This study was undertaken to investigate the interactive effect of
histamine and
prostaglandin D(2) in nasal allergic symptoms in rats. The intranasal application of
histamine at doses lower than 10 mumol/site caused no
sneezing or nasal rubbing. In addition,
prostaglandin D(2) also showed no significant increase in these responses, even at a dose of 10 nmol/site. On the other hand, the simultaneous instillation of
histamine and
prostaglandin D(2) resulted in a 1000 times more potent effect in inducing nasal symptoms than the administration of
histamine alone. Thus,
prostaglandin D(2) enhanced the actions of
histamine in inducing
sneezing and nasal rubbing in a dose-dependent manner, and significant effects were observed at doses higher than 1 nmol/site. The responses induced by the simultaneous application of
histamine and
prostaglandin D(2) were inhibited by
chlorpheniramine,
cyproheptadine,
BW A868C and
ramatroban.
Chlorpheniramine and
cyproheptadine showed the dose-related inhibition of nasal symptoms induced by the combined administration of
histamine (10 nmol) and
prostaglandin D(2) (10 nmol), but the effect of
cyproheptadine was relatively weak compared with
chlorpheniramine. Moreover,
BW A868C and
ramatroban also showed the inhibition of nasal symptoms induced by the simultaneous administration of
histamine and
prostaglandin D(2) in a dose-dependent manner.
BW A868C was more potent in inhibiting the nasal symptoms than
ramatroban. These results clearly indicate that
prostaglandin D(2) showed a synergistic effect on
sneezing and nasal rubbing induced by
histamine in rats, and its effect occurred through both
prostaglandin D(2) and CRTH2 (
chemoattractant receptor-homologous molecule expressed on TH2 cells) receptors.