The anorexic agent dexfenfluramine causes the development of primary pulmonary hypertension in susceptible patients by an unknown mechanism that may include changes in K+-channel activity and intracellular Ca2+ concentration ([Ca2+](i)). We investigated the dose-dependent effects of dexfenfluramine on [Ca2+](i), K+ current, and membrane potential in freshly dispersed rat pulmonary artery smooth muscle cells. Dexfenfluramine caused a dose-dependent (1-1,000 μM) increase in [Ca2+](i), even at concentrations lower than those necessary to inhibit K+ currents (10 μM) and cause membrane depolarization (100 μM). The [Ca2+](i) response to 1 and 10 μM dexfenfluramine was completely abolished by pretreatment of the cells with 0.1 μM thapsigargin, whereas the response to 100 μM dexfenfluramine was reduced. CoCl2 (1 mM), removal of extracellular Ca2+, and pretreatment with caffeine (1 mM) reduced but did not abolish the response to 100 μM dexfenfluramine. We conclude that dexfenfluramine increases [Ca2+](i) in rat pulmonary artery smooth muscle cells by both release of Ca2+ from the sarcoplasmic reticulum and influx of extracellular Ca2+.
|Original language||English (US)|
|Journal||American Journal of Physiology - Lung Cellular and Molecular Physiology|
|Issue number||3 21-3|
|State||Published - Sep 1999|
- Intracellular calcium
- Potassium channels
- Sarcoplasmic reticulum