Regulation of changes in cytosolic Ca2+ and Na+ concentrations in rat submandibular gland acini exposed to carbachol and ATP.
The relationship between cytosolic concentrations of Ca2+ (Ca2i) and Na+ (Na+i) were studied in preparations of rat submandibular and pancreatic acini loaded with the Ca(2+)-sensitive dye Fura-2 or the Na(+)-sensitive dye SBFI. Pancreatic acini showed no changes in Na+i during either transient or persistent changes in Ca2+i. Increases in Ca2+i produced by exposure of submandibular gland acini to carbachol, a muscarinic cholinergic agonist, were followed by an increase in Na+i after a delay of 5-10 s. When Ca2+ stores were mobilized without Ca2+ influx Na+i also increased, but in acini loaded with BAPTA, a nonfluorescent Ca2+ chelator, the transient increase in Ca2+ caused by mobilization of stored Ca2+ was virtually abolished, as was the increase in Na+i. In the presence of inomycin, increases in Ca2+i were followed by increases in Na+i. Ca(2+)-dependent increases in Na+i were abolished in Na(+)-free buffer and by the presence of furosemide, a blocker of Na(+)-K(+)-2Cl- cotransport. In other studies, extracellular ATP (ATPo) produced an increase in Ca2+i and Na+i. The steady-state increase in Ca(i)2+ was reduced by increasing extracellular Na+ concentrations (Na+o in dose-dependent fashion (IC50 = 16.4 +/- 4.7 mM Na+). Likewise, increasing Na+o reduced ATPo-stimulated 45Ca2+ uptake at steady state (IC50 = 15.8 +/- 9.2 mM Na+). Changing Na+o had no effect on carbachol-stimulated increases in Ca2+i. We conclude that, in rat submandibular gland acini, ATPo promotes an increase in Ca2+i and Na+i via a common influx pathway and that, under physiologic conditions, Na+ significantly limits the ATPo-stimulated increase in Ca2+i. In the presence of carbachol, however, Na+i rises in Ca2+i-dependent fashion in submandibular gland acini via stimulation of Na(+)-K(+)-2Cl- cotransport.
Hurley
T W
TW
Department of Child Health, University of Missouri-Columbia, School of Medicine 65212, USA.
Ryan
M P
MP
Moore
W C
WC
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001572:Benzofurans / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology*; D002614:Chelating Agents / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D004988:Ethers, Cyclic / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D016257:Fura-2 / Q000378:metabolism; D005665:Furosemide / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D010179:Pancreas / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism*; D013363:Submandibular Gland / Q000378:metabolism*
D001572:Benzofurans; D002614:Chelating Agents; D004988:Ethers, Cyclic; D005456:Fluorescent Dyes; C061665:sodium-binding benzofuran isophthalate; D004533:Egtazic Acid; D015759:Ionomycin; D001285:Atropine; D005665:Furosemide; D000255:Adenosine Triphosphate; D002217:Carbachol; D012964:Sodium; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium; D016257:Fura-2