Mechanisms of the prostaglandin F sub(2 alpha )-induced rise in [Ca super(2+)] sub(i) in rat intrapulmonary arteries

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