Increased sensitivity of rat myometrium to the contractile effect of platelet activating factor before delivery.
1. The contractile effects of platelet activating factor (PAF) were compared in the myometrium isolated from non-pregnant and pregnant rats. 2. In the non-pregnant myometrium, PAF, at a concentration of 0.1 microM, did not change muscle tension and induced only a small transient contraction at 10 microM. 3. The contractile responses to PAF increased with the progress of gestation. In the late pregnant myometrium (21 day after gestation), PAF (0.1 nM-10 microM) induced large and relatively sustained contractions. The threshold concentration of PAF was decreased by approximately 10,000 times and the maximum contraction was increased 5 times by day 21 of gestation. 4. PAF (10 microM) increased the cytosolic Ca2+ concentration ([Ca2+]i) and muscle contraction to levels higher than those induced by high K+ in the pregnant rat myometrium (day 21). Verapamil (10 microM), a voltage-dependent Ca2+ channel blocker, decreased the stimulated [Ca2+]i and muscle tension to 49.6% and 22.7%, respectively, while the same concentration of verapamil completely inhibited the high K(+)-induced responses. 5. PAF (10 microM) induced a transient increase in [Ca2+]i with no contraction in the absence of external Ca2+ in the pregnant myometrium (day 21). 6. These results suggest that PAF induces contraction in rat myometrium by increasing Ca2+ influx. Although PAF released Ca2+ from stored sites, this Ca2+ does not seem to contribute to the PAF-induced contraction. Our major finding is that the sensitivity of the myometrium to PAF increased after gestation and that this may play a role in delivery.
Kim
B K
BK
Department of Veterinary Pharmacology, Faculty of Agriculture, University of Tokyo, Japan.
Ozaki
H
H
Lee
S M
SM
Karaki
H
H
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D009215:Myometrium / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014590:Uterine Contraction / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D010972:Platelet Activating Factor; D014700:Verapamil; D002118:Calcium