Butyl benzyl phthalate blocks Ca2+ signaling and catecholamine secretion coupled with nicotinic acetylcholine receptors in bovine adrenal chromaffin cells.
Butyl benzyl phthalate (BBP), a plasticizer and an environmental pollutant, exerts genomic estrogenic-like effects via estrogen receptors. In addition to exerting genomic effects via intracellular steroid receptors, estrogen exerts non-genomic effects through interactions with membrane ion channels to lead the rapid alteration of neuronal excitability. Estradiol is known as to have modulating role on nicotinic acetylcholine receptors (nAChR). We investigated the possibility of BBP exerting non-genomic estrogenic-like effects on nAChR in bovine adrenal chromaffin cells. Our results show that BBP inhibited Ca2+ signaling induced by the nicotinic ligands carbachol, 1,1-dimethyl-4-phenyl-piperazinium iodide (DMPP) and epibatidine (IC50 levels of 4.3, 4.1, 5.4 microM, respectively) as well as high K+ solution (IC50 50.9 microM). Additionally, in the electrophysiological observations, BBP blocked the inward current coupled with nAChR under the stimulation of carbachol. We, therefore, suggest that nAChR and voltage-gated Ca2+ channels are major and minor sites, respectively, of BBP action on the plasma membrane. The inhibitory effect of BBP on nAChR was found to be both noncompetitive and reversible, remaining unchanged as nAChR ligand concentration increased and decreased after washing. BBP was 10 times more potent than estradiol in inhibiting nAChR-coupled Ca2+ signals. We conclude that BBP exerts a novel rapidly inhibitory effect on nAChR.
Liu
Pei-Shan
PS
Department of Microbiology, Soochow University, Shihlin, Taipei, Taiwan, ROC. psliu@mail.scu.edu.tw
Lin
Chih-Ming
CM
Pan
Chien-Yuan
CY
Kao
Lung-Sen
LS
Tseng
Fu-Wei
FW
D000313:Adrenal Medulla / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D002395:Catecholamines / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002417:Cattle; D019439:Chromaffin Cells / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D010795:Phthalic Acids / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000378:metabolism*
D002395:Catecholamines; D010795:Phthalic Acids; D011978:Receptors, Nicotinic; C027561:butylbenzyl phthalate