Bvr. Sastry et al., Prostaglandin E-2 in human placenta: Its vascular effects and activation of prostaglandin E-2 formation by nicotine and cotinine, PHARMACOL, 58(2), 1999, pp. 70-86
Tobacco smoking by pregnant women increases the frequency of spontaneous ab
ortions and preterm births. Human labor is associated with enhanced intraut
erine phospholipid metabolism and production of prostaglandin E-2 (PGE(2))
which induces labor, initiates uterine contractions and maintains the homeo
stasis of placental blood flow. Therefore, we studied: (a) the influence of
nicotine and cotinine on the effects of PGE(2) on placental vasculature in
perfused human placental cotyledon, and (b) the activation of placental ph
ospholipase A(2) (PLA(2)) by nicotine and cotinine using 1-palmitoyl-2-[1-C
-14]arachidonyl-phosphatidylethanolamine (PE, 2.2 nmol) as substrate. These
studies revealed that: (1) increasing concentrations of PGE(2) (10-150 ng/
ml) increased umbilical perfusion pressure by 170 +/- 10% (n = 6) of contro
l (100%). Cotinine (2 mu g/ml) enhanced this effect at all concentrations o
f PGE(2). Nicotine (2 mu g/ml) prevented the effect of PGE(2); (2) both cot
inine (EC50 470-500 fmol/l) and nicotine (EC50 18-32 pmol/l) activated PLA(
2) in human placental tissues. These observations indicated that cotinine w
as more potent than in nicotine activating PLA(2) and potentiating the vaso
constrictive effects of PGE(2) on fetal placental circulation. Nicotine act
ivates nicotinic receptors and releases placental acetylcholine, a vasodila
tor of placental arteries. Acetylcholine stimulates muscarinic receptors of
endothelial cells resulting in the release of endothelium-derived relaxing
factor (EDRF), and possibly nitric oxide. Therefore, nicotine prevents or
abolishes the vasoconstrictive effects of PGE(2) through the release of EDR
F. Cotinine is inactive at nicotinic and muscarinic receptors. Therefore, a
ccumulation of cotinine, the major metabolite of nicotine, in fetal circula
tion may contribute to production of PGE(2) and induction of preterm labor
and spontaneous abortions.