NEURAL REGULATION OF THE BIOCHEMICAL PROCESSES OF NERVE ACTIVITY (ACTIVITY OF CHOLINESTERASE)

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• Collection: General CIA Records
• Document Number (FOIA) /ESDN (CREST): CIA-RDP80-00809A000700180333-1
• Release Decision: RIPPUB
• Original Classification: U
• Document Page Count: 7
• Document Creation Date: December 22, 2016
• Document Release Date: September 6, 2011
• Sequence Number: 333
• Publication Date: May 24, 1954
• Content Type: REPORT

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By N. F. Baranova, Ye. N. Spersnskaya
Lab of Nerve Regulation of Endocrine Functions,
Inst of Physiol im. I. P. Pavlov, Acad Sci USSR
Clinical +tudy of human endocrine diseases and laboratory observations of
anima~s~ #jie functions -gf~y~fos~,endno~jne g],ap?s have been ezper3menf,~il~y die-
rvpCed, always offord'clearly_~define~'?avide~e Qj'~s?-diattabt;tite~ tii2_?ti~yous.
system. These nervous disturbances are frequently- the -primary factor com.
palling a patient to consult a physici~:n. Functional disorderr,-.?of.,bhe
nervous system affect all the branches of the system, and may, be_,.
made manifest in various ,ways; ipsomnia, a general sate of excite-
went, somnolence, apathy ~inab111ty to concentrate various ~isturbancea
of the digestive tract, s~Cin diseases, and regulatory 'disturbances in the
cardiovascular system and other physiolo~icai systems of the organism. These
phenomena, which are connected with functional disorders of the nervous system,
are peculiar, lr. many of their r.,anifestations, to aumercus endocrine disorders.
This attracted our attention, and prompted our laboratory many years ago to
undertake the study of the problem involved in the neural regulation of physi-
ological functions in cases of endocrine imbalance.
Endocrine disturbances ::ause marke3 chances in the internal environment of
an organism. The unusual complexity of this problem caused us to include in
our study of the physiologicsl mechanisms an investigation of intimate bio
chemical processes connected with the functions of the nervous system. This
article deals with some of the data obtained in our research.
All the functions of an organism, the entire "internal world" of animals
and men, is under the constant regulatory in?'luence of Lhe higher divisions of
the central nervous system, i.e., the _erebral cortex. I. P. Pavlov formulated
this postulate in the following way, "This hi:rher divisions control all file
phenomena occurring in the body. ... The more perfect the central nervous system
of an animal organism is, ti:e more ceuiralized it is, and the more does its
higher division determine and define the entire activity of the o(?ganiam'~
(Ref 1, 1935, pp 409-410).
Impulses arising in tt,e internal orgnns of an organism are exceptionally
important to the functional condition and constant toms of the cerebral cortex.
"These irritations arisin in the internal organs, even though 'we may not be
aware of them, nevertheless constantly maintain the high toms of the cerebrum"
(Ref 1, 1935 p 421),
Concomitant with the study of the inr,errelationships between an organism
and its external envii?omnent, the problem of the processes occurring within the
orgsnism itself was ever present in the mind of I. P. Pavlov. He wrote: "In
the cortex, together witi, a grandiose representation of the outs~~lt?.world
through the afferent fibers (and this is an essential condition of the higher
regulatory functions), there is also a wide representation of the internal
world of an organism, i.e. the operational condition of the mass of organs and
tissues, and the mass of internal organic processes " (Ref 1, 1932, p 140).
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The problem of the ei'fect of an irritation which arises In nn internal or-
gan and affects the activity of the cerebrum has been thoroughly elaborated by
K. M. Bykov and his associates(2). Their efforts also show the important role
of the humoral factor and of the hormonal activities of the endocrine glands in
the cortical process which regulates the functions of the internal organs. The
works of Balakehinn (3 ), Bykov and Alekseyev-Berkman(?), Kel'man (4), O1'yanskaya
(>), and others also demonstrate the participation of the endocrine glands (the
hypophsic, the suprarenal, and the thyroid)in the process by which the cerebral
cortex regulates the activity of the internal organs and of the various tissue
pro::esses.
A cessation or disturbance of the functions of the endocrine glands dis?
rupts the operation of all branches of the cerebral nervous system, and prima-
rily that of its higher divisions. Associates of I. Y. Pavlov made numerous
observations in this i'ield. For a review of this work see A. G. Ivanov-Smo-
lenskiy (E),
Insofar as all nerve processes are based essentially on a physicochemical
mechanism, disturbances in the nerve process observed in cases of endocrine im-
balance are likewise based on changes in the physicochemical reactions occur-
ring in tine organisms. This assumption vas frequently emphasized by I. P. ~av-
low in a number of his works. In one of them, he wrote, "It is self-evident
that besides such particular questions regarding disturbances of normal nerve
activity, another problem still faces physiolosists, the problem of the physi-
ochemical mechanism of the most elecentary processes: irritation and in-
hibition and their interrelationships and overstrains" (1).
The physicochemical processes taking place in nerve tissues include the
humoral link, which is .active Suring the transmission of a nerve impulse. The
concept of the humoral link, as we understand it, includes mediators (acethyl-
choline, sympathin) released by the activity of the nervous system, products of
metabolism occurring in the nerve tissues and in the innervated organs and tis-
sues, and hormones from the endocrine glands. The importance of the vitamins
which participate in the complicated biochemical reactions involved in nerve
stimulation must not be for,zor,ten. Thu;, for example, Vitamin Bl is an indis-
pensable component ~f carbehydrnt? metsbolism, i.e., of n series of processes
which play nn important part in the activity of the nervous system at all of
its levels.
In our research we proceeded from the assumption that whenever disturbances
of endocrine activity take place, which always produce ci~anges in the functional
condition of nil divisions of the nervous system, including that of the cerebral
cortex, changes in physicochemical processes occur, One of the components of
the complicated an3 munerous biochemical processes is n^.ethylcholine metabolism,
which actively participates in trio operation of the nervous process.
The works of our laboratory which have already been publishe3 (G, 7, 10)
indicate that in various pathological conditions, Including endocrine disturb-
ances, the liberation of mediators (sympathin or acetylcholine-like substances)
occurs in amounts qualitatively and quantitatively capable of producing a re-
action corresponding to tha` induced by the,,aiven mediator In a norma_ organ of
a normal organism. These phenomena occur at the level of the terminal ends of
the vegetative nerve fibers, notwithstanding inversion of the effect or absence
of an effect on the organ upon irritation of these fibers. In an organism in
which pathological conditions exist, i.e., intoxocstion or functional disorders
of the endocrine glands due, for example, to the removal of the hypophysis or
the suprarenal glands, the irritation of the nerve conductors may produce either
no reaction on the part of the organ, or an inverse effect.
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The data in this arts^_le concern the problem of clarifying '.he changes in
the activity of the enzyme which decomposes ncetycholine in an organism, i.e
cholinesterase. ;Je consider it
.,
essential to clarify the nerve mechanism which
regulates the activity of cholinesterase, whi,:h, together with the other enzymes
and biochemical components of nerve activity; participates in the intimate re-
actions that bring about the nervous processes. In one series of experiments
we studied the effect of the irritation of nerve fibers on the activity of cho-
linesterase present in the tissues of organs. In another series we traced the
effect of the severing of n nerve and of its consequent degeneration on the
activity of the cholinesternse present in tissues of the same organs. In a
third series of experiments we determined the role of endocrine factors in the
neural regulation of cholinesterase activity.
The research was conducted at various times of the year using frogs. p
detailed account of the experiments r; -iven in the works of Baranovs
order to determine the effect of irritation of the nervous system on the)activ-
ity of cholinesterase, we irritated the vegetative nerve fibers which innervate
various organs. ~Je observed the effects of irritation of the sympathetic and
parasympathetic nerve fibers t2:at innervate *.he liver, and of the sympathetic
fibers of skeletal muscles which were ir. n tonic or tetar.ic state. For these
experiments, we used the forearm and rural muscles of a frog. Research was
also done on the activity of cholinesterase in cases where there was complete
denervation of these muscles.
Experimental ir.?itatior. of the sympathetic nerve fibers of the liver either
increased or decreased the activity of cholinesterase. Similar changes were
also observed when the parasympathetic nerve fibers were irritated. These
changes, however, were less uronounc?:, and showed a tendency toward a decrease
in activity (Fig 1).
Irritation of the parasympathetic nerve fibers which innervate the skeletal
however, awe~ecconsiderablyhlessJintenhiveothanyYhosetobserved when the shanges
the tic fiber.: which innervate the liver were irritated. The activity ofycho-
linesterase in groups of skeletal muscles with differing functions showed var-
ious changes. In the muscles of a fror's forearm, which may also function as
tonic muscles in connection with the seasonal change in metabolism during
spring !;ime, the activity of cF.clinesterase changed considerably when the nerve
fibers were irritated. Rowever, in the rural muscles, whose function remains
the same during all seasons, the activit;,? of the enzyme showed little varia-
tion (Fig 2),
It should be noted that the cholinesterase activity in these functionally
different groups of skeletal musclee varies even without irritation of the
sympathetic nerve fibers which innervate them. In a series oi' experiments in
which we compared the activity of eholinerterase in the muscles of the forearm
(functioning in :he spring as a tonic-type mu^?
in tare st;ai.ch`, muscler: of t`.:e nblo;aer. (~.o.:ic) and ~our:~._4muscles((tetani,~?and
our? obse_va';ions revealed that this activity was no~.reciably higher in tonic
muscles theme in tetanic muscles, nc~n3c; in the activity of eholinestersse in
tetnnir_ muscles were observed more coral;;. such ch:-n,ces i:ere relatively in-
si~nificnnt in me,gnitude. -
In order tc determine tt,e role of the motor nerves in the regulation of
the activity of cholinesterase, we observed the activity of this enzyme in the
totally denervated forearm and rural muscles of ^r. animal (fror.) and compared
it with the activity in the rams muscles of normal extremities of the same
nnim:zl. The majority of experiments showed a slight decrease in the activity
of cholinesterase in a denervated extremity as comm~red with this activity in
the normal extremity used as r control. These changes were eepressed some-
what more definitely in the muscles of the forearm than in the rural muscles.
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changes under the influence of ?? c 13~ ``te aver and the skeletal musculature
bers. These impulses may csuseirppideshiftssin+the activityegftthevenxymee fi-
In contrast to the rapid emergen~~y readjustments produced in an organism
by nerve impulses, the hormones secreted by +.he endccri::e glands us a result
of the action of the nervous system, espec?ia11y the cerebal cortex, also pro-
duce functional readJustments of the organs and tissues. These readJustments,
however, occur much more slowly. +le observed the regular character oi' such
changes in relation to cholinesterase activity. These changes definitely occur
during endocrine disturbances, and not only in pathological conditions of an
orgsnism; they can be essily detected in normal frogs during the seasonal re-
udJustment of metabolism, especially during the spring.
Our experiments Show that the acrivity cf cholinesterase in the liver of
normal frngg during the spring is cons:derubiy lower than that in the muscles
of the forearm, while Sn the fall, it is higher. This may be explained by the
frog's winter periods of starvation, which csuse a sharp decrease in the gly-
cogen content of its liver.
The importance of carbohydrate metabolism for the acetylchol'.:e metabolism
has been established by a series of experiments. Changes in activity which de-
pend on d'_fferent concentrations of glucose hsve been observed during experi-
ments in our laboratory both in vitro and Sn vivo.
Our next task was to trace the changes occurring in the activity of choline-
sterase in the liver and skeletal musculature after the removal of certain en-
docrine glands. In 1947 in our laboratory, I. M. Dzhakson (9) determined that
the ability of the liver to destroy acetylcholine was decreased by the removal
of the hypophysls. Further research demonstrated that this ability was due to
the presence of cholinesterase in the liver, and that the activity of this en-
zyme changed in accordance with the functional state of the entire organism,
particularly the liver.
Since the suprarenal glands, especially their cortex, influence all types
of metabolism, including carbohydrate and salt metabolism, we assumed that the
removal of the suprarenal glands would be reflected in the activity of choline-
sterase in the liver and the skeletal muscles of sn animal. We based this as-
sumption on the data elaborated abov?, which demonstrate the connuction between
the functional state of an organ and its acetylcholine metabolism. In fact,
after we hsd removed the suprarenal glands of a frog, we observed a considerable
change in the activity of cholinesterase in the liver and skeletal musculature.
The activity of cholinesterase in the liver in the m?,jority of experiments
showed a considerable decrease, as compared to the liver of normal frogs, and
the activity of cholinesterase in various groups of skeletal muscles decreased
more in tonic muscles than in tetanic muscles. The skeletal muscles which are
sub,Ject to more marked functional r_hanes during the seasonal readJustments of
their metabolism, i.e., the muscles of the frog's forea:?m, also undergo essen-
tial changes (frequently a decrease) in the activity of cholinesterase after
the removal of the suprarenal glands.
We slso observed the sbove relationships in experiments on wa*m_blooded
animals, i.e., rats whose suprarenal glands had been removed.
Irritation of the sympathetic and parasympathetic nerve fibers which in-
nervate the liver, and of the sympathetic fibers leading to the skeletal mus-
cles, does trot produce any change in the activity of cholinesterase in animals
whose suprarenal glands have been removed. The slight changes in this activity
in the skeletal muscles of such ani.^4:1s after the total denervation of these
muscles are even less pronounced.
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Consequently, where a chlnaP in the acetylcholine metabolism has occurred,
as noted in animals whose adrenal cortex is deficient, nerve impulses trans-
mitted by the central nervous system through vegetative and motor nerve Pibers
cannot elicit the reaction which usually occurs in normal anivals, i.e., they
do not produce changes in the activity of cholinesterase.
The observations which we have made concern only one small link in the long
chain of chemical processes which occur in the course of activity concomitant to
the transmission oP a nerve impulse, i.e., thP?, pert+aln .nly to activity of the
workinwthis Pieldoand Inethecnearnfuturehiuten~a tompresentrexperimental data
which will bring us closer to nn understanding of the manner in which endocrine
disorders and other pathological conditions modify the intimate processes of the
nervous system.
AIBLIOGRAPHY
1? I. P. Pavlov, The Physiology of the Hypnotic State of the Dag,
?(K Fisio~ogil 6lpnoticheskogo Sos~oyania Sobaki), Full Co1lGeti'on:af-.
Works, Vol _3, Boole 2, Acnd Sci~USSR,~1932; The Neuroses of 'Man and?
Animal (0 Nevrozakh Cheloveka i Zhivotnogo), Sbid., 1935; The Problem
of Sleep (Problems Sna), Sbid.
2? K. M. Bykov, A. I. Alekseyev-Berkman, Formation of Conditioned Reflexes
of Elimination Urea, Comm 1, Pflueg. Arch. f. d. ges. Physiol., Vol
224, Na 5, p 710, 1931; Comm 2, Pflueg. Arch. f,d. ges. Physiol.,Vo1
227, No 3?
3? V. L. Aalakshina, Concerning the Mechanism of Conditioned Reflex Activ-
ity of the Kidneys, Trudy Fiziol Inst LGU, No 17,1936.
4? Kh. B. Kel'man, The Effect of the Cerebral Cortex on the Movements oP
InstSEksen~No~ll Vsesoyuz Inst Eksp, No 5, p 13, 1937; Byulli Vsesoyuz
P, 5, p 13, 1937, Comm 3, Investi~stion of Nerve and Rumoral
Connections (Opyt Issledovaniya Nervno-Cumorsl'nykh Svyazey), Edit by
Acad Bykov, p 7.
5? R. P. O1'yans;tnya, The Cerebral Cortex and Gas Metabolism (Kota Golov-
nogo Mozgs i Gazoobmen) Acad of Med Sci, Edit by Acad Bykov, 1950.
6. A. G. Ivnnov-Smolenskiy, Outlines of the Pathophysiology of Higher
Nervous Activity (Ocherki Patofiziologii Vysshey Nervnoy Deyatel'nosti),
1952?
7? M. F. Belovintseva, ye. N. Speranskaya, The Effect of Endocrine Glands
on the Production and Action of Mediators of the Vegetative Nervous
System, Comm 4, Byull Eksp Biol i Med, No 26, p 3,
$. N. F. Baranova, Concerning the Decomposition of Acetylcholine Caused
by an Epinephrectomy, Comm Fiziol Zhur USSR, No 36, p 5., 1950.
9? I. M. Dzhakson (Jackson j, The Effect of the Hypophysis on the Decompo-
sition of Acetylcholine by the Liver, Byull Eksp Biol i Med, Vol 23,
No 5, 1947.
10. Ye. N. Spersnskaya, The Effect of Endocrine Glands on the Production
and Action of Mediators of the Vegetative Nervous System, Comm 1, Byull
Eksp Biol i Med, No 10, Vol 3, 1947; The Effect of Endocrine Glands oa
the Functions ofl11the Vegetative Nervous System, Vest Leningrad Univ,
No 3, 1949; ReseArch Trends in Endocrinology and Certain Physiolagical
Experimental Data; Vest Leningrad Univ, No 3?
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Irri~tion
of the
Vague Nerve
Irrigation
of the
Sympathetic
Nerve Fibers
Changes is the activity
of cholinesterase caused
by the irritation of the
vegetative nerve Pibers
which innervate the liver
(in percentages of ex-
periments):
1. Increased activity
2. Decreased activity
3? No change in activity
Forearm
6luscle
Sural
N:uscle
Figure 2. Chances in the activity
of cholinesterase in
skeletal muscles caused
by the irritation of the
sympathetic nerve Pibers
which innervate them (in
percentages of experi-
ments):
- 1. Increased activity
2. Decreased activity
3? No change is activity
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