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.
Díaz
Mario
M
Laboratorio de Fisiología Animal, Departamento de Biología Animal, Universidad de La Laguna, 38206 Tenerife, Spain. madiaz@ull.es
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000187:drug effects* / Q000502:physiology; D020847:Estrogen Receptor Modulators / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009126:Muscle Relaxation / Q000187:drug effects* / Q000502:physiology; D013267:Stilbenes / Q000494:pharmacology*
D020746:Calcium Channels, L-Type; D020847:Estrogen Receptor Modulators; D013267:Stilbenes; C037749:triphenylethylene; D002118:Calcium