The application of platelet-activating factor (PAF) to the nasal mucosa of humans has been shown to increase histamine-induced hyper-reactivity. To test the hypothesis that PAF acts by increasing the reactivity of sensory nerve endings in the nasal mucosa to histamine, we examined PAF-stimulated rat trigeminal nerve ganglion cells. We found that relatively low concentrations of PAF (10(-12)-10(-9) M) induced increased histamine H1 receptor mRNA expression. This increase appeared as early as 1 h after PAF stimulation, peaked at 4 h, and disappeared after 24 h. The PAF receptor antagonist WEB2086 inhibited the increased expression of histamine H1 receptor mRNA induced by PAF, suggesting that the effects of PAF are mediated by specific receptors. This PAF effect was abolished by actinomycin D, suggesting that PAF induces de novo transcription of histamine H1 and/or PAF receptor mRNA. PAF may be important in the hyper-responsiveness of nasal mucosa exposed to histamine.