EFFECTS OF NICOTINE AND COCAINE ON RELEASE OF ACETYLCHOLINE FROM ISOLATED HUMAN PLACENTAL VILLI

Abstract

Human term placenta was shown previously to contain about 112 nmol/g of ACh. Isolated placental villi were suspended in Kreb''s bicarbonate buffer (pH 7.4) at 37.degree.. Acetylcholine (ACh) released into the medium was analyzed by gas chromatography. The spontaneous release of ACh into the medium was linear with time and was 35 pmol/g per min. Cocaine in doses of 280 and 560 .mu.M decreased the spontaneous release of ACh to 23, and 17 pmol/g per min, respectively. Raising the Ca2+ concentration in the Kreb''s bicarbonate buffer from 2.34-4.64 mM or the addition of nicotine (58 .mu.M) to the bath increased the rate of release of ACh to 53 and 47 pmol/g per min, respectively. Cocaine decreased the release rate of ACh even in the presence of Ca2+ or nicotine. ACh was not released when Ca2+ was absent in the medium. Nicotine did not stimulate the release of ACh in the Ca2+ free medium. High concentrations of K+ increased ACh release in the presence of Ca2+ and it did not have any effect on ACh release in the absence of Ca2+. These observations indicate that external Ca2+ is required for the release of ACh, and that cocaine acts possibly by preventing the entry of external Ca2+ into the syncytiotrophoblast, and thereby decreases ACh release from the placental villus.