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 methylamines, 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 Ca²⁺-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 Ca²⁺-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. © 1994 wiley-Liss, Inc.