Prolongation of parturition in the pregnant rat following treatment with a platelet activating factor receptor antagonist.
The presence of platelet activating factor (PAF) in amniotic fluid of women only in labor is indicative of a role for PAF in parturition. In addition, stimulated amnion membrane produces both PAF and prostaglandin E2, each of which is capable of inducing myometrial contraction. To evaluate the involvement of PAF in the process of parturition, we administered the PAF receptor antagonist, L-659,989, to 17-day timed pregnant rats and followed the events of labor and delivery. Administration by mouth with L-659,989 of three concentrations (1.6, 16, and 48 mg/kg/day) did not alter the gestational period; however, the duration of parturition was increased from 2-fold to 5-fold by such treatment. No toxicity of the analog was apparent; treated dams showed no signs of morbidity, and fetal mortality was not significantly altered by treatment with the antagonist. Based on these experiments, it is suggested that the PAF receptor antagonist interferes with the normal progression of events of parturition and that PAF is an integral mediator in initiating the myometrial contraction necessary for expulsion of the fetus.
Zhu
Y P
YP
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas 75235-9038.
Hoffman
D R
DR
Hwang
S B
SB
Miyaura
S
S
Johnston
J M
JM
D000818:Animals; D005260:Female; D005663:Furans / Q000494:pharmacology; D005865:Gestational Age; D007743:Labor, Obstetric / Q000187:drug effects / Q000502:physiology*; D010972:Platelet Activating Factor / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology; D043562:Receptors, G-Protein-Coupled; D013997:Time Factors
D005663:Furans; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; C054893:L 659989