Rectum has abnormal ion transport but normal cAMP-binding proteins in cystic fibrosis.
The luminal membranes of involved tissues in cystic fibrosis (CF) are relatively impermeable to Cl and the regulation of Cl transport by adenosine 3',5'-cyclic monophosphate (cAMP)-mediated hormones is abnormal. We investigated the human rectum as a putative model for CF. We compared in vivo transrectal potential difference (PD) in CF and in normal subjects in response to sequential perfusions with various test solutions. The base-line PD was different in normal (-35.5 +/- 4.0 mV; lumen negative; mean +/- SE; n = 9) and CF subjects (-23.4 +/- 3.1 mV; n = 6; P less than 0.025) and was eliminated by amiloride (10(-4) M) perfusion in both groups by 3 min. However, in response to a Cl-free solution with amiloride, all six CF subjects exhibit less of a change in PD (PD, -2.2 +/- 1.2 mV vs. -11.7 +/- 1.5 mV in 6 controls; P less than 0.01). Furthermore, normal subjects (n = 7) respond to a 5 mM theophylline + amiloride perfusion with an increase in lumen-negative PD, whereas, CF subjects (n = 6) show no increase in lumen-negative PD. Rectal biopsy specimens from four normal and four CF subjects exhibit similar (2- to 3-fold) increases in theophylline-induced cAMP content and have similar cAMP-binding proteins (CF, n = 3; control, n = 3). We conclude that the rectum is an involved epithelium in CF in which the aberration may lie at a point beyond the binding of cAMP to its protein kinase.
Goldstein
J L
JL
Department of Medicine, University of Illinois College of Medicine, Chicago.
Nash
N T
NT
al-Bazzaz
F
F
Layden
T J
TJ
Rao
M C
MC
D000328:Adult; D000584:Amiloride / Q000494:pharmacology; D001693:Biological Transport, Active; D002352:Carrier Proteins / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D002373:Cyclic AMP Receptor Protein; D003550:Cystic Fibrosis / Q000378:metabolism*; D005260:Female; D006801:Humans; D007477:Ions / Q000378:metabolism*; D008297:Male; D008970:Molecular Weight; D010539:Permeability; D012007:Rectum / Q000378:metabolism*; D013806:Theophylline / Q000494:pharmacology
D002352:Carrier Proteins; D002712:Chlorides; D002373:Cyclic AMP Receptor Protein; D007477:Ions; D000584:Amiloride; D013806:Theophylline