chial smooth muscle Vascular smooth muscle Dendritic cells Platelets CNS Biological effects Chemotaxis and activation of Th2 lymphocytes, eosinophils and basophils CNS effects unknown Bronchodilatation Vasodilatation Suppression of cytokine production by dendritic cells leading to polarization of Th2 cells Inhibition of platelet aggregation Likely involvement in CNS effects e.g. sleep and pain cognition Abbreviations: CRTH2, chemoattractant receptor-homologous molecule expressed on Th2 cells; PGD2, prostaglandin D2; Th2 cell, T helper type 2 cell. Activation of DP1 contributes to blood flow changes during allergic responses It has been recognized for some time that PGD2 has the potential to mediate the pathological blood flow changes observed in allergic diseases. In the case of allergic rhinitis, engorgement of the vasculature in the nose contributes to congestion, a troublesome symptom, which is largely resistant to the action of H1 antagonists. The mechanisms of the vascular changes in the mucosa of patients allergic rhinitis is complex but is thought to involve the direct actions 
of mediators on both the vasculature and neuronal reflexes. Blood flow changes contribute to the swelling of the nasal mucosa causing congestion and enhanced leakage of plasma protein, which contributes to nasal secretions. The importance of blood flow changes to the signs and symptoms of rhinitis is evident based on the effectiveness of vasoconstrictors such as pseudoephedrine to reduce `stuffiness’. In human volunteers intravenous administration of PGD2 has been shown to produce nasal congestion associated with intense facial flushing but interestingly, no overt effects on systemic blood pressure or lung function. Congestion has also been observed after insufflation of PGD2 in human subjects and it is more effective in PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19804355 this respect than either histamine or bradykinin 153 S191S199 S194 Role of DP1 and CRTH2 in allergic inflammation R Pettipher 1990). The ability of PGD2 to induce nasal air flow resistance is blocked by the vasoconstrictor oxymetazoline highlighting the importance of a vascular event in mediating this response. Production of PGD2 in response to allergen in pigs has been proposed to mediate a long-lasting component of airway vasodilatation resistant to antihistamines. This conclusion is based on the ability of PGD2 to mimic the long-lasting airways vasodilatation induced by allergen and the inhibitory effect of the cyclooxygenase inhibitor diclofenac on allergeninduced blood flow changes. The vasoactive effect of PGD2 appears to be more marked in the nose than the lower airways and so be more relevant to allergic rhinitis than asthma. The availability of selective DP1 agonists and antagonists have shown that vasorelaxation of vascular smooth muscle in response to PGD2 is DP1-mediated and the hypotensive effect of PGD2 is inhibited by BW A868C which suggests that the vascular effects described above are likely to be mediated by DP1. Indeed, the selective DP1 GW 501516 web agonist BW245C-induced headache, nasal stuffiness and facial flushing when infused into human volunteers. Most recently it has been shown that increased nasal airway resistance induced by intranasal instillation of PGD2 in conscious sheep is completely inhibited by a selective DP1 antagonist. While there are no reports on the effects of selective DP1 antagonists on vascular engorgement or congestion in clinical allergy it is of interest that the DP1 antagonist MK0524 has been reported to