## Abstract

Salivary glands form their secretions by first elaborating an isotonic plasma-like primary fluid in the endpieces and then modifying the composition of this secretion during its passage along the gland duct system. We have studied the role of extracellular anions in both primary secretion and ductal modification with a recently developed technique for isolation and perfusion of the rabbit mandibular gland. Neither of the major extracellular anions (Cl<latex>$^-$</latex> or HCO<latex>$^-_3$</latex>) is essential for primary fluid secretion. HCO<latex>$^-_3$</latex> can be removed altogether and replaced with Cl<latex>$^-$</latex> without diminution in secretory rate, provided that extracellular pH is maintained at 7.4, and its replacement with acetate actually enhances secretion. Complete replacement of Cl<latex>$^-$</latex> with Br<latex>$^-$</latex> also enhances secretion and replacement with I<latex>$^-$</latex>, NO<latex>$^-_3$</latex>, CH<latex>$_3$</latex>SO<latex>$^-_4$</latex> or isethionate supports secretion but at progressively diminishing rates. Our data do not yet allow us to distinguish between an electroneutral Na<latex>$^+$</latex>-Cl<latex>$^-$</latex> cotransport model or a double countertransport (Na<latex>$^+$</latex>-H<latex>$^+$</latex> plus Cl<latex>$^-$</latex>-HCO<latex>$^-_3$</latex>) model as the basis of primary salivary secretion, or to propose any more suitable alternative model. With respect to ductal modification of the primary saliva, HCO<latex>$^-_3$</latex> omission inhibits ductal Na<latex>$^+$</latex> absorption (i.e. salivary Na<latex>$^+$</latex> concentration rises). This inhibition is probably related to an effect of pH on the postulated Na<latex>$^+$</latex>-H<latex>$^+$</latex> exchange mechanism in the luminal duct membrane since it can also be induced by lowering perfusate pH, and reversed by substitution of perfusate HCO<latex>$^-_3$</latex> with acetate (which enters saliva) but not HEPES (which does not enter the saliva). Substitution of perfusate Cl<latex>$^-$</latex> with other anions seems not to inhibit ductal Na<latex>$^+$</latex> and K<latex>$^+$</latex> transport markedly. Salivary glands form their secretions by first elaborating an isotonic plasma-like primary fluid in the endpieces and then modifying the composition of this secretion during its passage along the gland duct system. We have studied the role of extracellular anions in both primary secretion and ductal modification with a recently developed technique for isolation and perfusion of the rabbit mandibular gland. Neither of the major extracellular anions (Cl<latex>$^-$</latex> or HCO<latex>$^-_3$</latex>) is essential for primary fluid secretion. HCO<latex>$^-_3$</latex> can be removed altogether and replaced with Cl<latex>$^-$</latex> without diminution in secretory rate, provided that extracellular pH is maintained at 7.4, and its replacement with acetate actually enhances secretion. Complete replacement of Cl<latex>$^-$</latex> with Br<latex>$^-$</latex> also enhances secretion and replacement with I<latex>$^-$</latex>, NO<latex>$^-_3$</latex>, CH<latex>$_3$</latex>SO<latex>$^-_4$</latex> or isethionate supports secretion but at progressively diminishing rates. Our data do not yet allow us to distinguish between an electroneutral Na<latex>$^+$</latex>-Cl<latex>$^-$</latex> cotransport model or a double countertransport (Na<latex>$^+$</latex>-H<latex>$^+$</latex> plus Cl<latex>$^-$</latex>-HCO<latex>$^-_3$</latex>) model as the basis of primary salivary secretion, or to propose any more suitable alternative model. With respect to ductal modification of the primary saliva, HCO<latex>$^-_3$</latex> omission inhibits ductal Na<latex>$^+$</latex> absorption (i.e. salivary Na<latex>$^+$</latex> concentration rises). This inhibition is probably related to an effect of pH on the postulated Na<latex>$^+$</latex>-H<latex>$^+$</latex> exchange mechanism in the luminal duct membrane since it can also be induced by lowering perfusate pH, and reversed by substitution of perfusate HCO<latex>$^-_3$</latex> with acetate (which enters saliva) but not HEPES (which does not enter the saliva). Substitution of perfusate Cl<latex>$^-$</latex> with other anions seems not to inhibit ductal Na<latex>$^+$</latex> and K<latex>$^+$</latex> transport markedly.