Role of the calcium channel in blastocyst implantation: a novel contraceptive target.
The proinflammatory blastocyst implantation cascade involves important mediators like prostaglandins (PG). The influx of calcium via the calcium channel acts as a trigger for the activation of the PG synthesis pathway. Hence, it was hypothesized that calcium channel blockers that are known to possess anti-inflammatory activity may interfere with normal implantation. Pregnant Swiss albino mice (Mus musculus) were treated with diltiazem (1) 4 mg/kg, po on days 1-6 of pregnancy, n=6/day) or (2) at the implantation site (25 microg/animal) via intrauterine injection in the right horn at 5:00 pm on day 4. The intact uterus was used to assay lipid peroxidation and superoxide dismutase activity as markers of membrane fluidity or to observe the day 15 fetus. Oral diltiazem treatment in therapeutic dosage before and during the implantation period did not cause any change in normal uterine milieu during the window of implantation. When injected into the uterine lumen 12-14 h before the average implantation time, however, a complete failure in implantation was observed. Thus, the site specific action of diltiazem may be blocking prostaglandin synthesis, hence causing implantation failure. Oral diltiazem treatment did not mimic this action, indicating that although orally safe in pregnancy in therapeutic dosage, calcium channel blockers may provide a new and yet unknown target in female contraceptive research.
Banerjee
Aryamitra
A
Department of Pharmacology and Toxicology, B. V. Patel Pharmaceutical Education and Research Development Centre, SG Highway, Thaltej, Ahmedabad, Gujarat, India.
Padh
Harish
H
Nivsarkar
Manish
M
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology*; D003271:Contraceptive Agents, Female / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology*; D010064:Embryo Implantation / Q000187:drug effects*; D005260:Female; D015227:Lipid Peroxidation; D051379:Mice; D011247:Pregnancy; D013482:Superoxide Dismutase / Q000378:metabolism; D014599:Uterus / Q000187:drug effects
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D003271:Contraceptive Agents, Female; D016718:Arachidonic Acid; D013482:Superoxide Dismutase; D004110:Diltiazem