[Effects of tamoxifen on the voltage-dependent ionic currents in mouse colonic smooth muscle cells].
OBJECTIVE
Tamoxifen is a widely used anticancer drug for breast cancer with frequent gastrointestinal side effects. Changes in gastrointestinal motility is associated with altered activities of membrane ion channels. Ion channels have important role in regulating membrane potential and cell excitability. This study was performed to investigate the effects of tamoxifen on the membrane ionic currents in colonic smooth muscle cells.


METHODS
Murine colonic smooth muscle cells were isolated from the proximal colon using collagenase, and the membrane currents were recorded using a whole-cell patch clamp technique.


RESULTS
Two types of voltage-dependent K(+) currents were recorded (A-type and delayed rectifier K(+) currents). Tamoxifen inhibited both types of voltage-dependent K(+) currents in a dose-dependent manner. However, tamoxifen did not change the half-inactivation potential and the recovery time of voltage-dependent K(+) currents. Chelerythrine, a protein kinase C inhibitor or phorbol 12, 13-dibutyrate, a protein kinase C activator did not affect the voltage-dependent K(+) currents. Guanosine 5'-O-(2-thio-diphosphate) did not affect the tamoxifen-induced inhibition of voltage-dependent K(+) currents. Tamoxifen inhibited voltage-dependent Ca(2+) currents completely in whole-test ranges.


CONCLUSIONS
These results suggest that tamoxifen can alter various membrane ionic currents in smooth muscle cells and cause some adverse effects on the gastrointestinal motility.
Lee
Dong Min
DM
Department of Internal Medicine, Chosun University College of Medicine, Gwangju, Korea.
Chang
Sung Jong
SJ
Park
Chan Guk
CG
Kim
Man Woo
MW
Lim
Gun Han
GH
Choi
Seok
S
Yeum
Cheol Ho
CH
Yoon
Pyung Jin
PJ
Jun
Jae Yeoul
JY
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects; D003106:Colon / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008564:Membrane Potentials; D051379:Mice; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects*; D013629:Tamoxifen / Q000494:pharmacology*
D018931:Antineoplastic Agents, Hormonal; D015220:Calcium Channels; D015221:Potassium Channels; D013629:Tamoxifen