E. A. (Edward Albert) Sharpey-Schäfer.

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carotid. Wharton's duct connected with a tube graduated in millimetres.
Gland-vein opened. The chorda tympani was stimulated for one minute, and
the rise in millimetres of the saliva in the tube was noted each five seconds.

Saliva floio.-^, 20, 70, 50, 55, 45, 36, 30, 27, 29, 30, 28 = 410.

The artery was then clamped for five minutes ; during the last minute the
chorda was stimulated, the blood flow from the vein was very slight.

Saliva floio.—Q, 0, 21, 32, 33, 17, 14, 8, 6, 7, 2, 2 = 142.'

The carotid was left undamped for eight minutes, then clamped for one
minute, during which the chorda was stimulated.

Saliva floiv.—O, 0, 0, 2, 4, 6, 5, 5, 5, 4, 5, 4 = 40.

The carotid was undamped, but the stimulus kept up for two minutes.
The blood flow from the vein was moderately increased. The saliva rose
69 and 51 mm.

The carotid remaining undamped, the chorda was stimulated during the
third minute. It caused a rise of saliva of 203 mm.

The effect of diminished blood supply upon the percentage composition
of saliva has not been very fully investigated. But Eckhard ^ states that
ligature of the veins of the submaxillary gland does not cause chorda
saliva to alter its character and become like sympathetic saliva. And,
according to Heidenhain,^ diminution of the blood supply by compression
of the carotid does not cause an appreciable increase in the percentage of
solids in saliva.

Heidenhain's experiments undoubtedly show that, in certain circum-
stances, a diminution of the blood supply to the gland has no considerable
influence upon the percentage of organic substance in the saliva, obtained
by stimulating the cranial nerve. But this does not seem to me to hold
in all circumstances, for, in some observations on the submaxillary
gland of the dog, made by Fletcher and myself,'^ bleeding the animal,
whilst decreasing the rate of the secretion of saliva produced by
pilocarpine, largely increased the percentage of organic substance in the

^ Stud. d. physiol. Inst, zu Breslau, Leipzig, S. 93.

2 Beitr. z. Anat. u. Physiol. [Eckhard), Giessen, 1860, Bd. ii. S. 212.

3 Arch.f. d. ges. Physiol., Bonn, 1878, Bd. xvii. S. 33, 43.
'^ Phil. Trans., London, 1889, vol. clxxx. p. 131.


There are no experiments which show definitely what is the effect on
the percentage composition of saliva of a decrease of blood supply due
to simple constriction of the vessels. When the cranial nerve is
stimulated during compression of the carotid artery, the blood flowing
through the gland flows through dilated vessels. When the diminution
in blood supply is brought about by stimulating a vaso-constrictor
nerve, the blood flowing through the gland flows through constricted
vessels. It is probable that, in the former case, fluid passes more
readily through the vessel walls ; hence, with the same amount of
organic substance secreted in the two cases, one saliva might have a
low and the other a high percentage of organic substance.

Changes in the amount and character of the saliva ^ may, however,
be produced by variations in the character of the blood. The injection
of a considerable quantity of dilute salt solution, such as 0*2 per cent., lea-ds
to a considerable increase m the rate of secretion of saliva, whether this
is set up by stimulating the chorda tympani or by injecting small
quantities of pilocarpine. Up to a certain point the percentage of
salts increases in the normal manner; beyond this the percentage ceases
to increase and may fall. An increase in rate may also be produced by in-
jecting into the blood 100 c.c. to 250 c.c. of stronger solution (as 2 per cent.)
of sodium chloride or sodium carbonate. Probably this amount leads to
the passage of water from the tissues, and so increases the volume of the
blood. The injection may cause an increase in the percentage of salts.
Injection of strong salt solution into the blood, in quantity sufficient to
increase the percentage of sodium chloride in the serum, was found by
Xovi - to increase the percentage of the salt in submaxillary saliva ;
though never up to that in the serum. When a certain amount of strong
salt solution (20 per cent.) is mjected, the gland becomes oedematous,
and neither placing acids on the tongue (Novi), nor stimulating the
chorda tympani, nor injecting pilocarpine (Langley and Fletcher), will
cause a secretion.

Eelation of Secretion to the Flow of Lymph.

We know very little with regard to the flow of lymph from the
glands in various conditions. The lymph vessels leave the submaxillary
gland at the hilus. If the lymph could be collected and analysed, it
would give information very much needed with regard to the secretory
activity. Heidenhain,^ who has paid some attention to the subject,
appears only to have noticed whether oedema of the gland was produced
or not, but it is manifest that if the lymph vessels were large there
might be very great increase in the lymph flow without oedema.

Heidenhain * considers that there is no increase in lymph flow from
the gland during stimulation of the chorda, either before or after giving
atropine. Supposing, then, that atropine does not act on the vessel wall,
so as to hinder the passage of fluid through it, it would follow that fluid
passes from the vessels in increasing amount, as an increasing amount
of saliva is secreted by the gland. In other words, it would follow that
there is in rest a certain slight constant formation of lymph, and that,

1 Cf. Langley and Fletcher, op. cit.

^Arch.f. Anat. u. Physiol., Leipzig, 1888, Physiol. Abth., S. 403.

^Arch.f. d. ges. Physiol., Bonn, 1874, Bd. ix. S. 346.

4 Hermann's "Handbuch," 1880, Bd. i. Th. 1, S. 73.


when the gland secretes, an additional amount is formed exactly equal
to that of the fluid in the saliva secreted, — a conclusion which it is not
easy to accept.

In two conditions oedema of the gland is obtained : First, when
dilute acid (0'5 per cent. HCl) or an alkaline salt (5 per cent. NagCOg)
is injected into the gland duct.^ In this case, cedema is slowly pro-
duced; rapidly, however, if the chorda tympani he stimulated, though
no secretion follows. There can be little hesitation in attributing this
to the injury inflicted on the walls of the small vessels ; for damage of
the vessels, as we know, largely increases the amount of the lymph
formed in any given condition. Secondly, when there is a considerable
resistance to the flow of saliva from the duct. On continued stimulation
of the chorda in such cases, the lobules become separated by a mucous
fluid, and there is great oedema. At first this fluid consists simply of
filtered saliva ; later, probably, lymph is added, partly in consequence of
a direct injury to the vessels, and partly, as suggested by Heidenhain, in
consequence of pressure on the vein.

The Seceetory Pressure.

Ludwig 2 was the first to show, by experiment on the submaxillary
gland of the dog, that the secretory pressure may overpass considerably
the blood pressure. Thus in one case he obtained a pressure of 190 mm.
of mercury from the saliva caused to flow by stimulating the chordo-
lingual nerve, although the blood pressure in the carotid artery was only
112 mm. of mercury. Since that time considerably higher pressures
have been obtained from chorda saliva ; the maximum pressure observ-
able in any one species is, broadly speaking, the greater, the larger the

On connecting Wharton's duct with a mercurial manometer, and
stimulating the chorda tympani, the pressure rises at first rapidly, then
more and more slowly ; when the maximum pressure is attained, a
cessation of the stimulus is followed by a fall of pressure, due to filtra-
tion taking place between the cells of the ducts and of the alveoli.
When the observation is at all frequently repeated, the lobules of the
gland become separated by mucous fluid, the pressure attained becomes
less, and the irritability of the gland greatly decreases.

In the parotid gland of the dog, the observed secretory pressure is
less than in the submaxillary gland, usually being 100 to 130 mm. of
mercury, but the difference is probably due to the limpidity of the
parotid saliva, which allows a more rapid filtration.

The pressure of the sympathetic secretion may also exceed that
of arterial blood. In experimenting with a mercurial manometer, the
pressure should be raised artificially to about 150 mm. of mercury
during the first stimulation of the sympathetic, the connection of the
manometer with Wharton's duct clamped for about thirty seconds,
and then undamped and the sympathetic again stimulated. Heiden-
hain,^ in an experiment on the submaxillary gland of a dog, found
that the sympathetic saliva was secreted at a pressure of 150 to 160
mm., whilst the pressure of the chorda saliva was 250 to 270 mm.

^ Gianuzzi, Ber. d. k. sacks. Gesellsch. d. WissenscTi. , 1865.
IZtschr.f. rat. Med., 1851, N. F., Bd. i. S. 271.
^ Stud. d. physiol. Inst, zu Breslau, Leipzig, S. 69.


It may, however, be doubted whether there is such a difference in the
maximum pressure. In the observations I have made on the point,
stimulating alternately the chorda tympani and the sympathetic, the
sympathetic has given a perceptible though slight and brief rise of
pressure at approximately the maximum pressure obtainable from the
chorda tympani.

Eeflex Inhibition of the Salivary Seceetion.

During the progress of secretion, a certain decrease in the rate of
flow, or even a cessation, may be caused by stimulation of afferent
nerves. Such an effect might be due — to select the most probable
causes — either to an inhibition of the central secretory centre, or to a
constriction of the blood vessels of the gland. The experiments have
not, however, been directed to an accurate determination of the method
of production of reflex inhibition.

Pawlow ^ states that the slow secretion induced by partial dyspnoea,
or by curari, is decreased or temporarily stopped by stimulation of the
sciatic for one or two minutes with a particular strength of current, or
by exposure of the abdominal viscera. The experiments given can
hardly be considered to be conclusive, and Buff^ finds that, quite apart
from stimulation, the secretion occurring in the conditions of Pawlow's
experiments is not itself constant in rate.

Action of Alkaloids upon the Salivary Glands.

There are obviously a number of ways in which a substance intro-
duced into the blood might cause a secretion of saliva. It might
stimulate the peripheral endings of sensory nerves and produce a reflex
secretion ; it might stimulate some part of the central nervous system,
the connections of the visceral nerve-fibres with the local nerve-cells,
the nerve-cells directly, the nerve-endings in the gland, or finally the
gland-cells directly. Of several of these modes of action we have no
certain example. We shall confine our attention to those alkaloids,
the effects of which have most served as a basis of physiological

Atropine. —Atropine arrests the normal secretion from the glands
of the mouth, nose, and pharnyx, so that the whole mucous membrane
becomes dry. The arrest is due to a paralysis of the cranial secretory
nerves, the strongest stimulation of them no longer causing a secretion.*
In the dog, 10 to 15 mgrms. of atropine, when injected into a vein, pro-
duce the paralysis ; in the cat, 3 to 5 mgrms. are sufficient. Considerably
smaller doses than these reduce to very small limits the secretory power
of the nerves ; hence, in determining the minimal amount of atropine
required to produce paralysis, it is advisable to stimulate the nerve for
a minute or more, and to repeat this after a few minutes' interval.

The sympathetic nerve is either not paralysed at all, or only by a

^ Arch. f. d. ges. Physiol., Bonn, 1878, Bd. xvi. S. 272 (experiments made on the sub-
maxillary gland of the dog).

"^ Bcitr. z. Anat. u. Physiol. (Hckhard), Giessen, 1888, Bd. xii. S. 3.

' A few only of the original pajjers dealing with this subject can be given here ; fuller
references will be found in treatises on pharmacology.

^ Keuchel, "Das Atropin und die Hemniungsnerven," Dorpat, 1868; Heidenhain,
Arch./, d. ges. Physiol., Bonn, 1872, Bd. v. S. 309.


comparatively large dose of atropine.^ In the clog more than 100
mgrms. may Ije injected into a vein, and still secretion will be obtained
from the submaxillary gland Ijy stimulating the cervical sympathetic.
In the cat this nerve ceases to cause a secretion after aV)Out 30 mgrms.
of atropine have been given.-

The point of action of atropine is the termination of the nerve-fibres
around the gland-cells. There are several facts which show this. We
may mention the following : — In the case of the submaxillary gland,
when a dose of atropine has been given just sufficient to paralyse the
chorda tympani, no secretion is oJjtained by stimulating peripherally of
the (true) sul)maxillary ganglion ; i.e., the postganglionic nerve-filjres
cause no secretion. Atropine applied directly to nerve-fibres — whether
preganglionic or postganglionic — in their course towards a tissue, does
not paralyse them. The paralysis produced by it must then be either
one of nerve-endings or of gland-cells. But in the case we are consider-
ing the gland-cells are not paralysed, since they are at once set secreting
by stimulating the cervical sympathetic. Hence we conclude that
atropine acts upon and paralyses the nerve-endings of the postganglionic
secretory fibres of the chorda tympani. And we may conclude, further,
that in other cases in which atropine paralyses secretory nerves, it has
this effect in consequence of an action upon the nerve-endings in the

The exact method of action of atropine we can only guess at ; Ave might
suppose, either that it annuls the conductivity of the nerve-endings, or that
it causes a retraction of the terminal filaments, in the manner suggested by
Duval and others for the processes of nerve-cehs in general, so that nervous
impulses can no longer pass from the nerve-endings to the gland-cells.

Atropine does not paralyse the vaso-dilator fibres which accompany
the cranial secretory nerves. This was first shown by Heidenhain ^ in
the case of the chorda tympani of the dog. It is true that, when large
doses of atropine are given, both vaso-dilator and vaso-constrictor glandular
nerves produce less effect than normal, but there is nothing to show that
this action is in any way specific.

Pilocarpine and mtiscarine.— Both pilocarpine and muscarine pro-
duce copious and prolonged secretion, when given in very small quantity ;
for example, when 1 or 2 mgrms. are injected into the blood.^ The
secretion when it slackens is increased by a further dose of the alkaloid,
so that the flow of saliva can be kept up for a very long time, apparently
indefinitely. A large dose is not required in order to produce the
maximum rate of flow, its effect is rather to increase the duration of the
flow. The saliva obtained is like that produced by stimulating the
cerebral nerve, and the secretion is accompanied by a great dilation of
the vessels of the gland.

The secretion to which these alkaloids give rise from the submaxillary
gland is unaffected by section of the chorda tympani, or by extirpation
of the superior cervical ganglion ; it occurs after the connections of the
chorda tympani with the local nerve-cells have been paralysed by

1 Heidenhain, op. cit.

" Langley, Journ. Physiol., Cambridge, 1878, vol. i. p. 98.
^ Op. cit., supra.

* The chief features of the action of muscarine were described, " Das Muscarin," Leipzig,
by Schmiedeberg u. Koppe in 1869.

VOL. I.— 33


nicotine, and also after degeneration of the chorda tympani itself (cf.
p. 519). The alkaloids therefore stimulate some peripheral structure.
And as in the case of atropine, so with pilocarpine and muscarine, it is
hardly open to doubt that the nerve-endings of the postganglionic fibres
are the points of attack. The nerve-endings of the sympathetic nerve-
fibres, on the other hand, are not stimulated by pilocarpine or by

Stimulation of the chorda tympani during the pilocarpine secretion "^
produces in most circumstances an increase in the rate of flow, but wdien
the secretion is as rapid, or nearly as rapid, as the alkaloid is capable
of producing, the chorda has little or no effect. Further, after large
doses of pilocarpine have been given, the chorda has also little or no
effect ; in the latter case, the apparent paralysing action may be due
to the presence of more than one alkaloid in what passes for pilo-

Stimulation of the sympathetic during the pilocarpine secretion
causes a primary increase in rate, like that of the augmented secretion ;
after this there is a slowing, and if the stimulation be strong, there may
be a complete cessation of the flow. The slowing effect is less in the
submaxillary gland of the cat than in that of the dog, and less in the
submaxillary of the dog than in the parotid of the dog.

The effect of the sympathetic in the last two cases is seen in the following
extract from an experiment : ^ —

Dog. — Pilocarpine Nitrate injected — Rise of Saliva in Tubes connected loith the
Ducts of the Submaxillary and Parotid Glands, taken every thirty seconds,
in millimetres.

Submaxillary . 25 54 9 3 2 1 1 3 11 19 29 32 32
Parotid . ,5920000000000122

stim. sympathetic

The mutual antagonism'^ of atropine and pilocarpine (or mus-
carine). — If atropine, in quantity just sufficient to paralyse the chorda
tympani, be injected into a vein of an animal, subsequent injection of
pilocarpine or muscarine may or may not cause secretion. In many
cases, as the amount of the alkaloid given is increased, death ensues,
whilst the secretory nerves are still paralysed by atropine.

There two methods by which the antagonistic action of two
poisons on the salivary glands may be observed more satisfactorily
than by injecting them both into the general circulation. The one is
to inject the weaker poison in such a way that it passes through the
vessels of the gland without entering the general circulation. The
other method is to inject a small quantity of a rather strong solution
of the weaker poison into the gland duct. In either case, the stronger
poison is injected into the general circulation.

1 Langley, Journ. Anat. and Physiol., London, 1876, vol. xi. p. 173 ; Journ. Physiol.,
Cambridge and London, 1878, vol. i. p. 339 ; Gley, ArcJi. cle x>hysiol. norm, et path., Paris,
1889, p. 151.

- Langley, Journ. Physiol., Cambridge and London, 1889, vol. x. p. 826.

^ For the action of pliysostigmine and its antagonistic action on atropine, cf. Heidenhain,
Arch. f. d. ges. Physiol., Bonn, 1872, Bd. v. S. 309, and 1874, Bd. ix. S. 335. For the
mutual antagonism of poisons in general, and especially as regards muscarine and atropine,
cf. Provost, Arch, de physiol. norm, et jwih., Paris, 1877, p. 801.


I have tried both methods ^ in observations on the effects of
f)ilocarpine and atropine upon the submaxillary gland of the cat and
dog. The latter method is much simpler, and seems to me better. An
experiment, briefly stated, is as follows. A paralysing dose of atropine
is injected into a body vein. A cannula filled with a 2 to 4 per cent,
solution of pilocarpine nitrate is tied into Wliarton's duct, and O'l to 0"25
per cent, of the solution driven into the gland. This causes a secretion
of saliva and great increase of blood flow, lasting several minutes, but
steadily lessening in rate. During the flow of saliva the chorda
tympani becomes again irritable, and may remain so for a short time
after pilocarpine has ceased to produce a secretion. As the pilocarpine
is carried out of the gland by the secretion, by the blood, and by the
lymph, the atropine continually flowing to the gland in the blood again
acquires the upper hand, and the nerve -endings become again paralysed.
With renewed injection of pilocarpine there is renewed transient secre-
tion and renewed transient irritability of the chorda tympani. And
the paralysis and recovery may be repeated many times in an hour.
It is, however, to be noticed, that if more than the minimal dose of
atropine be given, more than one injection of pilocarpine may be required.

Although pilocarpine can instantaneously restore some degree of activity to
the chorda tympani which has been paralysed by atropine, yet the activity is
always considerably less than normal.

In the cat, when the cervical sympathetic has been paralysed by atropine,
its activity can be restored by injecting pilocarpine into the duct, although
pilocarpine does not stimulate the secretory nerve endings of the sympathetic.

Nicotine. — Nicotine causes a brief flow of saliva, followed by a
temporary paralysis of the cranial and sympathetic fibres ^ up to their
connections with the peripheral ganglia.^ We have already described the
main features of this paralysis in connection with the chorda tympani,
and in connection with the sympathetic (p. 480). In all the mammals
which have been experimented on, small doses of nicotine readily pro-
duce excitatory effects, but the amount required to paralyse the secretory
and vasomotor preganglionic fibres varies widely in different cases.
Moreover, the minimal amount required to produce paralysis is not
precisely the same for fibres of different origin, or for fibres of similar
origin but different function. In the rabbit and cat the differences are
not great, the amount required varying from about 5 to about 10 mgrms.
In these animals about 10 mgrms. of nicotine injected into the blood
will cause a paralysis of preganglionic fibres lasting about fifteen
minutes. In the dog, 30 to 40 mgrms. have a similar effect on the chorda
tympani, in so far that, usually, stimulation of the chorda for about twenty
seconds causes no secretion ; but in some cases, at any rate, and even
after larger doses, more protracted stimulation of the chorda induces
gradually an active and protracted secretion,* continuing for some time
after the cessation of the stimulus. And very large doses may be
given to a dog without paralysing completely the cervical sympathetic.

^ Journ. Anat. and Physiol., London, 1876, vol. xi. p. 173 ; Journ. Physiol., Cam-
bridge and London, 1878, vol. i. p. 339 ; 1880, vol. iii. p. 2. For method of injecting into
tlie gland arteries, of. Heidenhain, op. cit., 1874.

- Heidenhain, Arch. f. d. gas. Physiol., Bonn, 1872, Bd. v. S. 316.

^ Langley and Dickinson, Proc. Roy. Soc. London, 1889, vol. xvi. p. 423 ; Langley,
Journ. PJiysiol., Cambridge and London, 1890, vol. xi. p. 123.

^ Repeated doses have a tendency to cause in the dog a continuous secretion.


On the hypothesis that nicotine causes a contraction of the terminal
fibrils of the chorda tympani, we might suppose that protracted stimulation
leads to a slow gradual extension of the terminal fibrils, so that nervous
impulses passing down the chorda tympani can again set up impulses in the
peripheral nerve-cells.


The rapid flow of saliva caused by stimidating the chorda tympani
suggested, not unnaturally, that a considerable formation of heat must
take place in the submaxillary gland. Ludwig and Spiess,^ using thermo-
electric junctions, and Ludwig,^ using thermometers specially designed,
brought experimental proof that in the dog this was in fact the case.

Ludwig and Spiess placed one junction in the carotid artery,
arranged as in the method of determining lateral blood pressure, so
that the actual junction was, they said, in the full blood stream. The
other junction was placed in a cannula connected with Wharton's
duct, and apparently on the same side as that of the carotid taken.
With a moderate rate of secretion they found the saliva to be about
1° C. warmer than the blood in the carotid.

Ludwig placed one thermometer in the carotid near its origin, and
another in the course of a cannula connected with Wharton's duct of the
opposite side. He states that there was in no case clotting in the
carotid, but there does not seem to have been a flow of blood around the
bulb of the thermometer. The room was kept at a temperature not
less than 24° C. The saliva was found to be constantly of a higher
temperature than the blood. The extent of this varied in different
experiments, and, generally speaking, was greater the faster the secretion.

Online LibraryE. A. (Edward Albert) Sharpey-SchäferText-book of physiology; (Volume v.1) → online text (page 73 of 147)