Ion channels: new targets for the next generation of tocolytics agents.
Ion channels are interesting molecules since they mediate not only uterine contraction but also uterine relaxation. We have examined the expression, function, and correlation between the large conductance calcium-activated potassium (BKCa) channel, beta2 adrenoceptor (AR), and long-lasting (L) type calcium (Ca2+) channel. These are the main channels and receptor that are involved in the uterine contraction/ relaxation process. Our evidence has shown that BKCa channel is closely correlated with beta2 AR in mediating uterine relaxation. Both proteins are situated in close proximity on the plasma membrane of human myometrium and are downregulated approximately 50% after the onset of labor. Interestingly, L type Ca2+ channel, which involves in the contraction pathway, seems to be in the same compartmentation as BKCa channel/ beta2 AR macromolecular complex. Further studies are now being conducted to identify the signaling complex components that could potentially be a target for new tocolytic agents.
Chanrachakul
Boonsri
B
Division of Maternal Fetal Medicine, Department of Obstetrics and Gynaecology, Ramathibodi Hospital, Mahidol University, Rama VI Rd, Bangkok 10400, Thailand.
D015220:Calcium Channels / Q000187:drug effects*; D005260:Female; D006801:Humans; D007752:Obstetric Labor, Premature / Q000517:prevention & control; D015221:Potassium Channels / Q000187:drug effects*; D011247:Pregnancy; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D015149:Tocolytic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D014590:Uterine Contraction / Q000187:drug effects*; D014599:Uterus / Q000187:drug effects* / Q000294:innervation
D015220:Calcium Channels; D015221:Potassium Channels; D018343:Receptors, Adrenergic, beta-2; D015149:Tocolytic Agents