Responses of salivary acinar cells to intracellular alkalinization.

Responses of rat submandibular acini to intracellular alkalinization were investigated. Intracellular alkalinization was induced by addition of NH4Cl or methyl amines, or by prepulse with Na butyrate. Only partial recovery occurred following Na butyrate prepulse or methylated amine addition, but full recovery was observed following addition of NH4Cl. The latter recovery was DIDS and dimethylamiloride-insensitive but was inhibited by bumetanide or high [K+] and stimulated in Na(+)-free buffer and by ouabain. Acetylcholine stimulated recovery from NH4Cl- or Na butyrate pre-pulse-induced alkalinization and reduced the extent of alkalinization induced by methylated amines. Acetylcholine-stimulated recovery from NH4Cl-induced alkalinization was mimicked by substance P or ionomycin and was partially Ca(2+)-dependent. This stimulated recovery was bumetanide-insensitive but was partially sensitive to charybdotoxin. Taken together, these data indicate that in unstimulated cells, recovery from alkalinization induced by NH4Cl occurs by bumetanide-sensitive transport of the NH4+ ion, that DIDS-inhibitable anion transport contributes little to this recovery, and that acetylcholine and other Ca(2+)-elevating agents accelerate recovery from NH4Cl-induced alkaline challenge by a mechanism insensitive to bumetanide, DIDS, ouabain, and dimethylamiloride but sensitive to extracellular Ca2+ and to charybdotoxin. Partial recovery from alkaline challenge can also occur in the absence of NH4+ ions, and acetylcholine also stimulates this mode of recovery. Together, these data suggest that these cells have little intrinsic ability to recover from intracellular alkalinization and that the NH4+ ion may be a surrogate for K+ in at least two ion transport pathways.