)s of 1 and 5.9 microM, respectively. Estradiol exhibits similar suppression but much lower inhibitory potencies. NP alone induced a transient rise in [Ca(2+)](c) in the presence or absence of extracellular calcium. Thapsigargin, an endoplasmic reticulum Ca(2+)-ATPase inhibitor, partially suppressed the [Ca(2+)](c) rise induced by NP, but NP totally blocked the [Ca(2+)](c) rise induced by thapsigargin. This illustrates that NP can cause Ca(2+) release from thapsigargin-insensitive pools. Thapsigargin suppressed the Ca(2+) signaling coupled with nAChRs but increased that coupled with voltage-operated Ca(2+) channels. We propose that three routes are responsible for the effects of NP on nAChRs: named receptor channels, voltage-gated Ca(2+) channels, and Ca(2+)-induced Ca(2+) release. Three routes are related to the characteristics of NP as steroid-like compounds and Ca(2+)-ATPase inhibitor.
authors: Department of Microbiology, Soochow University, Shihlin, Taipei, Taiwan, ROC. pslediting@mail.scu.edu.tw
authors: Pei-Shan
authors: PS
authors: Liu
authors: Ging-Hui
authors: GH
authors: Liu
authors: Wei-Liang
authors: WL
authors: Chao
mesh_terms: D000313:Adrenal Medulla / Q000166:cytology; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000502:physiology; D020013:Calcium Signaling / Q000187:drug effects*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism; D010636:Phenols / Q000737:chemistry / Q000633:toxicity*; D011189:Potassium Chloride / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000502:physiology*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D015220:Calcium Channels; D002395:Catecholamines; D010636:Phenols; D011725:Pyridines; D011978:Receptors, Nicotinic; D004958:Estradiol; D004246:Dimethylphenylpiperazinium Iodide; D011189:Potassium Chloride; D019284:Thapsigargin; C025256:nonylphenol; D002217:Carbachol; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; C082748:epibatidine; D002118:Calcium; D009638:Norepinephrine; D004837:Epinephrine