Triphenylethylene antiestrogen-induced acute relaxation of mouse duodenal muscle. Possible involvement of Ca2+ channels.

The nonsteroidal antiestrogens tamoxifen, 4-OH-tamoxifen and toremifene rapidly inhibited spontaneous contractile activity and reduced basal tone in isolated mouse duodenal muscle. Inhibition was rapid in onset ( approximately 2 min) and was not mimicked by the pure steroidal antiestrogen 7alpha-[9-[(4,4,5,5,5-pentafluoropentyl)sulfinyl]nonyl]-estra-1,3,5(10)-triene-3,17beta-diol (ICI182,780) indicating the involvement of non-genomic mechanisms. Inhibition by tamoxifen and 4-OH-tamoxifen were observed at concentrations comparable to those reached in antiestrogen adjuvant therapy. Antiestrogen-relaxed tissues showed no response to KCl depolarisation or K(+) channel blockade but displayed clear transient responses to acethylcholine or to the muscarinic receptor agonist carbachol. Frequency analysis showed that spontaneous activity could be readily restored in antiestrogen-relaxed tissues by the exposure to the L-type Ca(2+) channel agonist 1,4-dihydro-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)phenyl]-pyridine-3-carboxilic acid methyl ester (BAY K8644). Our experiments suggest that triphenylethylene antiestrogens relax duodenal intestinal muscle via a mechanism that involves inhibition of L-type Ca(2+) channels but not activation of K(+) channels.