Phthalates suppress the calcium signaling of nicotinic acetylcholine receptors in bovine adrenal chromaffin cells

Liu, PS; Lin, CM

HERO ID

789660

Reference Type

Journal Article

Year

2002

Language

English

PMID

12387748

HERO ID 789660
In Press No
Year 2002
Title Phthalates suppress the calcium signaling of nicotinic acetylcholine receptors in bovine adrenal chromaffin cells
Authors Liu, PS; Lin, CM
Journal Toxicology and Applied Pharmacology
Volume 183
Issue 2
Page Numbers 92-98
Abstract Researchers have recently reported on the nongenomic action of estrogen via membrane receptors and ion channels, especially nicotinic acetylcholine receptors (nAChR). We studied the nongenomic effects of eight phthalates (an endocrine disrupter that expresses estrogen-like activity through estrogen receptors): di-n-ethyl (DEP), di-n-propyl (DPrP), di-n-butyl (DBP), benzyl-n-butyl (BBP), di-n-pentyl (DPP), di-n-hexyl (DHP), dicyclohexyl (DCHP), and di-(2-ethylhexyl) (DEHP). Specifically, we looked at their individual effects on cytosolic free calcium concentration rise induced by three nAChR agonists: carbachol, 1,1-dimethyl-4-phenyl-piperazinium iodide, and epibatidine. Results show that all of the tested phthalates suppressed nAChR-coupled Ca(2+) response. Strongest to weakest potencies were observed as DPP --> BBP --> DBP --> DCHP --> DHP --> DPrP --> DEHP --> DEP. DPP, DBP, and BBP were 10 times more potent than estradiol. We suggest that phthalate potency was associated with its chemical structure, since (a) the most effective phthalates had dialkyl group carbon numbers of C4 or C5, with shorter or longer numbers resulting in decreased potency, and (b) the presence of an alkyl ring or phenoic structure resulted in increasing potency. Because of the similarity between this relationship and estrogen receptor-binding potency, we suggest that the inhibitory effect of phthalates on nAChR-coupled Ca(2+) response is an indication of their nongenomic estrogen-like activity.
Doi 10.1006/taap.2002.9466
Pmid 12387748
Wosid WOS:000178127000003
Url http://www.sciencedirect.com/science/article/pii/S0041008X02994664
Is Certified Translation No
Dupe Override No
Comments Source: Web of Science WOS:000178127000003
Is Public Yes
Language Text English
Keyword Adrenal Medulla/cytology/ drug effects/metabolism; Animals; Calcium Signaling/ drug effects; Cattle; Chromaffin Cells/ drug effects/metabolism; Chromatography, High Pressure Liquid; Nicotinic Agonists/pharmacology; Phthalic Acids/ pharmacology; Receptors, Nicotinic/ drug effects
Is Qa No