Clinical Science (1985)68,441-447
44 1
Is salt reabsorption in the human sweat duct subject to
control?
V. S C H W A R Z
AND
I . M. N A O M I SIMPSON
Departments of Chemical Pathology and Child Health, University of Manchester, Manchester, U.K.
(Received 2 July/12 October 1984; accepted 29 October 1984)
Summary
1. There is a time lag between the beginning
of sweat secretion and fully effective production
of fluid of minimum salt content. It is suggested
that changes in permeability t o water or electrolytes have to be effected and may account for the
time lag.
2. The composition of thermal and pilocarpine
sweat indicates that pharmacological stimulation
does not wholely reproduce the physiological
mechanism : pilocarpine sweat contains more
sodium and more cyclic AMP, irrespective of the
secretory rate.
3. The sweat obtained from patients with
cystic fibrosis has been compared with that
from normal children: the concentrations of cyclic
AMP and cyclic GMP are the same. Defective
sodium reabsorption in the patients is therefore
unlikely to be due to inadequate or excessive
synthesis of these cyclic nucleotides.
Key words: cystic fibrosis, sweat, sweat glands.
Introduction
Little is known of the mechanisms which control
the sodium concentration of sweat. In view of the
greatly raised salt content of the sweat of children
with cystic fibrosis (CF), a greater understanding
of the factors bearing on the salt excretion is of
obvious importance.
Even in the healthy population the salt content
of the sweat varies widely and it increases with
age. Thus an infant’s sweat may contain as little
as 10 mmol of Na/l and a normal adult’s as much
Correspondence: Dr V. Schwarz, Department
of Biochemistry, University of Manchester, Oxford
Road, Manchester M13 9PT, U.K.
as 100 mmol/l; CF children’s sweat covers the
range 70-140 mmol/l. The age-related variations
may well depend on salt intake and hence aldosterone output. It also depends, as in other glands,
on the rate of secretion.
The structure of the gland is perfectly suited to
its function. The secretory coil is essentially a
blind sac into which open intercellular canaliculi,
lined by two types of cells believed to be concerned with the transport of salt and fluid into the
lumen and with the production of mucus, and
myoepithelial cells lying on the basement membrane. Coiling intimately around the secretory
portion is the proximal duct which is lined by only
a single type of cell whose task it is to reabsorb
much or most of the salt from the isotonic
precursor fluid, so leaving a grossly hypotonic
sweat to reach the surface of the skin via the
distal straight duct (for a recent review see [l]).
The advantage of the closely coiled secretory
portion and the reabsorptive duct is apparent: Na’
or C1- is transferred actively from the interstitium
into the lumen, followed b y water, and the salt is
reabsorbed from the duct lumen into the interstitium, ready to be recycled for what is essentially
water transport.
Sutcliffe et ul. [2] have proposed that the
reabsorptive function of the sweat gland, like the
secretion of primary fluid, may be subject to
control, t o be switched on when the gland becomes active, and that the poor reabsorption of
salt in CF may be due t o a failure to operate the
switch.
The suggestion arose from the finding, later
confirmed and greatly amplified in several hundred
routine sweat tests for the diagnosis of CF (V.
Schwarz & I. M. N. Simpson, unpublished work),
that the sodium concentration of the sweat
frequently declined over the course of a sweat
442
V. Schwarz and I. M. N. Simpson
collection after a single cholinergic stimulation,
despite a steady or even increasing secretory rate.
This behaviour is contrary to what would be
expected of a gland with a fured reabsorptive
potential which becomes progressively more
limiting as the secretory rate rises [3]. The falling
sodium concentration of surface sweat in these
circumstances was interpreted to signify a
gradually increasing reabsorption of salt in the
duct, triggered either directly by acetylcholine or
by intermediaries like cyclic AMP, cyclic GMP,
prostaglandin or bradykinin, whose potential
participation in sweat gland function has since
been demonstrated by Khullar et al. [4]. It is
known that bradykinin is formed upon stimulation
of the gland [5] and is believed to dilate blood
vessels to the gland and so ensure an adequate
supply of glucose and water, but it may have other
functions.
The present studies represent an attempt t o
answer two questions:
(1) Is reabsorption of NaCl in the sweat duct
subject t o short-term control?
(2) If so, is it separate from and additional to
the stimulation of secretion?
We employed four strategies in approaching these
questions: (i) measurement of the sodium concentration and secretory rate of sweat from single
glands over a time course immediately after
stimulation t o detect any possible delay in switching on reabsorption; (ii) comparison of sweat
(from many glands) obtained after pharmacological or thermal stimulation with respect to
secretory rate, sodium concentration and cyclic
AMP; (iii) comparison of normal and CF subjects
with respect to cyclic AMP and cyclic GMP in
the sweat; (iv) assessment of any effect on sweat
sodium of local administration of a variety of
humoral agents or their antagonists.
Materials and methods
Collection of sweat from single glands
The volar surface of the subject's lower forearm
was washed and dried. A perspex frame with
silicone rubber base was strapped to the site such
that it could hold liquid paraffin without leaking.
Pilocarpine was ap.plied to the centre of the frame
area via an anode made of filter paper rolled to a
point and fitted into a capillary tube filled with
pilocarpine nitrate solution. A current of 65 pA
was passed for 45-6Os, a wet band round the
upper arm serving as the cathode. After the
stimulated area had been quickly wiped, the
frame was filled with paraffin at 34"C, previously
saturated with water at the same temperature.
With the use of a stereomicroscope sweat was
collected from a single gland into a fine polythene
capillary filled with paraffin and attached to a
small chamber fitted with a screw to act as a
microsyringe. Each droplet, after reaching an
appropriate size, was sucked into the capillary,
followed by a little paraffin until, after 3-5 min,
five or six droplets had been collected. The length
of each droplet was measured under the microscope in a silica capillary of known diameter. The
sweat was then transferred to a short polythene
tube where it was allowed to evaporate to dryness.
After dissolving and diluting the residue with
water, aliquots were transferred to the graphite
rod of an atomic absorption spectrophotometer
(Shandon Southern) for determination of Na. At
least five aliquots of the samples and of each
standard were used and median values were taken
as the sodium content of the aliquot. The
precision of the whole procedure was assessed
by using droplets of standard NaCl solution
(40-160 mmol/l) deposited under paraffin on a
polythene sheet. The coefficient of variation
(100 S D / ~ )in eight determinations was 3.6.
Standard collection of mixed sweat from many
glands
We used our routine method for the diagnostic
sweat test previously described [2]. Briefly, it
consists of passing a current of 1.3 mA for 6 min
via a graphite anode (2 cm x 1.5 cm) and a stack of
filter paper soaked in pilocarpine nitrate into an
area of skin on the volar surface of the forearm.
After wiping and drying the stimulated site, it is
covered with a square of washed X-ray film of
the same dimensions, sealed to the skin by flexible
polythene adhesive tape (Lasso, Smith and
Nephew) on three sides. Weighed filter paper
squares are inserted via the open end, which is
sealed with tape. The papers are changed every 5
min, weighed and eluted chromatographically. The
sodium and potassium concentrations are determined by flame photometry.
Administration of drugs
This was mostly by iontophoresis into the site
from which sweat was to be collected. Some
drugs were injected intradermally in a volume
of 50pl of 0.9% (w/v) NaCl solution, usually
before pilocarpine iontophoresis. Alternatively,
both drug and pilocarpine were injected together.
In each case the dose was based on the known
activity of the drug and on the estimated concentration likely to be achieved in the vicinity of the
sweat glands.
Salt reabsorption in the sweat gland
Determination of cyclic nucleotides in sweat
Sweat was collected on 3 cm x 3 cm papers
from an area of the same dimension stimulated
with pilocarpine at 4 mA for 6 min. Heat stimulation was carried out by immersing one arm in a
water bath at 45°C and collecting sweat on four
3 cm x 3 cm papers on the other arm.
The papers were eluted with water, the eluates
were evaporated to dryness in vacuo in two
replicates and the residues were dissolved in
buffer for determination of cyclic nucleotides with
the kits supplied by Amersham International.
Drugs
All biochemicals were obtained from Sigma.
Piroxicam was supplied by Pfizer Ltd (Sandwich,
Kent, U.K.).
Results
Single gland study
Collection and analysis of individual sweat
droplets enables the changes in sodium concentra-
443
tion to be studied over a short time course (3-5
min) and free from interference by slower or faster
secreting glands. Since a falling secretory rate
would be expected to result in a declining sodium
concentration, it is useful t o consider only those
tests in which the secretion rate remained
reasonably steady or rose during the collection.
This condition was realized in ten experiments on
six subjects. The sodium concentration fell substantially in the course of the first few minutes. It
can be seen from Table 1 that in two experiments
(1 and 10) the main fall in sodium concentration
was recorded in sample 2, whereas in the others
it was distributed over several or all samples,
especially when due allowance is made for a rise
in secretory rate (experiments 5 , 7 and 9).
Comparison of thermal and pilocarpine sweat
A glance at Table 2 will show that our standard
pharmacological stimulation induced a higher
secretory rate than the thermal stimulation we
selected initially, no doubt reflecting t o some
extent the relative strengths of the two stirnuli.
The greater rate is associated with a higher sodium
TABLE 1. Sodium concentration and secretory rate of serial samples of pilocarpine
sweat from single glands, collected over 3-4 min after stimulation
Expt.
no.
Sample
no.
[Na]
(mmol/l)
Secretory rate
(nl/min)
Expt.
no.
Sample
no.
1
1
2
3
4
5
63
34
26
37
31
1.5
1.5
1.3
1.5
1.5
6
1
2
3
4
5
6
91
75
65
67
54
0.87
1.4
1.2
1.3
1.1
2
1
2
3
4
5
108
94
88
73
74
0.72
0.76
0.72
0.66
0.66
7
1
2
3
4
106
85
79
78
2.4
2.6
3.5
3.2
3
1
2
3
4
63
50
35
37
4.0
7.6
8.4
1.2
137
135
115
112
107
0.48
0.56
0.66
0.65
0.59
4
1
2
3
4
5
103
79
79
76
69
4.8
5.8
5.2
6.1
6.1
9
1
2
3
4
5
151
163
137
124
120
0.61
0.69
0.83
0.97
1.1
5
1
2
3
4
5
94
89
86
84
83
2.3
2.8
3.1
7.3
8.3
10
1
2
3
4
5
68
54
56
65
58
2.3
2.2
2.3
1.9
2.0
8
[Na]
Secretory
(mmol/l) rate (nl/min)
TABLE2. Comparison of secretory rate, electrolytes and cyclic AMP in thermal and pilocarpine sweat of normal adults
X
ix
ix
Viii
Vi
Viii
vi
V
V
V
V
iii
iv
U
i
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
no.
Subject
Expt.
no.
3.5
4.9
5.8
7.1
7.6
23.0
10.7
11.7
7.0
5.6
8.6
25.7
7.7
18.3
6.3
(mg 5 min-l 3 cm-’)
Secretory rate
~~
~
18.3
30.3
23.4
19.6
55.0
77.8
66.6
66.5
21.6
18.1
39.1
74.0
10.1
17.0
17.6
“a1
(mmol/l)
[KI
8.8
10.9
7.7
6.6
7.7
6.0
5.1
5.4
10.9
9.8
6.5
5.2
6.9
8.2
6.3
(mmol/l)
Thermal
[Cyclic AMP]
Secretory rate
0.5 1
0.21
0.11
0.16
0.30
0.11
0.23
-
-
-
0.21
0.53
0.09
0.1 1
-
-
41.9
-
43.9
60.2
48.0
55.3
34.0
105.3
101.8
83.8
85.0
41.3
42.7
77.3
“a1
(mmol/l)
18.8
20.7
-
22.0
8.4
11.1
14.9
7.4
5.1
12.5
9.8
20.2
13.9
18.2
(pmo1/100 mg of sweat) (mg 5 min-’ 3 cm-’)
5.6
-
-
-
8.4
-
0.42
0.81
-
-
-
-
0.88
0.44
0.52
1.72
0.86
0.66
0.83
[Cyclic AMP]
(pmo1/100 mg of sweat)
6.6
11.0
8.1
7.6
10.9
11.4
7.9
7.3
6.5
8.3
7.2
[KI
(mmol/l)
Pilocarpine
In experiments 6 , 12 and 14 the subjects were heated more strongly in order to produce higher secretory rates and pilocarpine was reduced to 25% of the
normal dose in experiment 6 t o lower the rate. Electrolytes and rates are the means of individual values obtained from four consecutive 5 min collections;
cyclic AMP was determined, in duplicate, in the pooled sweat.
21
9
F
2
&
.+
3
Q
E1
;3
z
2
s.
.c,
P
P
P
Salt reabsorption in the sweat gland
the .cyclic AMP was substantially lower in thermal
sweat.
Although thermal sweat contains less cyclic
AMP and less sodium, establishment of a causal
relationship between the two variables in the same
subject is not possible on the basis of the present
data. Between subjects, plots of cyclic AMP vs
sodium concentration, both in thermal sweat
secreted at rates varying from 5 to 8.6 mg/5 min
and in pilocarpine sweat secreted at rates of 14 to
22 mg/5 min, show no correlation.
concentration in every case, whereas the potassium
is more variable. In experiments 6, 12 and 14 the
subjects were therefore heated more strongly in
order to induce higher secretory rates; in addition,
pilocarpine stimulation was reduced to 25% of
the normal dose in experiment 6.
Although the thermal secretory' rate achieved
in experiment 12 is 40% higher than that induced
by standard pilocarpine in experiment 11, the
sodium is a little lower. Comparison of thermal
sweat in experiment 14 with pilocarpine sweat
in experiment 13 shows the considerable disparity
in sodium concentration despite an almost equal
secretory rate. The same is true of experiments 5,
7 and 8. In experiment 6 the sodium concentration of thermal sweat is substantially lower than
that of pilocarpine sweat, despite a four times
greater secretory rate.
The amounts of sodium reabsorption from
thermal and pilocarpine sweat by the duct can be
compared on the assumption (a) that the primary
fluid secreted by the sweat coil is iso-osmotic
with plasma and contains 140 mmol of sodium/l
(the plasma sodium was not determined) and
(b) that the reabsorption of water is the same in
both types of sweat. In experiments 5, 7 and 8
thermal and pilocarpine sweat were collected
within 90 min of each other and the sweating rates
obtained by the two kinds of stimulation were
similar. On this basis the amounts of sodium
reabsorbed from thermal and pilocarpine sweat
were as follows: experiment 5, 645 and 257
nmol/5 min; experiment 7, 785 and 702; experiment 8,860 and 539.
The cyclic AMP concentration was lower in
thermal sweat in all nine experiments and paired
t-tests show a difference between both cyclic
AMP concentration and output in thermal and
pilocarpine sweat which is highly significant:
Concentration: P < 0.01
P < 0.01
P < 0.01
output:
P < 0.01
Cyclic nucleotides in normal and CF sweat
When comparing pilocarpine sweat from the
two groups of children, one finds no difference
with respect to cyclic AMP and cyclic GMP,
despite the grossly deficient reabsorptive function
of the sweat duct in CF and hence the wide gap
between the respective sodium concentrations
(Table 3 and Table 4).
Effect of humoral agents and their antagonists
In over 50 experiments, cyclic A M P , cyclic
GMP, prostaglandins and inhibitors of their
respective synthetases were administered locally
before collection of pilocarpine sweat, which was
compared with control sweat collected at the same
time.
Dibutyryl cyclic AMP and putative inhibitors of
adenylate cyclase, 2'-deoxyadenosine-3'-monophosphate [6], adenosine and ATP [7], nicotinic acid
[8] and quinidine [9], had no demonstrable or
consistent effect. Dibutyryl cyclic GMP, in a
rather large dose of 0.5 mg/3 cm2 of skin, raised
the secretory rate by a mean of 16.7% and the
sodium concentration by a mean of 9%. A series
of doses of prostaglandin El and prostaglandin E2
were without effect, and the same was true of
indomethacin [ 101 and piroxicam [ 111, inhibitors
of prostaglandin synthetase.
(two-tailed)
(one-tailed)
(two-tailed)
(one-tailed)
Discussion
The single gland experiments show up clearly the
extent of the adaptation of which the glands are
Even when the secretory rates were similar (experiments 11 and 12, and experiments 13 and 14),
TABLE 3 .
445
Cyclic AMP in pilocarpine sweat from normal (N) and cystic fibrosis (CF)
children
No. of
Age range
subjects
(years)
8
4
7-14
6-14
Status
N
CF
Cyclic AMP (pmo1/100mg of sweat)
Range
Mean f SD
0.19-1.02
0.58 20.28
0.65 t0.15
0.50-0.85
V. Schwarz and I. M. N. Simpson
446
TABLE4. Cyclic GMP in pilocarpine sweat from
normal ( N ) and cystic fibrosis (CF) subject3
No. of
subjects
4
5
Status
N
CF
Cyclic GMP (pmo1/100mg of sweat)
Range
Mean
0.20-0.41
0.26-0.41
0.33
0.32
capable in the course of the first few minutes. The
substantial fall in the sodium concentration of the
sweat is not confined to the second sample, from
which we can conclude that the relatively high
sodium concentrations of earlier samples are
not due to sweat remaining in the duct after a
previous episode of sweating and concentrated by
loss of water. Since the average volume of the
sweat duct is 1.2 nl [ 121, any sweat left in the duct
would be flushed out in the first sample obtained
from the gland.
We can suggest three possible explanations for
the decreasing sodium concentration: (i) the precursor fluid elaborated in the secretory coil of
the gland is initially more hypertonic, i.e. less
water follows the pumped NaCl into the lumen
owing to relatively poor water permeability of the
secretory epithelium in the first few minutes; (ii)
less sodium chloride is reabsorbed in the coiled
duct during the early stages of secretion; (iii)
pilocarpine interferes with the reabsorption of
sodium in the duct. The last interpretation is
unlikely, since the concentration of the drug can
be assumed not to fall so rapidly in view of the
gland’s continued activity for at least 30 min and
since the sodium in the sweat obtained from many
infants in the first 2 min in our standard sweat
test can be as low as 10 mmol/l.
The alternative explanations imply the
existence of a time lag between the initiation of
secretion and achievement of the final, presumably
optimum, operating conditions. The time lag may
be due to some physiological adjustment which
the gland has to make, i.e. an increase in ion or
water permeability, perhaps in response to a
second messenger. Indeed, Mangos [ 131 has shown
that in vitro salt is reabsorbed in the sweat duct
only if it is perfused with sweat rather than with
salt solution, suggesting the presence in the natural
fluid of such a messenger or humoral agent.
Recently Quinton [14] has demonstrated in
isolated sweat glands obtained from healthy and
CF subjects that the CF duct epithelium has an
abnormally low permeability to C1-, a defect
which must greatly impair sodium chloride trans-
port and hence reabsorption. I t is not yet known
whether this low permeability is due to a
structural membrane abnormality of CF exocrine
glands or to a blockage of chloride channels by a
component of CF sweat. If the channels are
designed to open when the gland is required to
reabsorb salt, a failure to do so in CF might
account for the low permeability.
A comparison of thermal and pilocarpine
sweat shows the sodium concentration of the
former to be significantly lower than that of the
latter, irrespective of secretory rates. The same is
true of cyclic AMP. These observations point to a
failure of pilocarpine to evince, in its entirety, the
process of physiological stimulation. This conclusion would imply the existence of some
mechanism for enhancing either the permeability
to water of the secretory coil or the reabsorptive
capability of the duct. The rat parotid is well
known to show different secretion patterns in
response to direct nerve and pilocarpine stimulation [15]. Sat0 [16] also reported somewhat
higher sodium concentrations in pilocarpine sweat
of some and higher potassium in all subjects,
compared with thermal sweat. The experimental
protocol used by these investigators differed in
several respects from ours.
The performance of the sweat gland could
conceivably be modulated by differential activity
of its dual innervation, of the adenylate and
guanylate cyclase systems, prostaglandins, bradykinin and possibly other agents. Our experiments
with a- and 0-blockers (V. Schwarz & I. M. N.
Simpson, unpublished work) indicate the absence
of any adrenergic component in moderate thermal
or pilocarpine stimulation.
The gross defect of salt reabsorption in CF is
patently not due to the glands’ over- or underproduction of cyclic AMP or cyclic GMP, if
excretion in the sweat is taken as indicative of
cyclic nucleotide synthesis (Table 3 and Table 4).
However, the amount of nucleotide leaking into
the secretory fluid does not necessarily reflect the
intracellular concentration, slight changes of which
may have substantial effects 1171.
The glands’ performance could not be significantly improved or altered by exogenous cyclic
AMP in normal or CF subjects and hence we
conclude that any ‘switching on’ is probably not
mediated by that substance. Inhibition of
adenylate cyclase might have been more conclusive,
but the putative inhibitors we have used had no
demonstrable effect. Administration of cyclic
GMP did not alter the sodium concentration,
except as a consequence of an increased secretory
rate, and this remains a possible interpretation of
the pilocarpine effect.
Salt reabsorption in the sweat gland
Studies of prostaglandin actions on tissues are
notoriously difficult to interpret [ 181. In our
experiments the prostaglandins tested yielded no
definite and reproducible effects. Neither did the
structurally unrelated inhibitors of prostaglandin
synthetase, indomethacin and piroxicam, affect
the sodium concentration of the sweat.
Our experiments lead us to conclude that the
initiation of pilocarpine-induced secretion and
establishment of optimum conditions of sweat
elaboration do not occur simultaneously and that
the time gap must be due t o delayed intervention
of a substance which increases membrane
permeability to water or ions. Whether this
required permeability increase is more immediate
or complete in thermal stimulation or whether
some other factor increases the efficiency of the
process, cannot be decided but there can be no
doubt about the greater ability of the thermally
stimulated gland to conserve sodium. The
abnormal glandular function in CF may well be
referable to a failure to effect the permeability
increase.
Acknowledgments
We record our indebtedness to Mr A. K. Khullar
for carrying out some of the determinations of
cyclic AMP while in receipt of a grant from the
Cystic Fibrosis Research Trust. We are grateful
to Dr G. V. Feldman for permission to study his
patients with the consent of their parents, and to
our colleagues for subjecting themselves and their
children to the investigations.
References
1. Sato, K. (1977) The physiology, pharmacology and
biochemistry of the eccrine sweat gland. Reviews of
Physiology, Biochemistly and Pharmacology, 79, 52131.
2. Sutcliffe, C.H., Style, R.P. & Schwarz, V. (1968)
Biochemical studies of sweat secretion in cystic
fibrosis. Proceedings o f the Royal Society o f Medicine,
61,297-300.
447
3.Thaysen, J.H. (1960) Handling of alkali metals by
exocrine glands other than the kidney. In: Handbuch
der experimentellen Pharmakologie, vol. 13, pp. 424507. Springer Verlag, Berlin.
4. Khullar, A.K., Schwarz, V. & Wilson, P.D. (1985)
The human eccrine sweat gland adenylate cyclase
system: response to agonists. Clinical Science, 68,
433-439.
5. Fox, R.H. & Hilton, S.M. (1958) Bradykinin formation in human skin as a factor in heat vasodilatation.
Journal of Physiology (London), 142,219-232.
6. Sahyoun, N., Schmitges, C. J., Siegel, M.I. & Cuatrecasas, P. (1976) 2' -Deoxyadenosine-3'-monophosphate: a naturally occurring inhibitor of adenylate
cyclase in amphibian and mammalian cells. Life
Sciences, 19,1967-1970.
7. Glynn, P. & Cooper, D.M.F. (1978) Inhibition of
bovine adrenocortical adenylate cyclase activity by
adenosine. Biochimica et Biophysica Acta, 526,
605-612.
8. Turjman, N., Gotterer, G.S. & Hendrix, T.R. (1978)
Prevention and reversal of cholera enterotoxin effects
in rabbit jejunum by nicotinic acid. Journal of Clinical
Investigation, 61, 1155-1160.
9. Taylor, A. & Windhager, E.E. (1979) Possible role of
cytosolic calcium and N a C a exchange in regulation
of transepithelial sodium transport. American Journal
ofPhysiology, 236, F505-F512.
10. Vane, J.R. (1971) Inhibition of prostaglandin
synthesis as a mechanism of action of aspirin-like
drugs. Nature (New Biology), 231, 232-235.
11. Wiseman, E.H. (1978) Review of preclinical studies
with piroxicam. In: Piroxicam. International Congress
Symposium Series no. 1, pp. 11-23. Royal Society of
Medicine. London.
12. Kuno, Y. (1956) Human Perspiration. C.C. Thomas,
Springfield, Illiiois.
13.'Mangos, J.A. (1973) Transductal fluxes of Na,K and
water in the human eccrine sweat gland. American
Journal of Physiology, 224, 1235-1240.
14. Quinton, P.M. (1983) Chloride impermeability in
cystic fibrosis. Nature (London), 301,421-422.
15. Young, J.A. (1979) Salivary secretion of inorganic
electrolytes. International Review of Physiology, 19
(Gastrointestinal Physiology III), 1-58.
16. Sato, K. (1973) Sweat induction from an isolated
sweat gland. American Journal o f Physiology, 225,
1147-1152.
17. Butcher, F.R. & Putney, J.W., Jr (1980) Regulation of
parotid gland function by cyclic nucleotides and
calcium. Advances in @clic Nucleotide Research,
13,215-242.
18. Horrobin, D.F. (1978) Prostaglandins: Physiology,
Pharmacology and Clinical Significance, p. 279.
Churchill Livingstone, Edinburgh.