Iodide concentration by human labial salivary glands

Archsoral Riol. Vol. 16,pp. 1245-1249,1971.Per~amonPress.Printedin Great Britain.

SHORT COIMMUNICATION IODIDE

CONCENTRATION

BY HUMAN LABIAL SALIVARY GLANDS

D. M. CHISHOLMand K. W. STEPHEN Department of Oral Medicine and Pathology, Dental Hospital and School, University of Glasgow and J. W. K. ROBERTSON Regional Department of Clinical Physics and Bio-Engineering, Western Regional Hospital Board, Glasgow and

R. McG.

HARDEN

University Department of Medicine, Western Infirmary, Glasgow THE CONCENTRATING ability of the major salivary glands for iodide has been extensively studied (MASON,HARDENand ALEXANDER,1966a; HARDENand ALEXANDER, 1967). Iodide is concentrated by the parotid and submandibular glands to many times the plasma level and this activity is inhibited by excess iodide and by other ions, such as perchlorate. In some animals, iodide has been shown to be concentrated by the submaxillary but not the parotid gland (COHEN and MYANT, 1959). Little information is available about the chemical composition of saliva secreted by the labial salivary glands and no studies have been made of their secretion of iodide in man or in animals. The possible effect of the concentration of iodide in labial salivary glands on the interpretation of salivary gland radio-isotope scintiscans in humans has been discussed previously (HARDEN et al., 1968). The aim of this study was to investigate in man the concentration of iodide by the labial salivary glands, to study its relationship with flow rate and the effect of potassium perchlorate on the concentrating mechanism, and to compare the concentration by the labial glands with that of the parotid gland. Twenty-five normal volunteer subjects aged between 26 and 69 yr (12 female and 13 male) with no evidence of thyroid or salivary gland disease were studied. Labial saliva was collected for a period of 5-8 min commencing 20 min after the intravenous administration of 50 PCi of 1321, using a technique similar to that described by KUTSCHERet al. (1967). The subject’s lower lip was everted by an assistant, the mucosa dried with sterile gauze and a dental aspirator placed in the floor of the mouth. A few drops of citric acid (10 per cent) were applied to the dorsum of the tongue and saliva was collected in 10 ~1 capillary tubes (“Microcaps”, Drummond Scientific 1245

1246

D. M.

CHISHOLM,

K. W. STEPHEN, J. W. K. ROBERTSON AND R. McG. HARDEN

Company, U.S.A.) by capillary attraction. The collected saliva was expelled into weighed tubes which were then reweighed. Parotid saliva was collected with a modified Car&son-Crittenden cup from 16 subjects 30 min after administration of the isotope, using the same stimulant (MASON et al., 1966b). The collection was continued until approximately 3 ml saliva were obtained which took on average 2 min. In 14 volunteers, labial salivary gland tissue was obtained by a method similar to that described by CHISHOLMand MASON (1968). Six of these subjects were biopsied while under general anaesthesia to exclude the possibility of an effect from a local anaesthetic. Blood samples were obtained at 12, 25 and 35 min. The radioactivity of the saliva, plasma and gland tissue was counted in an automatic gamma scintillation-counter (Nuclear Chicago) with pulse-height analyser settings corresponding to an energy range of 520-760 keV. A standard containing an aliquot of the dose was also counted. Sample counts were corrected for background and for radioactive decay between counting of sample and standard. The activities of the plasma and saliva were expressed as percentage of dose per ml of sample and the gland activity as percentage of dose per gram. The plasma activity was plotted against time and the mean plasma activity for each saliva collection and tissue sample was calculated. With three of the subjects, immediately following the collection of parotid saliva, 500 mg potassium perchlorate crushed in water was given orally. A second labial saliva collection was commenced 15 min later, and followed as before by a parotid saliva sample. At the conclusion of this period, a further blood sample was obtained. The flow rates from the labial glands ranged from 0 -05 ~1 per min to 1.50 ~1 per min (mean O-46; SE. 0. IO). The saliva/ plasma iodide concentration ratio for labial gland saliva plotted against salivary flow rate is shown in Fig. 1. As the flow rate increased, the saliva/plasma ratio fell from a value of 74 to less than 10 at high flowrates (mean 26 -8 ; S.E. 4 - 7). The mean saliva/plasma iodide ratio in parotid saliva from the same subjects under the same conditions of stimulation was 14.9 (S.E. l-3); significantly lower than in labial saliva (P ~0.05). The degree of concentration of iodide in saliva from the labial salivary glands thus varies inversely with flow rate, as in parotid and submandibular saliva (MASON et al., 1966a). Variations in the quantity of other labial gland constituents with flow rate have been reported (WOOD and DAWE~ 1968), and, although we have found iodide to be concentrated to a greater extent in the minor gland saliva, WOOD and DAWE~ (1968) have shown this not to be true for all ions. In the stomach, iodide has been reported to be concentrated in the mucous cells (LOGOTHETOPOULOSand MYANT, 1956; HARDEN et al., 1969) and it is of interest that while the parotid is essentially a serous gland, the labial glands are purely mucous (TANDLER et al., 1969). While the differences in iodide concentration may be primarily due to the different nature of the secretions, they may be secondary to differences in flow rate by the two gland types in response to the same stimulus. Table 1 shows the results obtained when the labial gland/plasma ratio was measured in 8 volunteers. Values ranged from 0.47 to 3.08 (mean l-26; S.E. O-31). The mean value in the 6 subjects who had a general anaesthetic was not significantly different (l-56; S.E. O-36). The gland/plasma ratios were significantly lower than the salivary/ plasma ratios (mean 31.3; S.E. 7 *4), but no significant correlation was noted between

IODIDECONCENTRATION

Labial Saliva

BYHUMAN

1241

LABIAL SALNARYGLANDS

Piasma 13*1 I

soX 70-

60-

X 5o

x

40-

X

30-

x

X

X

X

20-

xxx

x X

10-

o-75

1.0

1.25

1.5

Saliva Flow Rate (+/minute)

between labial saliva/plasma ?I subjects.

FIG. 1. Relation

TABLE ~.CONCENTRATING

ratio, and salivary flow-rate in 7

POWER OF LABIAL AND PAROTID GLANDS SALIVARY FLOW

FOR

I321 ATDIFFERENTRATES

Parotid

Labial Subject

Mean S.E.M.

Flow rate &l/min)

Saliva/plasma ratio (IT)

Gland/plasma ratio (1321)

Saliva/plasma ratio (1321)

1.44

0.13 0.06 0.13 o-43 o-75 0.14 0.41

8.5 25.6 73.9 29.2 28.8 17-o 49-l 17.9

0.66 1.70 0.88 o-74 o-74 o-47 3.08 1.80

10.2 19.6 13.5 13.0 17.8 24.0 11.3

o-44 o-17

31.3 7-4

1.26 0.31

15.6 1.9

-

OF

1248

D. M.

CHISHOLM,

K. W. STEPHEN, J. W. K. ROBERTSON ANDR. McG. HARDEN

them. It is likely that, in the minor glands, as in the parotid gland where iodide is concentrated in the ductal cells, only a small proportion of cells are responsible for iodide concentration. In those cells not concerned with * j21 concentration, the tissue/ plasma ratio will be similar to that in surrounding tissues, and in animals has been shown to be approximately 0.25 (PAPADOPOULOS, MACFARLANEand HARDEN,1967). This would explain the lower overall gland/plasma iodide ratio. The lack of correlation between the labial gland/plasma ratio and saliva/plasma iodide ratio is not unexpected, as both are dependent on flow rate and the conditions of stimulation were not the same. In 7 subjects, the parotid saliva/plasma ratios were significantly lower than the labial saliva/plasma ratios (P < O-025; mean 15-6; S.E. l-9). TABLE2. EFFECT

OF PERCHLORATE FROM

ON

THE

SALIVA/PLASMA

THE LABIAL

AND

CONCENTRATION

PAROTID

RATIO

OF -‘I

IN

SALIVA

GLANDS

Labial saliva

Parotid saliva

Subject Before pxchlorate After perchlorate Flow rate *S/P Flowrate S/P 13ZI 1321 (pl/min) Wmin)

% Fall

Before perchlorate After perchlorate SIP SIP 13ZI 1321

% Fall

1 2 3

0.23 0.31 1.20

53.6 16.6 5.6

0.11 0.58 0.59

40-2 5-2 2-9

25 69 48

18.5 9.2 11.1

9.9 2.8 3.9

41 69 65

Mean

O-58

25-2

o-43

16-l

47

12-9

5.6

60

* S/P = Saliva/Plasma

ratio.

The effects of perchlorate administration on labial and parotid saliva 1321 concentration were studied in 3 subjects (Table 2). The labial saliva/plasma 1j21 ratio after perchlorate showed a mean decrease of 47 per cent of the control value, while that of the parotid saliva/plasma ratio fell by a mean value of 60 per cent. The decrease in the parotid saliva/plasma ratio was similar in one patient (69 per cent) and greater in 2 subjects. Thus perchlorate is a competitive inhibitor of iodide concentration in the labial glands as it is in the major salivary glands, although this inhibition seems to be less complete in the labial gland tissue. Acknowledgements-We should like to thank Professor D. K. MASONand Professor G. M. WILSONfor their support and Mr. I. T. JACKSON,F.R.C.S., of the Regional Plastic Surgery Unit for the West of Scotland, for his co-operation during this study. This study was supported by a grant from the Secretary of State for Scotland on the advice of the Advisory Committee for Medical Research.

CHISHOLM,

D. M. and

MASON,

REFERENCES D. K. 1968. Labial salivary gland biopsy in SjGgren’s disease. J. clin.

Path. 21, 656460. B. and MYANT, N. B. 1959. Concentration Lond. 145, 595-610.

COHEN,

of salivary iodide: A comparative study. J. Physiol.,

IODIDE CONCENTRA1?ON BY HUMANLABlAL SALIVARYGLANDS

1249

HARDEN, R. McG. and ALEXANDER, W. D. 1967. The relation between the clearance of iodide and pertechnetate in human parotid saliva and salivary flow rate. Clin. Sci. 33, 425-43 1, HARDEN, R. McG., ALEXANDER, W. D., SHIMMINS,J. and RUSSELL, R. I. 1968. Quantitative uptake measuremems of 99mTc in salivary glands and stomach and concentration of 99”Tc, Is21 and “Br in gastric juice and saliva. Radioaktive Isotope in Klinik und Forschung (edited by FELLINGER, K. and HOFER, R.) Urban and Schwarzenberg, Munich. HARDEN, R. McG., ALEXANDER, W. D., SHIMMINS, J. and CHISHOLM, D. M. 1969. A comparison between the gastric and salivary concentration of iodide, pertechnetate and bromide in man. Cur, 10,928-930. KUTSCHER, A. H., MANDEL, I. D., ZEGARELLI, E. V., DENNING, C., ERIV, A., Rurz, L., ELLEGOOD, K. and PHALEN, J. 1967. A technique for collecting the secretion of minor salivary glands : 1. Use of capillary tubes. J. Oral Therap. Pharmac. 3, 391-392. L~GOTHETOPOULOS,J. H. and MYANT, N. B. 19.56. Concentration of radioiodide and 35S-labeIled thiocyanate by the stomach of the hamster. J. Physiol. 133, 213. MASON, D. K., HARDEN, R. McG. and ALEXANDER, W. D. 1966a. The influence of flow-rate on the salivary iodide concentration in man. Archs oral Biol. 11, 235-246. MASON, D. K., HARDEN, R. McG., ROWAN, D. and ALEXANDER,W. D. 1966b. Recording the pattern of salivary flow. J. dent. Res. 45, 1458-1463. PAPADOPOULOS,S., MACFARLANE, S. and HARDEN, R. McG. 1967. A comparison between the handling of iodine and technetium by the thyroid gland of the rat. J. Endocrin. 38, 381-387. TANDLER, B., DENNING, C. R., MANDEL, I. D. and KUTSCHBR, A. H. 1969. Ultrastructure of human labial salivary glands: 1. Acinar secretory cells. J. Morphol. 127, 383-408. WOOD, C. M. and DAWES, C. 1968. The composition of lip mucous gland secretions. J. dent. Res. 47,

62.