Cl- fluxes related to fluid secretion by the rat parotid: involvement of Cl(-)-HCO3- exchange.
Muscarinic-induced 36Cl- and 86Rb+ (K+ substitute) fluxes were studied in rat parotid acini. Stimulation resulted in a rapid [half time (t1/2) less than 30 s] decrease in both Cl- and Rb+ content (approximately 50 and 30%, respectively) followed by a slower partial recovery (t1/2 approximately 3-4 min) to approximately 80% of resting levels for both ions. Cl- loss was inhibited by the venom of Leiurus quinquestriatus, which contains the maxi-K+ channel blocker charybdotoxin. Cl- recovery was blunted in the presence of bumetanide, an inhibitor of Na(+)-K(+)-Cl- cotransport, or on HCO3- removal and was completely blocked in the presence of bumetanide and 4,4' diisothiocyanostilbene-2,2' disulfonic acid (DIDS), an inhibitor of Cl(-)-HCO3- exchange. In HCO3(-)-containing medium a rapid (t1/2 less than 1 min), DIDS-inhibitable cytoplasmic alkalinization (approximately 0.4 pH unit) was observed in acini switched to a Cl(-)-free solution. This alkalinization was not seen in HCO3(-)-free medium but persisted in the absence of Na+, consistent with the presence of a potent Na(+)-independent Cl(-)-HCO3- exchanger. Kinetic studies indicated that the half-maximal effect of this exchanger for extracellular Cl- was approximately 18 mM. These results are consistent with the hypothesis that secretagogue-induced KCl loss by salivary acinar cells occurs via electrically coupled K+ and Cl- channels. In addition, they provide strong evidence that Cl- entry into, and thus fluid secretion by, these cells is mediated by both Cl(-)-HCO3- exchange and Na(+)-K(+)-Cl- cotransport.
Melvin
J E
JE
Department of Dental Research, University of Rochester, New York 14642.
Turner
R J
RJ
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology; D002034:Bumetanide / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D027963:Chloride-Bicarbonate Antiporters; D002712:Chlorides / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D010306:Parotid Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D012413:Rubidium / Q000378:metabolism
D001639:Bicarbonates; D002352:Carrier Proteins; D027963:Chloride-Bicarbonate Antiporters; D002712:Chlorides; D002034:Bumetanide; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D002217:Carbachol; D012413:Rubidium; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid