Effect of an H1−receptor Antagonist, Fexofenadine Hydrochloride, on Substance P Secretion from Sensory Neurons in vitro
2009
Background and Objective Fexofenadine hydrochloride(FEX)is a second−generation histamineH1−receptor antagonist that is frequently used as an anti−allergic agent for the treatmentof allergic diseases, including allergic rhinitis(AR). Although it is generally acceptedthat the peripheral sensory neurons that innervate nasal mucosa contribute to the developmentof the clinical condition of AR, the effect of FEX on the function of sensory neurons isnot well defined. The present study was undertaken to determine the effect of FEX on sensoryneurons by investigating its effects on the dorsal root ganglion(DRG)cells from rats invitro.Methods DRG cells obtained from F344 rats on postnatal day 1 were stimulated with nervegrowth factor(NGF)in the presence of various concentrations of FEX. The effect of FEX onthe total number of neurites per DRG cell and on the percentage of DRG cells with outgrowingneurites was examined 24 h or 72 h after the start of culture, respectively. We also examinedsubstance P(SP)levels in 6 h−culture supernatants by ELISA.Results Addition of FEX to DRG cell cultures to a final concentration of 1000 ng/mL, twicethe therapeutic tissue levels, had hardly any effect on neurite growth from DRG cells,because the total number of neurites and the percentage of DRG cells with outgrowing neuritesobserved in the experimental cultures were nearly identical(not significant;p>0.05)tothe value in the control cultures stimulated with NGF alone. FEX inhibited SP productionfrom DRG cells in response to capsaicin stimulation. The minimum concentration of FEXthat caused significant inhibition was 500 ng/mL. The present results demonstrated that FEXinhibits the functions of sensory neurons, especially SP production without lethal effect onneurons.Conclusion These pharmacological actions in turn may contribute, in part, to the potentclinical efficacy of FEX against the neurogenic inflammation observed in AR.(Jpn Pharmacol Ther 2009;37:649−56)KEY WORDS Fexofenadine hydrochloride, Dorsal root ganglion cells, Substance P, Inhibition,in vitro
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