Role of the 5-HT receptor in neurogenic inflammation in Fisher 344 rat airways.

The increased plasma protein extravasation in the airways of Fisher 344 rats upon stimulation of sensory nerves is in part due to the degranulation of mast cells. In this study, we examined the role of 5-HT and histamine receptors in the capsaicin-induced increase in plasma protein extravasation in Fisher 344 rat airways, using Evans blue as an intravascular marker. We found that only 5-HT2 receptor agonists increased baseline plasma protein extravasation. Furthermore, the 5-HT2 receptor antagonist ketanserin reduced the capsaicin-induced increase in plasma protein extravasation. Combining ketanserin with the tachykinin NK1 receptor antagonist (+/-)-RP 67,580 ((3alphaR,7alphaR)-(7,7-diphenyl-2(1-imino-2-(2-methoxyph enylethyl)-perhydraisoinositol-4-one))) abolished the neurogenic increase in plasma protein extravasation. Finally, using selective receptor agonists and antagonists, we demonstrated that there was no modulation of the capsaicin-induced rise in plasma protein extravasation by stimulation of either histamine receptors or 5-HT1, 5-HT3 and 5-HT4 receptors. We conclude that, in the airways of Fisher 344 rats, the neurogenic increase in plasma protein extravasation is caused by activation of both tachykinin NK1 receptors and 5-HT2 receptors.