Mechanisms of the prostaglandin F 2α ‐induced rise in [Ca 2+ ] i in rat intrapulmonary arteries

The mechanisms by which prostaglandin F 2α (PGF 2α ) increases intracellular Ca 2+ concentration [Ca 2+ ] i in vascular smooth muscle remain unclear. We examined the role of store‐, receptor‐ and voltage‐operated Ca 2+ influx pathways in rat intrapulmonary arteries (IPA) loaded with Fura PE‐3. Low concentrations (0.01–1 μ m ) of PGF 2α caused a transient followed by a plateau rise in [Ca 2+ ] i . Both responses became maximal at 0.1 μ m PGF 2α . At higher concentrations of PGF 2α , a further slower rise in [Ca 2+ ] i was superimposed on the plateau. The [Ca 2+ ] i response to 0.1 μ m PGF 2α was mimicked by the FP receptor agonist fluprostenol, whilst the effect of 10 μ m PGF 2α was mimicked by the TP receptor agonist U‐46619. The plateau rise in [Ca 2+ ] i in response to 0.1 μ m PGF 2α was insensitive to diltiazem, and was abolished in Ca 2+ ‐free physiological salt solution, and by pretreatment with La 3+ , 2‐APB, thapsigargin or U‐73122. The rises in [Ca 2+ ] i in response to 10 μ m PGF 2α and 0.01 μ m U‐46619 were partially inhibited by diltiazem. The diltiazem‐resistant components of both of these responses were inhibited by 2‐APB and La 3+ to an extent which was significantly less than that seen for the response to 0.1 μ m PGF 2α , and were also much less sensitive to U‐73122. The U‐46619 response was also relatively insensitive to thapsigargin. When Ca 2+ was replaced with Sr 2+ , the sustained increase in the Fura PE‐3 signal to 0.1 μ m PGF 2α was abolished, whereas 10 μ m PGF 2α and 0.05 μ m U‐46619 still caused substantial increases. These results suggest that low concentrations of PGF 2α act via FP receptors to cause IP 3 ‐dependent Ca 2+ release and store operated Ca 2+ entry (SOCE). U‐46619 and 10–100 μ m PGF 2α cause a TP receptor‐mediated Ca 2+ influx involving both L‐type Ca 2+ channels and a receptor operated pathway, which differs from SOCE in its susceptibility to La 3+ , 2‐APB and thapsigargin, does not require phospholipase C activation, and is Sr 2+ permeable.