Alkylphenol endocrine disrupters inhibit IP3-sensitive Ca2+ channels.
We have investigated the influence of alkylphenol endocrine disrupters and the synthetic estrogen diethylstilbestrol (DES) on inositol-1,4,5-trisphosphate (IP(3))-sensitive Ca(2+) channels from porcine cerebellum and rat testicular membranes. All alkylphenols and DES inhibited the extent of IP(3)-induced Ca(2+) release (IICR) from both cerebellar and testicular microsomes. 4-n-nonylphenol was the most potent compound tested (IC(50), 8 microM). Inhibition of IICR was directly related to the length and hydrophobicity of the alkylphenol side chain. None of the alkylphenols or DES appeared to influence the concentration dependence of IICR nor did they have a significant effect on [3H]IP(3) binding to the membranes. An investigation of the effects of nonylphenol on the transient kinetics of IICR showed that it inhibited the rate constants for both the fast and the slow phases of IICR and also the extent of Ca(2+) release. These results illustrate another mechanism by which these environmental pollutants can disrupt endocrine function without the involvement of estrogen receptors.
Khan
Shahla Zafar
SZ
School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
Kirk
Christopher J
CJ
Michelangeli
Francesco
F
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D004054:Diethylstilbestrol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D007700:Kinetics; D008861:Microsomes / Q000378:metabolism; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013552:Swine
D015220:Calcium Channels; D004968:Estrogens, Non-Steroidal; D010636:Phenols; D004054:Diethylstilbestrol; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium