Mechanisms of the prostaglandin F2α‐induced rise in [Ca2+]i in rat intrapulmonary arteries

Abstract

The mechanisms by which prostaglandin F2α (PGF2α) increases intracellular Ca2+ concentration [Ca2+]i in vascular smooth muscle remain unclear. We examined the role of store‐, receptor‐ and voltage‐operated Ca2+ influx pathways in rat intrapulmonary arteries (IPA) loaded with Fura PE‐3. Low concentrations (0.01–1 μm) of PGF2α caused a transient followed by a plateau rise in [Ca2+]i. Both responses became maximal at 0.1 μm PGF2α. At higher concentrations of PGF2α, a further slower rise in [Ca2+]i was superimposed on the plateau. The [Ca2+]i response to 0.1 μm PGF2α was mimicked by the FP receptor agonist fluprostenol, whilst the effect of 10 μm PGF2α was mimicked by the TP receptor agonist U‐46619. The plateau rise in [Ca2+]i in response to 0.1 μm PGF2α was insensitive to diltiazem, and was abolished in Ca2+‐free physiological salt solution, and by pretreatment with La3+, 2‐APB, thapsigargin or U‐73122. The rises in [Ca2+]i in response to 10 μm PGF2α and 0.01 μm U‐46619 were partially inhibited by diltiazem. The diltiazem‐resistant components of both of these responses were inhibited by 2‐APB and La3+ to an extent which was significantly less than that seen for the response to 0.1 μm PGF2α, and were also much less sensitive to U‐73122. The U‐46619 response was also relatively insensitive to thapsigargin. When Ca2+ was replaced with Sr2+, the sustained increase in the Fura PE‐3 signal to 0.1 μm PGF2α was abolished, whereas 10 μm PGF2α and 0.05 μm U‐46619 still caused substantial increases. These results suggest that low concentrations of PGF2α act via FP receptors to cause IP3‐dependent Ca2+ release and store operated Ca2+ entry (SOCE). U‐46619 and 10–100 μm PGF2α cause a TP receptor‐mediated Ca2+ influx involving both L‐type Ca2+ channels and a receptor operated pathway, which differs from SOCE in its susceptibility to La3+, 2‐APB and thapsigargin, does not require phospholipase C activation, and is Sr2+ permeable.