Ion transport abnormalities in rectal suction biopsies from children with cystic fibrosis.
Abnormalities in transepithelial electrolyte transport in cystic fibrosis rectum were analyzed by short-circuit current measurements on 11 control subjects and 11 subjects with cystic fibrosis in a modified Ussing chamber. As judged by the amiloride-sensitive component of the short-circuit current, electrogenic sodium absorption appeared unmodified in cystic fibrosis. In contrast, the short-circuit current response to specific stimuli of both cyclic adenosine monophosphate (cAMP)- and calcium-mediated chloride secretion was drastically altered in all of the cystic fibrosis biopsy specimens examined. Stimulation of the cAMP pathway by 8-bromo cAMP or forskolin resulted in a sustained increase in short-circuit current in control tissues (+ 2.51 +/- 0.63 microA/cm2) but in a slight change in the opposite direction in cystic fibrosis (-0.56 +/- 0.49 microA/cm2; P less than 0.05). Carbachol, a calcium-linked secretagogue, provoked a transient increase in short-circuit current in all of the control tissues (peak response, + 26.69 +/- 3.63 microA/cm2) but a transient change in the opposite direction in 6 of 11 cystic fibrosis tissues (-12.46 +/- 4.64 microA/cm2; P less than 0.05). In 2 of 11 patients with cystic fibrosis, however, a significant but subnormal and transient increase in short-circuit current was observed (+ 2.62 +/- 0.04 microA/cm2; P less than 0.05), whereas in 3 of 11 patients with cystic fibrosis a transient change in the opposite direction (-9.83 +/- 2.20 microA/cm2; P less than 0.05) was followed by a small and transient increase (+ 2.89 +/- 0.83 microA/cm2; P less than 0.05). Using the calcium-mediated secretory response therefore, patients with cystic fibrosis could be divided into two categories: a major population showing defective anion secretion but active cation secretion and a subclass (including three siblings) showing residual but subnormal anion secretion. The easy accessibility of rectal samples and the inversed direction of the cAMP- or calcium-provoked short-circuit current is of considerable advantage in the diagnosis of cystic fibrosis.
Veeze
H J
HJ
Department of Pediatrics, University Hospital Rotterdam/Sophia Children's Hospital, The Netherlands.
Sinaasappel
M
M
Bijman
J
J
Bouquet
J
J
de Jonge
H R
HR
D000293:Adolescent; D001693:Biological Transport, Active; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D002712:Chlorides / Q000378:metabolism*; D003550:Cystic Fibrosis / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology; D004594:Electrophysiology; D006801:Humans; D007223:Infant; D012007:Rectum / Q000378:metabolism / Q000473:pathology*; D012964:Sodium / Q000378:metabolism*
D002712:Chlorides; D012964:Sodium