Effects of nicotine and cocaine on the release of acetylcholine from isolated human placental villi.

According to our studies, human term placenta contains about 112 nmol/g of ACh. In the present studies, isolated placental villi were suspended in Kreb's bicarbonate buffer (pH 7.4) at 37 degrees and 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/min. Cocaine in doses of 280 and 56o micrometer decreased the spontaneous release of ACh to 23, and 17 pmol/g/min, respectively. Raising the Ca2+ concentration in the Kreb's bicarbonate buffer from 2.34 to 4.64 mM, or the addition of nicotine (58 micrometer) to the bath increased the rate of release of ACh to 53 and 47 pmol/g/min, respectively. Cocaine decreased the rate of release 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 cocaine acts possibly by preventing the entry of external Ca2+ into the syncytiotrophoblast, and thereby decreases ACh release from the placental villus.