Role of sodium in mediator release from human basophils.
We studied the effect of extracellular sodium concentration on histamine release (HR) from human basophils initiated by immunologic and nonimmunologic stimuli. We found that lowering extracellular sodium markedly enhances HR induced by an immunologic stimulus from these cells. In buffer in which sodium had been replaced with univalent ions of strong bases, enhancement of HR increased as extracellular sodium decreased. Enhancement was the result of increased duration of release. When sucrose was used for replacement of sodium, we also observed that enhancement of HR increased as extracellular sodium decreased, but there was some lessening of enhancement at [Na+]e between 5 and 10 mmol/L. Ouabain, which is an inhibitor of the Na+/K+ adenosine triphosphatase, and bumetanide and furosemide, which are inhibitors of Cl(-)-dependent Na(+)-K+ cotransport, caused small increases in enhancement of HR by sodium-deficient buffers; 4,4'-diisothiocyanostilbene-2-2'-disulfonic acid, an anion transport inhibitor, caused some inhibition of enhancement of HR. Analogues of amiloride, such as 5-(N-N-hexamethylene) amiloride (HMA) and 5-(N-4-chlorobenzyl)-2'-4'dimethylbenzamil (CBDMB), inhibit Na+/H+ exchange, Na+/Ca++ exchange, and Na+ channels. Interestingly, at higher doses, HMA and CBDMB caused marked enhancement of HR in both normal and sodium-deficient buffers. These results suggest that several cellular regulatory mechanisms potentially are important for normal basophil secretion. The most likely are pH regulatory mechanisms that include Na+/H+ exchange and anion exchangers that transport alkaline equivalents. Our findings enhancement of basophil HR by HMA and CBDMB is particularly noteworthy in light of the recent interest in use of amiloride by inhalation for therapy of lung disease in patients with cystic fibrosis.
Smith
T F
TF
Division of Allergy, Immunology, Emory University School of Medicine, Atlanta, Ga.
Sanchez-Legrand
F
F
McKean
L P
LP
Kutner
M H
MH
Cragoe
E J
EJ
Eaton
D C
DC
D001491:Basophils / Q000276:immunology / Q000378:metabolism*; D002352:Carrier Proteins / Q000502:physiology; D002712:Chlorides / Q000502:physiology; D005110:Extracellular Space / Q000378:metabolism; D006636:Histamine Release; D006801:Humans; D009994:Osmolar Concentration; D012964:Sodium / Q000378:metabolism / Q000502:physiology*; D019831:Sodium-Calcium Exchanger; D017923:Sodium-Hydrogen Exchangers; D028021:Sodium-Potassium-Chloride Symporters
D002352:Carrier Proteins; D002712:Chlorides; D019831:Sodium-Calcium Exchanger; D017923:Sodium-Hydrogen Exchangers; D028021:Sodium-Potassium-Chloride Symporters; D012964:Sodium