Details

Autor(en) / Beteiligte

• Sastry, B.V. Rama
• Hemontolor, M.E.
• Olenick, Molly

Titel

Prostaglandin E2 in Human Placenta: Its Vascular Effects and Activation of Prostaglandin E2 Formation by Nicotine and Cotinine

Ist Teil von

• Pharmacology, 1999-02, Vol.58 (2), p.70-86

Ort / Verlag

Basel, Switzerland: S. Karger AG

Erscheinungsjahr

1999

Quelle

MEDLINE

Beschreibungen/Notizen

• Tobacco smoking by pregnant women increases the frequency of spontaneous abortions and preterm births. Human labor is associated with enhanced intrauterine phospholipid metabolism and production of prostaglandin E 2 (PGE 2 ) which induces labor, initiates uterine contractions and maintains the homeostasis 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 phospholipase A 2 (PLA 2 ) by nicotine and cotinine using 1-palmitoyl-2-[1- 14 C]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 control (100%). Cotinine (2 µg/ml) enhanced this effect at all concentrations of PGE 2 . Nicotine (2 µg/ml) prevented the effect of PGE 2 ; (2) both cotinine (EC 50 470–500 fmol/l) and nicotine (EC 50 18–32 pmol/l) activated PLA 2 in human placental tissues. These observations indicated that cotinine was more potent than in nicotine activating PLA 2 and potentiating the vasoconstrictive effects of PGE 2 on fetal placental circulation. Nicotine activates nicotinic receptors and releases placental acetylcholine, a vasodilator 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 EDRF. Cotinine is inactive at nicotinic and muscarinic receptors. Therefore, accumulation of cotinine, the major metabolite of nicotine, in fetal circulation may contribute to production of PGE 2 and induction of preterm labor and spontaneous abortions.