Evidence that neuroepithelial endocrine cells control the spontaneous tonein guinea pig tracheal preparations

The hypothesis that neuroepithelial endocrine (NEE) cells control spontaneo us tone in isolated guinea pig tracheal preparations was examined. Epitheli um-denuded preparations were unable to develop a normal oscillating tone in 12% oxygen (corresponding to systemic arterial oxygen levels) and, instead , developed a strong, smooth tone, similar to the "classic" tone in 94% oxy gen. Inhibition of the hydrogen peroxide-producing NADPH oxidase in the NEE cells by 20 mu M diphenyleneiodonium chloride transformed, in intact prepa rations in 94% oxygen, the tone from a strong, smooth type to an oscillatin g tone of considerably less force. Similar experiments in denuded preparati ons showed no change of tone and no oscillations. After pretreatment with t he catalase inhibitor 3-amino-1,2,4-triazole (1 mM), addition of 2 mM hydro gen peroxide to intact preparations displaying the oscillating tone caused a transformation to a strong, smooth type. These findings support the hypot hesis that the spontaneous tone in this preparation is largely controlled b y the oxygen-sensing NEE cells. For the first time, previous findings on is olated cells can be linked to effects in intact tissue preparations. The re sults also suggest that the regulation by the NEE cells involves the releas e of powerful relaxing and contracting factors from the epithelium.