HCO3- potentiates the cAMP-dependent secretory response of the human distal colon through a DIDS-sensitive pathway.
We used the Ussing short-circuit technique to investigate the role of HCO3- in the adenosine 3',5'-cyclic monophosphate (cAMP)-dependent secretory response of the human distal colon. In HCO3(-)-free 4-(2-hydroxyethyl)-1-piperazineethanesulphonic acid (HEPES)-Ringer's, forskolin (10 mumol l-1 mucosal and serosal) evoked a sustained increase in short-circuit current (Isc) (delta Isc = 24 +/- 3 microA cm-2, n = 57). However, this was only 25% of the forskolin-stimulated Isc response in HCO3(-)-Ringer's (delta Isc = 84 +/- 8 microA cm-2, n = 57). The reduced response to forskolin in HCO3(-)-free HEPES-Ringer's was not due to inhibition of the secretory mechanism by HEPES, as replacing HCO3- with a different buffer, N-tris[hydroxymethyl)methyl-2-aminoethanesulphonic acid (TES), had a similar effect and inclusion of HEPES in the HCO3(-)-Ringer's did not reduce the secretory response. Similarly, it was not due to an indirect modulation of electrogenic Cl- secretion, as the forskolin-stimulated bumetanide-sensitive Isc was comparable in the two Ringer's. Rather it was due to the activation of a HCO3(-)-dependent Isc which was inhibited by serosal 4,4'-diisothiocyano-stilbene-2,2'-disulphonate (DIDS). This DIDS-sensitive Isc was not inhibited by acetazolamide, but it was inhibited by the replacement of bathing solution Cl- with gluconate, suggesting a role for a Na(+)-dependent Cl-/HCO3- exchanger in the cAMP-dependent secretory response of the human distal colon.
Taylor
J
J
Department of Physiology, School of Medical Sciences, University of Otago, P.O. Box 913, Dunedin, New Zealand.
Hamilton
K L
KL
Butt
A G
AG
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology*; D001639:Bicarbonates / Q000494:pharmacology*; D002021:Buffers; D002034:Bumetanide / Q000494:pharmacology; D002256:Carbonic Anhydrases / Q000502:physiology; D002712:Chlorides / Q000378:metabolism / Q000502:physiology; D005576:Colforsin / Q000494:pharmacology; D003106:Colon / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D000242:Cyclic AMP / Q000502:physiology*; D004594:Electrophysiology; D006531:HEPES / Q000494:pharmacology; D006801:Humans; D007552:Isotonic Solutions / Q000494:pharmacology; D000077331:Ringer's Solution; D014325:Tromethamine / Q000031:analogs & derivatives* / Q000494:pharmacology
D001639:Bicarbonates; D002021:Buffers; D002712:Chlorides; D007552:Isotonic Solutions; D014325:Tromethamine; D002034:Bumetanide; D005576:Colforsin; C004551:TES; D000077331:Ringer's Solution; D000242:Cyclic AMP; D002256:Carbonic Anhydrases; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D006531:HEPES