The mechanisms by which prostaglandin F_2α (PGF_2α) induces increases in [Ca²⁺]_i and activates smooth muscle contraction are unclear. We have studied the effects of PGF_2α on contraction and [Ca²⁺]_i in the rat pulmonary artery using fura PE-3 AM-loaded isolated intrapulmonary arteries.

Rats were humanely killed by cervical dislocation.

Low concentrations of PGF_2α (10-100 nM) caused a transient increase in [Ca²⁺]_i followed by a sustained plateau but did not induce contraction. Further increases in [PGF_2α] (3-30 µM) caused a dose-dependent increase in tension but no further increase in [Ca²⁺]_i. In nominally Ca²⁺-free solution, the transient component of the Ca²⁺ response was still present but the [Ca²⁺]_i plateau was abolished. Even without further elevation in [Ca²⁺]_i, tension still increased in a dose-dependent manner. Tension dose-response curves show that V_max in Ca²⁺-free physiological salt solution (PSS) was 70 % of that in Ca²⁺-containing PSS, i.e significantly smaller (P < 0.05, Student’s paired t test). However, EC₅₀ values were similar: 3.4 ± 0.7 µM (n = 7, mean ± S.E.M.) in Ca²⁺-containing PSS and 5.1 ± 0.8 µM (n = 7) in Ca²⁺-free PSS. The [Ca²⁺]_i transient and plateau could be reproduced with the selective PGF_2α receptor (FP) receptor agonist fluprostenol. However, no increase in tension was caused by fluprostenol even at 10 µM. The [Ca²⁺]_i transient and plateau evoked by both fluprostenol and PGF_2α could be inhibited with the selective FP receptor antagonist AL-8810, or with thapsigargin. In contrast the thromboxane A₂ analogue U-46619 caused a sustained dose-dependent increase in [Ca²⁺]_i and tension. The selective thromboxane A₂ receptor (TP) antagonist SQ29584 completely blocks increases in [Ca²⁺]_i and tension caused by U-46619, and abolished the rise in tension, but not the [Ca²⁺]_i response, induced by PGF_2α.

These results suggest that PGF_2α elevates [Ca²⁺]_i via FP receptor-induced Ca²⁺ release from intracellular stores with subsequent capacitative calcium entry. However, this is not sufficient to cause contraction, which requires simultaneous activation of TP receptors.

This work was supported by the Wellcome Trust.