Effect of NPPB on chloride (Cl-) transport in distal colon of potassium (K+) adapted rats.
Secondary hyperaldosteronism enhances the rate of K secretion in distal colon, at least in part, through the stimulation of Na(+)-K(+)-Cl- cotransport across the basolateral membrane. To maintain a constant intracellular Cl- activity an increase in Cl- transport out of the cell must be assumed. We explored, under amiloride 10(-4) M and short circuited conditions, conductive pathways for Cl- exit in the distal colon of K(+)-adapted rats by means of a putative Cl- channel blocker, NPPB (5-nitro-2(3-phenyl-propylamino-benzoate. Results prior to NPPB showed an increase in JClms after K+ loading from 5.84 +/- 0.66 to 8.33 +/- 0.86 and JClsm from 4.77 +/- 0.55 to 8.16 +/- 0.96 microEq h-1 cm-2 (P < 0.001), when compared with controls. Net fluxes were not different between groups. Luminal NPPB in K+ adaptation resulted in a decrease of JClsm, from 7.85 +/- 1.5 to 6.69 +/- 1.5 microEq h-1 cm-2 (P < 0.05). There were no changes in both unidirectional Cl- fluxes in controls under luminal NPPB and in potential difference (V) and short-circuit current (Isc) under any condition. Finally, K+ adaptation resulted in an increase of luminal cyclic AMP (cAMP) concentration (0.09 +/- 0.02 to 0.20 +/- 0.03 pmol 100 microliters -1, P < 0.005), when compared with control rats. The data may suggest a transcellular recycling of Cl- and an activated NPPB inhibitable serosal to mucosal Cl- pathway on luminal membrane in the K+ adapted state, possibly mediated by an increase in cAMP production.
Veron
D
D
Instituto de Investigaciones Médicas Alfredo Lanari, University of Buenos Aires, Argentina.
Martin
R S
RS
Escobar
E
E
Tufaro
D
D
Visconti
P
P
Tezon
J G
JG
Arrizurieta
E E
EE
D000222:Adaptation, Physiological; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002463:Cell Membrane Permeability; D018118:Chloride Channels / Q000187:drug effects / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D009579:Nitrobenzoates / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D018118:Chloride Channels; D002712:Chlorides; D009579:Nitrobenzoates; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D000584:Amiloride; D000242:Cyclic AMP; D011188:Potassium