The effect of carbonic anhydrase inhibitors on the anionic composition of sheep's parotid saliva. With an appendix on uncatalysed carbon dioxide‐water kinetics by P. T. McTigue.

Abstract

SUMMARY1. The effects of the carbonic anhydrase inhibitors, acetazolamide, ethoxzolamide and benzolamide on the ionic composition of parotid saliva were studied in anaesthetized sheep with access to the parotid blood vessels.2. The inhibitors were infused directly into the arterial blood supply to the gland to give blood concentrations in the range 10-5 to 10-2 M.3. Mean anionic concentrations at basal flow rate before inhibitor infusion were, bicarbonate 98 m-mole/l., phosphate 15 m-mole/l. and chloride 26 m-mole/l. In the presence of inhibitors, bicarbonate concentration fell by 11 m-mole/ml. and phosphate-and chloride concentrations rose. Secreto-motor nerve stimulation increased bicarbonate concentration by 13 m-mole/l. before infusion of inhibitors and the concentrations of the other anions fell. The bicarbonate rise was abolished by the inhibitors and the fall in phosphate concentration was balanced by a rise in chloride concentration.4. These effects show that only a small component of the bicarbonate ion transfer system in the sheep parotid gland is sensitive to these inhibitors.5. The relationship of these findings to a new enzyme with carbonic anhydrase action isolated from the sheep's parotid gland is discussed.

The role of buffer anions and protons in secretion by the rabbit mandibular salivary gland.

“…6, Table 3), was as effective as has previously been reported with in vivo studies on salivary glands (Blair-West, Fernley, Nelson, Wintour & Wright, 1980;Young, Case, Conigrave & Novak, 1980). It is not surprising that enzyme inhibition had no…”

Local action of parathyroid hormone (1–34) and (1–84) at the parotid gland of sheep

“…2). The rises in phosphate concentration were not attributable to changes in salivary flow rate, earlier experiments having shown that salivary phosphate concentration varies inversely with salivary flow rate (Blair-West et al 1980). Intra-arterial infusion of PTH (1-84) increased salivary phosphate concentration despite the complete drainage of the venous effluent from the gland throughout the infusion period ( Fig.…”

“…Timed collections of venous blood were made for estimation of gland blood flow in all experiments, and all of the effluent was drained to prevent recirculation of infused PTH (1-84) in some experiments. Samples of saliva were collected from the cannulated parotid duct directly into syringes without obstruction or contact with air (Blair-West, Fernley, Nelson, Wintour & Wright, 1980). Chemical analysis was performed on a Technicon auto-analyser using standard methods.…”

Bicarbonate transport in sheep parotid secretory cells.

“…Intracellular HCO3-may be generated either from CO2 -by the action of carbonic anhydrase combined with basolateral extrusion of H+ -or by the uptake of HC03-across the basolateral membrane. In the parotid gland of the red kangaroo, Macropus rufus, carbonic anhydrase inhibitors largely block secretion of the HCO3--rich saliva (Beal, 1991) but in the sheep parotid they have a relatively small effect (Blair-West et al 1980) despite the high activity of the enzyme and the presence of two isoenzymes (Fernley, Wright & Coghlan, 1979). Of the mechanisms that might contribute to H+ extrusion in the sheep parotid, we can exclude the involvement of a H+-ATPase for the following reason.…”

“…This may explain why amiloride has little effect on fluid secretion in vivo (Wright et al 1986), but it does not necessarily indicate that Na+-H+ exchange provides the main driving force for HC03-accumulation. Indeed, other in vivo studies have shown that carbonic anhydrase inhibitors only reduce the saliva flow and HC03-output by about 40% (Blair-West, Fernley, Nelson, Wintour & Wright, 1980) suggesting that CO2 is not the only source of intracellular HC03-. Our recent studies of the HC03-dependence of intracellular Na+ concentration and cell volume indicate that a Na+-HCO3-cotransporter may be involved in the uptake of HC03-from the interstitium (Poronnik, Schumann & Cook, 1995).…”