Prostaglandin D(2) (
PGD(2)), released through mast cell activation, is used as a non-invasive
biomarker in patients with
asthma. Since
PGD(2) can elicit opposing effects on airway tone via activation of the
PGD(2) receptors DP(1) and DP(2) as well as the
thromboxane receptor TP, the aim of this study was to characterize the receptors that are activated by
PGD(2) in the guinea pig lung parenchyma.
PGD(2) and the
thromboxane analog
U46619 induced concentration-dependent contractions.
U46619 was more potent and caused stronger effect than
PGD(2). The specific
TP receptor antagonist
SQ-29548 and the combined TP and DP(2) receptor antagonist BAYu3405 concentration-dependently shifted the curves for both agonists to the right. The DP(1) receptor agonist BW245 induced a weak relaxation at high concentrations, whereas the DP(1) receptor antagonist
BWA868C did not affect the
PGD(2) induced contractions. The specific DP(2) receptor agonist 13,14-dihydro-15-keto-PGD(2) showed neither contractile nor relaxant effect in the parenchyma. Furthermore, studies in precision-cut lung slices specified that airways as well as pulmonary arteries and veins contracted to both
PGD(2) and
U46619. When the lung parenchyma from
ovalbumin sensitized guinea pigs were exposed to
ovalbumin, both
thromboxane B(2) and
PGD(2) were released.
Ovalbumin also induced maximal contractions at similar level as
PGD(2) in the parenchyma, which was partly reduced by
SQ-29548. These data show that
PGD(2) should be recognized as a
TP receptor agonist in the peripheral lung inducing contraction on airways, arteries and veins. Therefore, a
TP receptor antagonist can be useful in combination treatment of allergic responses in
asthma.