Transforming Growth Factor-b1 (TGF-b1) is a critical mediator of normal lung development, but also involved in many respiratory dysfunctions. Amongst other effects, there is growing evidence concerning the impact of TGF-b1 as a mediator of transepithelial ion transport. In our present study we investigated the effect of TGF-b1 on epithelial Na+-transport in dissected rabbit tracheas by Ussing chamber measurements. In native rabbit tracheal epithelium we found that short time exposure of 10 ng/ml TGF-b1 (< 30 minutes) on the apical side of the preparations deacerased short-circuit current (Isc) from 69,98+6,85 to 62,7+6,8 mA/cm2 (n=8); this slight decrease of Isc was accompanied by a more pronounced decrease of the amilorid-sensitive part (Iami) of the current. Iami was 27,75+3,87 mA/cm2 in control experiments (n=8), and 16,75+2,24 mA/cm2 after TGF-b1 exposure (n=8). The quick appearance of the effect argues for a transcription-independent mechanism. Taken together, our data indicate that TGF-b1 decreases transepithelial Na+-absorption in rabbit tracheal epithelium in a short time manner which may involve novel, non-transcriptional signalling pathways. Supported by DFG, FR2124