Phthalates suppress the calcium signaling of nicotinic acetylcholine receptors in bovine adrenal chromaffin cells.
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.
Liu
Pei-Shan
PS
Department of Microbiology, Soochow University, Shihlin, Taipei, Taiwan, Republic of China. psliu@mail.scu.edu.tw
Lin
Chih-Ming
CM
D000313:Adrenal Medulla / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects*; D002417:Cattle; D019439:Chromaffin Cells / Q000187:drug effects* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D018722:Nicotinic Agonists / Q000494:pharmacology; D010795:Phthalic Acids / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000187:drug effects*
D018722:Nicotinic Agonists; D010795:Phthalic Acids; D011978:Receptors, Nicotinic