Mast cell exocytosis can be triggered by ammonium chloride with just a cytosolic alkalinization and no calcium increase.
A human mast cell line (HMC-1) has been used to study the effect of cytosolic alkaline pH in exocytosis. Compound 48/80, concanavalin A, and thapsigargin do not induce histamine release in HMC-1 cells. Although thapsigargin does not activate histamine release, it does show a large increase in cytosolic Ca(2+), and no change in cytosolic pH. However, when HMC-1 cells were activated with ionomycin, a significant histamine release takes place, and this effect is higher in the presence of thapsigargin. Both drugs show an additive effect on cytosolic Ca(2+) levels. Ammonium chloride (NH(4)Cl) does activate cytosolic alkalinization and histamine release, with no increase in cytosolic Ca(2+). NH(4)Cl does block the release of internal Ca(2+) by thapsigargin, not by ionomycin, and decreases Ca(2+) influx stimulated by these drugs. Under conditions in which the alkalinization induced by NH(4)Cl is blocked by acidification with sodium propionate, histamine release is inhibited. The release of histamine is also observed when NH(4)Cl is added after propionate addition, regardless of the final pH value attained. Our results show that a shift in pH alkaline values, even with final pH below 7.2 is enough to activate histamine release. A shift to less acidic values is a sufficient signal to activate the cells.
Pernas-Sueiras
O
O
Departamento de Farmacología, Facultad de Veterinaria, USC, Lugo, Spain.
Alfonso
A
A
Vieytes
M R
MR
Botana
L M
LM
D000643:Ammonium Chloride / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D003600:Cytosol / Q000187:drug effects* / Q000378:metabolism*; D005089:Exocytosis / Q000187:drug effects*; D006632:Histamine / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015759:Ionomycin / Q000494:pharmacology; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism*; D019284:Thapsigargin / Q000494:pharmacology
D000643:Ammonium Chloride; D015759:Ionomycin; D019284:Thapsigargin; D006632:Histamine; D002118:Calcium