Altered sensitivity to amiloride in cystic fibrosis. Observations using cultured sweat glands.
1. Using cultured epithelia from sweat glands, derived from both cystic fibrosis and normal subjects, the relationship between amiloride concentration and the inhibition of electrogenic sodium transport was measured, under short circuit conditions. 2. The Kd for amiloride in cultures from normal subjects was 0.64 microM (n = 6) while in cultures derived from CF patients the value was 1.07 microM (n = 4). The values were significantly different (P less than 0.02, ANOVA). 3. In cultures from normal sweat glands, bathed in solutions free of permeable anions (chloride/bicarbonate), the Kd for amiloride rose to a value greater than found in CF tissues (2.3 microM). In CF epithelia subject to the same conditions the abnormally high value increased further, so that in solutions without permeable anions normal and CF cultures behaved similarly. 4. In cultures derived from normal and CF tissues lowering the sodium concentration to 10 mM also lowered the Kd for amiloride, however the shift was greater for CF cultures. 5. Several possible explanations for the results are discussed. The most probable is that the relatively more positive apical membrane potential in CF epithelia opposes the interaction of amiloride with the sodium channel, implying that complex formation is potential sensitive.
Cuthbert
A W
AW
Department of Pharmacology, University of Cambridge.
Brayden
D J
DJ
Dunne
A
A
Smyth
R L
RL
Wallwork
J
J
D000293:Adolescent; D000328:Adult; D000584:Amiloride / Q000378:metabolism / Q000494:pharmacology*; D002648:Child; D046508:Culture Techniques; D003550:Cystic Fibrosis / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D012964:Sodium / Q000378:metabolism; D013545:Sweat Glands / Q000187:drug effects / Q000378:metabolism*
D000584:Amiloride; D012964:Sodium