CAMBRIDGE. parotid salivary flow and composition in the sheep. The possibility that the. SALIVARY FLOW AND COMPOSITION IN CONSCIOUS SHEEP.

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1 Quarterly Journal of Experimental Phy8iology (1975), 60, THE EFFECT OF POTASSIUM CHLORIDE INFUSION ON PAROTID SALIVARY FLOW AND COMPOSITION IN CONSCIOUS SHEEP. By A. M. BEAL,* 0. E. BUDTZ-OLSEN and R. C. CLAK. From the Sir William Macgregor School of Physiology, University of Queensland, St. Lucia, Queensland, Australia 4067 and the Department of Physiology, A.R.C. Institute of Animal Physiology, Babraham, Cambridge. (Received for publication 8th October 1974) (Revi8ed ver8ion 6th January 1975) The composition and flow of parotid saliva in conscious sheep was measured before, during and after the intravenous infusion of 0 43 M-KCl or 043 M-NaCl at 2 ml./min for 2 hr. The salivary flow rate was depressed during the infusion of potassium chloride into both intact sheep and adrenalectomized sheep. As the salivary flow was unchanged by sodium chloride infusion it was concluded that the potassium ion was responsible for the decrease in flow and that this effect was not mediated through any of the adrenal hormones. The highly significant negative correlation between plasma potassium concentration and salivary flow throughout all potassium infusions indicated that the extent to which the salivary flow was depressed varied with the degree of hyperkalaemia. Except for situations where mineralocorticoid levels were likely to be elevated the concentrations of sodium and potassium in the saliva were positively correlated with the plasma concentrations of these ions. The salivary bicarbonate concentration was positively correlated with the salivary flow whereas the phosphate concentration of the saliva was negatively related to flow. The chloride concentration of the saliva was negatively correlated with salivary flow during all potassium chloride infusions. The injection of potassium chloride into the arterial supply of the submaxillary gland of the cat has been found to cause a response varying from no effect on salivary flow to marked stimulation of secretion [Feldberg and Guimarais, 1936]. Subsequently the intravenous infusion of potassium chloride was reported to increase the rate of saliva production by the parotid gland of the dog [Langley, Gunthorpe and Beall, 1958]. However, while investigating the amount of potassium secreted in the parotid saliva of sheep in response to the infusion of potassium chloride, Beal, Budtz-Olsen, Clark, Cross and French [1973] observed that salivary flow was depressed during and after this treatment. From these observations the question arises whether the fall in salivary flow during potassium infusion in sheep was due to the induced hyperkalaemia or to some other factor associated with the infusion procedure. This paper reports an investigation into the effects of potassium chloride infusion on parotid salivary flow and composition in the sheep. The possibility that the effects of potassium were mediated through the actions of hormones from either the cortex or the medulla of the adrenal gland was also investigated. * Correspondence: The Agricultural Research Council Institute of Animal Physiology. Babraham, Cambridge. 161 VOL. LX, NO CAMBRIDGE

2 162 Beal, Budtz-Olsen and Clark METHODS Experimental procedures The experiments were performed on 5 intact and 5 adrenalectomized Merino ewes weighing kg and 3 intact Clun Forest ewes weighing kg. The sheep were conscious throughout the experiments and were neither pregnant nor lactating. All animals had unilateral re-entrant cannulations of the parotid salivary duct using the technique of Stewart and Stewart [1961], but modified by reducing the diameter of the re-entrant loop so that the entire cannula except for the joining ferrule was lodged under the skin below the eye. The adrenalectomies were completed at least 1 month before the experiments and the sheep were maintained on 5 mg deoxycorticosterone acetate and 15 mg cortisone acetate given once daily at approximately hr. The sheep were fed lucerne chaff (1000 g/day) and had free access to water and to a mineral salt lick. The relative proportions of sodium, potassium, bicarbonate, phosphate and chloride in the salt lick were similar to those of parotid saliva from sodium-replete sheep. Any uneaten food was removed hr before the infusions, while access to water continued until the experiment began. Onthe morning ofthe experiment before any other procedure a small sample of saliva was collected to allow accurate assessment ofits sodium/potassium ratio: all intact sheep had salivary sodium/potassium ratios greater than 30:1 at the commencement of infusion. A short vinyl extension tube was connected to the parotid cannula at the joining ferrule to allow collection of saliva in polypropylene tubes held on a neck collar. The tubes of 15 ml. capacity were closed except for a small stainless steel air-bleed. Before each infusion experiment, a Malecot catheter (14-16 F.G.) was inserted into the urinary bladder and both jugular veins were cannulated. The animals were restrained on leather stretchers in a normal upright position with their feet just off the floor. Before commencing the infusions, saliva was collected for 15 min (control period) with a blood sample being taken mid-period. A solution of M-NaCl was infused for 2 hr into one jugular vein followed by a 2 hr infusion of either 0-43 M-KC1 or 0-43 M-NaCl and then returning to the M-NaCl for the next 2 or 3 hr. All infusions were given at 2 ml./min and all infusates contained 1-5 g inulin and 0*60 g sodium para-aminohippurate/100 ml. Throughout the infusions, saliva was collected over 15 min intervals with blood samples being taken at the middle of each salivary collection. Blood was collected directly into heparinized glass centrifuge tubes and centrifuged at 3500 r.p.m. to provide plasma for analysis. To reduce the degree of psychic distress suffered by the sheep, which is known to influence salivary flow and composition [Denton, 1957a], pairs of sheep were infused simultaneously in the same room which had a background of continuous sound provided by a radio to mask sounds from outside. The infusion of sodium chloride solution before the potassium infusion ensured that endogenous mineralocorticoid levels would be low at the commencement of the experiments. Analytical procedures The estimations of concentration of ions in the saliva and plasma of the sheep were done as follows: 1. Sodium and potassium by flame photometry using mixed standards. 2. Chloride either with a Buchler-Cotlove chloridometer or by the potentiometric method of Sanderson [1952]. 3. Salivary bicarbonate by the titration procedure of Gyory and Edwards [1967] modified for 1 ml. aliquots. Salivary ph was taken immediately after the 15 min collection period and any loss of CO2 during the period of collection leads to underestimation of the salivary bicarbonate concentration. 4. Total inorganic phosphate by the method of Baginski, Foa and Zak [1967].

3 KCI Infusion and Parotid Saliva Secretion 5. Salivary ph was measured with a Radiometer micro-electrode at 380 immediately following collection. 163 Statistical procedures The single classification analysis of variance of residuals technique as described elsewhere [Beal et al., 1973] was used to compare the 3 treatments during the 2 hr period when 0-43 M-NaCl was infused into intact sheep and 0-43 M-KCI was infused into intact or adrenalectomized sheep. A separate analysis was performed for each of the 11 variables shown on the ordinate of Fig. 1 and for each of the 8 collection periods during the hyperosmotic test infusions (total of 88 analyses). The 2 covariates used in the analyses of any variable were the control value of that variable (shown as closed circles on the figure) and the value for the last sample collected just prior to the commencement of the hyperosmotic infusions. The results were then further analysed using Tukey's w-procedure (i.e. honestly significant difference (hsd) procedure) as described by Steel and Torrie [1960]. The results of the hsd analyses are presented as levels of significance in Table I. RESULTS Hyperosmotic sodium chloride infusion into intact sheep (5 replications) The infusion of hyperosmotic sodium chloride resulted in increases in the plasma concentrations of sodium and chloride with little change in the concentrations of potassium and phosphate (Fig. 1). Changes in salivary flow rate appeared to be unrelated to the changes in plasma concentration of the infused ions. However, the concentration of bicarbonate in the saliva was directly correlated with the salivary flow rate (r = +0 77; P < 0-001) whereas salivary phosphate was inversely correlated with flow (r = -0-60; P < 0-01). The concentration of sodium in the plasma was correlated with the salivary sodium concentration (r = +0-89; P < 0-001) but the chloride concentrations of saliva and plasma showed a poor correlation (r = +0-23). Hyperosmotic potassium chloride infusions The infusion of hyperosmotic potassium chloride into both intact and adrenalectomized sheep increased the plasma potassium and chloride concentrations without altering the sodium and phosphate concentrations (Fig. 1). Statistically there were no differences in the plasma potassium concentrations between the treatments in which potassium was infused and none in the plasma chloride concentrations between any of the treatments. Intact sheep (5 replications). In the intact sheep, the salivary flow rate fell with increasing plasma potassium concentration to reach levels significantly lower than during the corresponding time intervals of the hyperosmotic sodium chloride infusion (Fig. 1; Table I). Salivary flow rate rose again as the plasma potassium levels fell at the end of the potassium infusion so that a significant inverse relationship was found through the entire period of saliva collection (r = -0-92; P < 0-001). The relationship between salivary and plasma potassium concentrations during the infusion of potassium had two obvious phases. During the initial phase which lasted at least 75 min, the salivary potassium concentration increased slightly more rapidly than the plasma concentration. After this early period, salivary potassium concentration increased

4 164 Beal, Budtz-Olsen and Clark more rapidly until the potassium infusion ended and did not fall for a further 90 min although the plasma potassium concentration had been declining (Fig. 1). Salivary sodium showed reciprocal changes in concentration of PILASMA K concn. m-mole/l. 3L-I Na concn. 160 r-mole/i Cl concn. 120 m-mole/l Loo0L - 2r P04 concn. m.mole/i 0 l- No REPLETION ~-NaCl-4 No REPLETION ADRENALECTOMIZED r- r- -K- _. 4- Kn t _j -0~ -* I ] ] SALIVA 1 Flow rate mi./min rnmoe/ 400 K concn. m-mole/l. O Na concn. m-mole/l. HCO3 concn. mrn-mole/l. 120 _ _ 30 P04 concn. m-mole/l.. Cl concn. 35 m-mole/l. 20 ph 7.[ ~~,r~~hrrl *11 ij -L,J.Ll P-L I I.. I IL-,, "If, 4~ * 0 - I I. I I TIME FIG. 1. Mean values for the plasma potassium, sodium, chloride and phosphate concentrations; salivary flow rate; salivary potassium, sodium, bicarbonate, chloride and phosphate concentrations; and salivary ph during the intravenous infusion of hyperosmotic NaCl and KC1 into sodium-replete intact sheep and adrenalectomized sheep. periodicity similar to potassium except that salivary sodium concentration did not fall appreciably during the initial 75 min of potassium infusion. The second phase of rapid change in salivary sodium and potassium concentrations did not occur in one replication of this treatment, explaining the decline in the statistical significance of differences in potassium concentration during the (hours) 0 -i 1

5 KCl Infusion and Parotid Saliva Secretion 165 last 2 periods of potassium infusion (Table I). The concentration of bicarbonate in the saliva of this group fell during the potassium infusion to levels significantly lower than those of the hyperosmotic sodium chloride treatment (Fig. 1; Table I) and was directly correlated with salivary flow rate throughout the entire period of salivary collection (r = +0 93; P < 0 001). In contrast, salivary chloride concentration rose to be significantly higher than that during the hyperosmotic sodium chloride infusion (Fig. 1; Table I) and was negatively correlated with salivary flow for the entire experiment (r = -093; P < 0-001). Salivary phosphate concentrations also varied in the opposite direction to the changes in flow rate (r = -0-86; P < 0 001). TABLE I. Summary of the final hsd analyses of parotid salivary flow rate and of the electrolyte concentrations in plasma and saliva for the eight 15 min salivary collection periods during the intravenous infusions of 0 43 M-NaCl into intact sheep and of 043 M-KCI into intact sheep and into adrenalectomized sheep. Every variable on the ordinate of Fig. 1 was tested and omission of a comparison from this table means that no significant differences were found. Differences are indicated as levels of significance (* = P <005; ** = P < 001; ** = P < 0001; = not stgnificant). Variable Comparisons Collection period of the test infusion degrees of KCl- KCl- KClfreedom= 12 infused infused infused Intact Adrenal-X Intact versus versus versus Plasma K concn. NaCl ** * *** *** *** *** *** *** NaCl ** *** *** *** *** *** *** *** Plasma Na conon. NaCl * * * NaCl - * ** * ** Saliva flow NaCl ** ** *** *** *** NaCl - * * ********* Saliva K concn. NaCl - ** *** *** *** ** * * NaCl - *** *** *** *** ** Saliva Na conen. NaCl * * * Adrenal-X * * Saliva HCO3 concn. NaCl * * NaCl - * Saliva Cl conon. NaCl * * $* ** *** ** * NaCl ** ** *** *** *** *** *** Adrenal-X -** - * Adrenalectomized sheep (5 replications) The infusion of hyperosmotic potassium chloride into adrenalectomized sheep led to a fall in the flow of parotid saliva similar to that seen in the sodiumreplete intact animals receiving the same treatment (Fig. 1; Table I). Salivary flow rate was negatively correlated with the plasma potassium concentration throughout the experiments (r _ -095; P < 0 001). The saliva was slightly higher in potassium concentration than the plasma throughout the experiments (r = +095; P < 0 001) and changes in plasma sodium tended to be reflected in the salivary sodium concentration (r = +069; P < 0 001). As the salivary flow fell during the potassium infusion, the salivary bicarbonate concentration decreased and the chloride concentration increased to levels significantly

6 166 Beal, Budtz-Olsen and Clark different from those of the hyperosmotic sodium chloride infusion (Fig. 1; Table I). Both salivary bicarbonate and chloride concentrations could be related to salivary flow (r = +095; P < and r = -0-96; P < respectively). DIscussIoN The denial of food for a period before each infusion ensured that the sheep were unlikely to masticate or ruminate during the experiment thus allowing the salivary flow rate to stabilize at the resting value for an innervated gland. During potassium chloride infusion there was a progressive decline in parotid salivary flow associated with the increasing plasma potassium concentration, which was also negatively correlated with the plasma chloride concentration and with plasma osmolality during this treatment. Increases in plasma chloride concentration and osmolality similar in magnitude to those produced by the potassium chloride treatment were produced during the equimolar infusions of hypertonic sodium chloride but without a concurrent fall in salivary flow. Therefore, the fall in flow during potassium chloride infusion was due to the induction of hyperkalaemia and, since the negative correlation between plasma potassium and salivary flow was maintained during the recovery period following the potassium infusion, the resting rate of salivary secretion appears to depend on the concentration of potassium in the plasma at any one time. Yet potassium infusions into cats and dogs have been found to either have no effect on flow or to increase flow [Feldberg and Guimarais, 1936; Langley et al., 1958; Burgen, 1961]. Salivary flow rate in the sheep has been shown to vary with the rate of blood flow through the parotid gland [Coats, Denton, Goding and Wright, 1956; Denton, 1957b]. As potassium is a vaso-active ion, the fall in salivary flow during acute hyperkalaemia may simply reflect a general fall in systemic blood pressure and cardiac output. The rate of plasma flow through the kidney, an organ whose function is also highly dependent on the maintenance of blood pressure and flow, has been reported to increase during potassium infusion [Beal et at., 1973; 1974]. In addition, measurements of carotid artery blood pressure and of total blood flow through the head of conscious sheep receiving potassium infusions have shown that the plasma potassium concentration must exceed 6x5 m-mole/l. at least before either blood pressure or blood flow were depressed below pre-infusion levels by hyperkalaemia [Beal, unpublished observations]. These data do not rule out a regional alteration in haemodynamics within the parotid gland itself. In a number of experimental situations, the hormones of the adrenal gland have been implicated in the alteration of salivary composition and flow rate but the evidence with respect to flow is conflicting. In the sheep, low salivary flow rates have been observed during sodium depletion when the salivary Na/K ratio has been lowered by the action of high levels of circulating mineralocorticoid. Although hyperkalaemia acts directly on the adrenal gland to release aldosterone and frequently corticosterone [Funder, Blair-West, Coghlan,

7 KCI Infusion and Parotid Saliva Secretion Denton, Scoggins and Wright, 1969] the administration of aldosterone into sheep and dogs had no acute effect on salivary flow [Blair-West, Coghlan, Denton, Goding and Wright, 1963; Langley, Beall and Smith, 1959]. The injection of ACTH increases parotid salivary flow in intact dogs but not in adrenalectomized dogs [Langley et al., 1959]. However, increased release of ACTH by potassium has been produced by extracellular concentrations far in excess of physiological levels [Kraicer, Milligan, Gosbee, Conrad and Branson, 1969] and infusions of cortisol and corticosterone did not depress parotid salivary flow in the sheep [Blair-West et al., 1963]. Elevation of the plasma potassium concentration increased the release of adrenaline from the adrenal medulla [Feldberg and Guimarais, 1936; Katz and Katz, 1937; Vogt, 1952]. The injection of adrenaline into the carotid artery may reduce parotid salivary flow in the sheep but injection into the abdominal aorta increases salivary flow particularly when the secretomotor nerve is intact [Kay, 1958]. The depression of salivary flow in the adrenalectomized sheep by potassium infusion (Fig. 1) eliminates any possibility that the adrenal gland was necessary for this response. The parotid gland of the sheep exhibits a period of latency in response to the administration of aldosterone which lasts min [Blair-West et al., 1963]. The fall in mean salivary Na/K ratio commencing after 75 min of potassium infusion can be interpreted as being due to increased aldosterone secretion as elevated potassium concentrations in the plasma perfusing the adrenal gland are known to increase aldosterone release. Up to this point in the potassium infusion into intact sheep, and for the entire duration of the experiments on adrenalectomized sheep, the salivary potassium concentration was linearly related to the plasma potassium level. A similar dependence of the salivary potassium concentration on plasma levels has been reported for both the parotid and submaxillary salivas in the dog [Burgen, 1956]. Although the sodium concentration of saliva has been found to vary with the rate of flow from parotid and submaxillary glands of dog, cat and man [Brusilow and Cooke, 1959; Gregersen and Ingalls, 1931; Langstroth, McRae and Stavraky, 1938; Thaysen, Thorn and Schwartz, 1954; Hildes, 1955] this relationship was not apparent in the results of the present experiments in sheep. However, the salivary sodium concentration was positively correlated with the plasma sodium concentration during both the hyperosmotic sodium chloride treatment and the potassium chloride infusion into adrenalectomized sheep (Fig. 1) where the salivary sodium level would not be influenced by fluctuating mineralocorticoid levels. A similar relationship has been reported for parotid saliva of the dog [Langley et al., 1958]. As in other species, the concentration of bicarbonate in the parotid saliva of sheep is positively dependent on the flow rate, whereas the phosphate concentration is negatively related to flow [McDougall, 1948; Denton, 1956; Coats and Wright, 1957; Kay, 1960]. In all experiments in this study the relationships between flow and the concentrations of bicarbonate and phosphate in the saliva were as found by the previous authors. The chloride concentration in parotid saliva of dog and man increases with increasing flow [Thaysen et al., 167

8 168 Beal, Budtz-Olsen and Clark 1954; Hildes, 1955; Brusilow and Cooke, 1959] whereas, in the sheep, increased parotid salivary flow was associated either with variable chloride concentrations and a tendency for higher flow rates to have lower concentrations [Coats and Wright, 1957] or with increased chloride levels [Kay, 1960]. During the potassium chloride infusions the chloride concentrations of the saliva always rose as the salivary flow fell. The reason for the variability in chloride results between authors may depend upon the method by which the salivary flow rate was altered. These data raise the possibility that changes in either the potassium concentration or the sodium/potassium ratio of the plasma may regulate the basic rate of parotid salivary secretion. From the available evidence it would seem likely that the mechanism by which hyperkalaemia depresses parotid salivary flow must contain a neural component. ACKNOWLEDGMENTS We are indebted to Mrs M. Ford and Mr P. Burrow for skilful technical assistance, to Mr I. Horton for advice on statistics and to Dr K. G. Johnson and Dr M. W. Stanier for constructive criticism of this manuscript. This work was supported by grants from the Australian Wool Board and the Rural Credits Development Fund of the Reserve Bank of Australia. REFERENCES BAGINSKI, E. S., FOA, P. P. and ZAx, B. (1967). Microdetermination of inorganic phosphate, phospholipids and total phosphate in biologic materials. Clinical Chemistry, 13, BEAL, A. M., BUDTZ-OLSEN, 0. E., CLARK, R. C., CROSS, R. B. and FRENCH, T. J. (1973). / Renal and salivary responses to infusion of potassium chloride, bicarbonate and phosphate in Merino sheep. Quarterly Journal of Experimental Physiology, 58, BEAL, A. M., BUDTZ-OLSEN, 0. E., CLARK, R. C., CRoss, R. B. and FRENCH, T. J. (1974). Renal function and salivary potassium secretion during potassium chloride infusion into sodium-deficient sheep. Quarterly Journal of Experimental Physiology, 59, BLAIR-WEST, J. R., COGHLAN, J. P., DENTON, D. A., GODING, J. R. and WRIGHT, R. D. (1963). The effect of aldosterone, cortisol and corticosterone upon the sodium and potassium content of sheep parotid saliva. Journal of Clinical Investigation, 42, BRusILOW, S. W. and CooxE, R. E. (1959). Role of parotid ducts in secretion of hypotonic saliva. American Journal of Physiology, 196, BURGEN, A. S. V. (1956). The secretion of potassium in saliva. Journal of Physiology, 132, BURGEN, A. S. V. (1961). In Burgen, A. S. V. and Emmelin, N. G., Physiology of the Salivary Glands, pp Edward Arnold, London. COATS, D. A., DENTON, D. A., GODING, J. R. and WRIGHT, R. D. (1956). Secretion by the parotid gland of the sheep. Journal of Physiology, 131, COATS, D. A. and WRIGHT, R. D. (1957). Secretion by the parotid gland of the sheep: The relationship between salivary flow and composition. Journal of Physiology, 135, DENTON, D. A.- (1956). The effect of Na+ depletion on the Na+: K+ ratio of the parotid saliva of the sheep. Journal of Physiology, 131, DENTON, D. A. (1957a). A gregarious factor in the natural conditioned salivary reflexes of sheep. Nature, 179, DENTON, D. A. (1957b). The study of sheep with permanent unilateral parotid fistulae. Quarterly Journal of Experimental Physiology, 42,

9 KCI Infusion and Parotid Saliva Secretion 169 FELDBERG, W. and GUIMARAIS, J. A. (1936). The liberation of acetylcholine by potassium. Journal of Physiology, 86, FUNDER, J. W., BLAIR-WEST, J. R., COGHLAN, J. P., DENTON, D. A., SCOGGINS, B. A. and WRIGHT, R. D. (1969). Effect of plasma [K+] on the secretion of aldosterone. Endocrinology, 85, GREGERSEN, M. I. and INGALLS, E. N. (1931). The influence of rate of secretion on the concentrations of potassium and sodium in dog's submaxillary saliva. American Journal of Physiology, 98, GYORY, A. Z. and EDWARDS, K. D. G. (1967). Simultaneous titrimetric determination of bicarbonate and titratable acid in urine. Australian Journal of Experimental Biology and Medical Science, 45, HILDES, J. A. (1955). Glandular secretion of electrolytes. Canadian Journal of Biochemistry and Physiology, 33, KATZ, G. and KATZ, G. (1937). The action of potassium chloride and of calcium chloride on the adrenals of the cat. Journal of Pharmacology and Experimental Therapeutics, 59, KAY, R. N. B. (1958). The effects of stimulation of the sympathetic nerve and of adrenaline on the flow of parotid saliva in sheep. Journal of Physiology, 144, KAY, R. N. B. (1960). The rate of flow and composition of various salivary secretions in sheep and calves. Journal of Physiology, 150, KRAICER, J., MILLIGAN, J. V., GOSBEE, J. L., CONRAD, R. G. and BRANSON, C. M. (1969). In vitro release of ACTH; effects of potassium, calcium and corticosterone. Endocrinology, 85, LANGLEY, L. L., BEALL, W. A. and SMITH, J. A. (1959). Acute effect of ACTH, aldosterone, sodium and potassium on parotid secretion. American Journal of Physiology, 197, LANGLEY, L. L., GUNTHORPE, C. H. and BEALL, W. A. (1958). Parotid clearance of sodium and potassium. American Journal of Physiology, 195, LANGSTROTH, G. O., McRAE, D. R. and STAvRAKY, G. W. (1938). The secretion of protein material in parasympathetic submaxillary saliva. Proceedings of the Royal Society (Series B), 125, MCDOUGALL, E. I. (1948). Studies in ruminant saliva. I. The composition and output of sheep's saliva. Biochemical Journal, 43, SANDERSON, P. H. (1952). Potentiometric determination of chloride in biological fluids. Biochemical Journal, 52, STEEL, R. G. D. and TORRIE, J. H. (1960). Principles and Procedures in Statistics, pp McGraw-Hill, New York. STEWART, W. E. and STEWART, D. G. (1961). Technique for cannulation of the parotid salivary duct of sheep. Journal of Applied Physiology, 16, THAYSEN, J. H., THORN, N. A. and SCHWARTZ, I. L. (1954). Excretion of sodium, potassium, chloride and carbon dioxide in human parotid saliva. American Journal of Physiology, 178, VOGT, M. (1952). The secretion of the denervated adrenal medulla of the cat. British Journal of Pharmacology and Chemotherapy, 7,