Thromboxane sensitive (
TP)-receptors are widely distributed in the airways smooth muscle of various species. In man they mediate constrictor responses, not only to TxA2 but also to other
prostanoids such as
PGD2 and
PGF2 alpha. The evidence for the involvement of these
TP-receptors in human
asthma is equivocal; however, the recent development of potent, selective
TP-receptor blocking drugs such as
GR32191 has provided the opportunity to answer this question.
GR32191 (80mg p.o.) caused a marked inhibition of
PGD2 but not
methacholine-induced
bronchospasm in asthmatic subjects, and also caused a modest reduction in
allergen-induced
bronchospasm. However, it had no inhibitory effect against the bronchoconstriction resulting from inhaled PAF or from exercise. Finally,
GR32191 was tested in moderate to severe asthmatics for its ability to reduce symptom scores. At a dose of 40mg four times a day for three weeks,
GR32191 had no effect upon morning or evening peak expiratory flow rates, on subjective symptom score, on
bronchodilator usage or on occurrence of nocturnal dyspnoea. These results do not support a key role for
prostanoids acting through
TP-receptors in the aetiology of
asthma.