Mechanisms of PGF2α induced rises in [Ca2+]i in rat intrapulmonary arteries

P Aaronson, V Snetkov, G Knock, L Baxter, G Thomas, JPT Ward

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    34 Citations (Scopus)


    The mechanisms by which prostaglandin F2 (PGF2) 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 PGF2 caused a transient followed by a plateau rise in [Ca2+]i. Both responses became maximal at 0.1 μm PGF2. At higher concentrations of PGF2, a further slower rise in [Ca2+]i was superimposed on the plateau. The [Ca2+]i response to 0.1 μm PGF2 was mimicked by the FP receptor agonist fluprostenol, whilst the effect of 10 μm PGF2 was mimicked by the TP receptor agonist U-46619. The plateau rise in [Ca2+]i in response to 0.1 μm PGF2 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 PGF2 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 PGF2, 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 PGF2 was abolished, whereas 10 μm PGF2 and 0.05 μm U-46619 still caused substantial increases. These results suggest that low concentrations of PGF2 act via FP receptors to cause IP3-dependent Ca2+ release and store operated Ca2+ entry (SOCE). U-46619 and 10–100 μm PGF2 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.
    Original languageEnglish
    Pages (from-to)147 - 163
    Number of pages17
    JournalThe Journal of Physiology
    Issue number1
    Publication statusPublished - Feb 2006


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