Acetylcholine and ethylene: do they share similar receptors and biological action?
From chemical point of view acetylcholine (ACh) is a quaternary ammonium salt whose biological importance is connected with its role as a neurotransmitter between neurones and other neurocellular junctions. Earlier we have postulated (Kurchii, 1998) and then confirmed (Kurchii, Kurchii, 2000) that A...
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irk-123456789-73732010-03-30T12:02:16Z Acetylcholine and ethylene: do they share similar receptors and biological action? Kurchii, B.A. From chemical point of view acetylcholine (ACh) is a quaternary ammonium salt whose biological importance is connected with its role as a neurotransmitter between neurones and other neurocellular junctions. Earlier we have postulated (Kurchii, 1998) and then confirmed (Kurchii, Kurchii, 2000) that ACh under influence of physiological solution and alkaline mixture was decomposed with releasing of ethylene. Unfortunately using gas chromatograph we could not detected another two peaks on the chromatogram (Kurchii, Kurchii, 2000). Here we identified one of two unknown peaks: it is ethylene oxide. We have revealed that ethylene oxide was released in the quantity much more than ethylene during 10-20 min of decomposition in air or in drop of physiological solution. We have concluded that biological effects of ACh can be caused by action of ethylene oxide that is a very reactive agent and this is a prompt effect for short distance. Ethylene can migrate on the long distance and cause slow effects, but it should be preliminary activated because under normal conditions (temperature and pressure) it is a very inert chemical and cannot react with any substance. Nevertheless, it can be in vivo activated in the free radical addition reactions. Also as follows from our results the question about specific receptors for ACh is questionable. З точки зору хімії ацетилхолін (АХ) є четвертинна амонієва сполука, біологічна роль якої пов’язана з нейропередачею між нейронами та іншими нейроклітинними з’єднаннями. Раніше нами запропоновано (Kurchii, 1998), а потім і підтверджено (Kurchii, Kurchii, 2000), що АХ за дії фізіологічного розчину і лугу розкладався з утворенням етилену. На жаль, ми не змогли визначити два інших піки, отриманих на газовому хроматографі. У цій статті ми ідентифікували один із двох невідомих піків — окис етилену. Встановлено, що окис етилену виділявся в кількості значно більшій за таку ж кількість етилену в атмосфері повітря або в краплі фізіологічного розчину. З’ясовано, що біологічні ефекти ацетилхоліну можуть бути зумовлені дією окису етилену, який є хімічно активною сполукою, і це є швидка його дія на короткі відстані. Етилен же може мігрувати на далекі відстані, спричинюючи сповільнені ефекти, але тільки за умови його активації, бо за нормальних умов (температури і тиску) він є неактивною сполукою і не може вступати в реакції. Проте in vivo етилен може активуватися в реакціях приєднання вільних радикалів. Також, як свідчать здобуті дані, питання про специфічні рецептори АХ залишається дискусійним. 2009 Article Acetylcholine and ethylene: do they share similar receptors and biological action? / B.A. Kurchii // Ukrainica Bioorganica Acta. — 2009. — Т. 7, № 1. — С. 36-44. — Бібліогр.: 75 назв. — англ. 1814-9758 http://dspace.nbuv.gov.ua/handle/123456789/7373 en Інститут молекулярної біології і генетики НАН України |
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From chemical point of view acetylcholine (ACh) is a quaternary ammonium salt whose biological importance is connected with its role as a neurotransmitter between neurones and other neurocellular junctions. Earlier we have postulated (Kurchii, 1998) and then confirmed (Kurchii, Kurchii, 2000) that ACh under influence of physiological solution and alkaline mixture was decomposed with releasing of ethylene. Unfortunately using gas chromatograph we could not detected another two peaks on the chromatogram (Kurchii, Kurchii, 2000). Here we identified one of two unknown peaks: it is ethylene oxide. We have revealed that ethylene oxide was released in the quantity much more than ethylene during 10-20 min of decomposition in air or in drop of physiological solution. We have concluded that biological effects of ACh can be caused by action of ethylene oxide that is a very reactive agent and this is a prompt effect for short distance. Ethylene can migrate on the long distance and cause slow effects, but it should be preliminary activated because under normal conditions (temperature and pressure) it is a very inert chemical and cannot react with any substance. Nevertheless, it can be in vivo activated in the free radical addition reactions. Also as follows from our results the question about specific receptors for ACh is questionable. |
| format |
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| author |
Kurchii, B.A. |
| spellingShingle |
Kurchii, B.A. Acetylcholine and ethylene: do they share similar receptors and biological action? |
| author_facet |
Kurchii, B.A. |
| author_sort |
Kurchii, B.A. |
| title |
Acetylcholine and ethylene: do they share similar receptors and biological action? |
| title_short |
Acetylcholine and ethylene: do they share similar receptors and biological action? |
| title_full |
Acetylcholine and ethylene: do they share similar receptors and biological action? |
| title_fullStr |
Acetylcholine and ethylene: do they share similar receptors and biological action? |
| title_full_unstemmed |
Acetylcholine and ethylene: do they share similar receptors and biological action? |
| title_sort |
acetylcholine and ethylene: do they share similar receptors and biological action? |
| publisher |
Інститут молекулярної біології і генетики НАН України |
| publishDate |
2009 |
| url |
http://dspace.nbuv.gov.ua/handle/123456789/7373 |
| citation_txt |
Acetylcholine and ethylene: do they share similar receptors and biological action? / B.A. Kurchii // Ukrainica Bioorganica Acta. — 2009. — Т. 7, № 1. — С. 36-44. — Бібліогр.: 75 назв. — англ. |
| work_keys_str_mv |
AT kurchiiba acetylcholineandethylenedotheysharesimilarreceptorsandbiologicalaction |
| first_indexed |
2025-07-02T10:11:58Z |
| last_indexed |
2025-07-02T10:11:58Z |
| _version_ |
1836529608203173888 |
| fulltext |
Introduction. Biogenic amine acetylcholine
is a rather simple molecule of formula
(CH3COOCH2CH2N+(CH3)3 [10]. Recent investi�
gations suggest that ACh is not present only in
neurons and glial cells of the nervous system but
also is synthesized in epithelial, mesothelial,
endothelial cells, alveolar macrophage, and
white blood cells [38, 44, 76].
ACh induces conformational changes and
then concomitant cellular changes through their
interactions with membrane�bound proteins. Its
neurophysiological action is mediated by either
nicoticic (nAChR) or muscarinic (mAChR)
receptors. The released ACh by nerve impulse at
the terminal region diffuses across the synaptic
cleft and by binding to protein receptors in the
postsynaptic membrane acts to produce a con�
formational change in the postjunctional mem�
brane of the motor end�plate, providing for an
increase in permeability to cations, especially
Na+ and K+ and this results in a muscle contrac�
tion caused by depolarization of the membrane
of the muscle cell. ACh is enzymatically hydro�
lyzed by acetylcholinesterase in the synaptic
cleft into choline and acetate. Choline is then
transported back into the presynaptic cell and
through the action of acetyltransferase is trans�
formed into ACh [10, 32, 33, 42, 70].
Thus, nAChR converters exstracellular sig�
nals into intracellular effects. In the most cases
the receptors are composed of three functional
parts: a signal receiving (ligand binding) part
"R", effector part "E" that converts signal on to
the inner cell, and part "T", the so�called trans�
ducer that connects "R" and "E" parts (Fig. 1) [38].
36
Acetylcholine and ethylene:
do they share similar receptors and biological action?
B.A. Kurchii*
Institute of Plant Physiology and Genetics, NAS of Ukraine
31/17 Vasylkivska Str., Kyiv, 03022, Ukraine
Summary. From chemical point of view acetylcholine (ACh) is a quaternary ammonium salt whose biological
importance is connected with its role as a neurotransmitter between neurones and other neurocellular junctions.
Earlier we have postulated (Kurchii, 1998) and then confirmed (Kurchii, Kurchii, 2000) that ACh under influ�
ence of physiological solution and alkaline mixture was decomposed with releasing of ethylene. Unfortunately
using gas chromatograph we could not detected another two peaks on the chromatogram (Kurchii, Kurchii,
2000). Here we identified one of two unknown peaks: it is ethylene oxide. We have revealed that ethylene oxide
was released in the quantity much more than ethylene during 10�20 min of decomposition in air or in drop of
physiological solution. We have concluded that biological effects of ACh can be caused by action of ethylene
oxide that is a very reactive agent and this is a prompt effect for short distance. Ethylene can migrate on the long
distance and cause slow effects, but it should be preliminary activated because under normal conditions (tem�
perature and pressure) it is a very inert chemical and cannot react with any substance. Nevertheless, it can be in
vivo activated in the free radical addition reactions. Also as follows from our results the question about specific
receptors for ACh is questionable.
Keywords: acetylcholine, ethylene, ethylene oxide, free radicals, receptors.
www.bioorganica.org.ua
Ukrainica Bioorganica Acta 1 (2009) 36—44
* Corresponding author.
Tel.: +38044�2575160
E�mail address: kurchii@mail.ru
© Б.О. Курчій, 2009
Surprisingly ACh is not only distributed in
vertebrates and invertebrates but also in a plant
kingdom [30, 35, 72]. As in the animals ACh is
synthesized in plants via acetyltransferase (EC
2.3.1.6) [69] and decomposed by acetylcholines�
terase (EC 3.1.1.7) [55, 56]. Little is known about
the role of ACh in the plants. It is proposed that
ACh can act in the plants as a local hormone in
phytochrome�mediated responses [40] and pro�
duces alteration of ion channel activity [33, 35,
72]. Hartmann and Gupta [35] reported data
confirming the existence of ‘ACh�binding sites’
in bean seedlings. However, the biochemical
characteristics of ACh receptors remain unclear
in plants.
It is interestingly to note that from chemical
viewpoint ACh is a quaternary ammonium salt
that theoretically in appropriate conditions can
be decomposed in accordance to Hofmann’s rule
with olefin formation [22, 28, 29]:
If ACh may be decomposed in vivo with ethy�
lene releasing, hence the question on the ACh
receptor still seems to be open. In order to
understand the molecular mechanisms that are
responsible for the biological action of ACh we
have examined the hypothesis [45] that physio�
logical effects of ACh might be attributable to
its decomposition with ethylene formation.
Herein we report an extension of this approach
toward the generation of ethylene and ethylene
oxide from ACh.
Material and methods. The chemicals ACh.HCl
and cholin.HCl used in this work were from
«Mosmedpreparaty». Ethylene oxide was pur�
chased from «Sigma». Chemicals were decom�
posed in 10 cm3 flasks with rubber caps at room
temperature and 1 cm3 of head space gas was
analyzed for ethylene. Ethylene was determined
by a gas chromatograph («Selmihrom», Sumy,
Ukraine) filled with a flame�ionization detector
and a 2 m x 3.2 mm stainless�steel column
packed with Poropack�Q (80�100 mesh). The
oven temperature was 100 °C and the N2, H2 and
O2 (air) flow rates were 40, 40 and 350 ml min�1,
respectively. Ethylene identification was based
on the retention time compared with the C2H4
standard. A computer program was used to cal�
culate the quantities of ethylene in the samples.
Experimental data. Earlier we reported that
ACh.HCl was decomposed to form ethylene [49].
Unfortunately we could not detect two another
peaks. In this work we have identified that one
from the unknown peaks is ethylene oxide
(Fig. 2). Also ethylene oxide was found in the
flasks where to ACh we added several drops of
0,9 NaCl. Ethylene and ethylene oxide were
already found in the flasks after 10 min of expo�
sition. Thus, ACh was decomposed with forma�
tion of ethylene and ethylene oxide. In our expe�
riments the quantity of formed ethylene oxide
was markedly higher than such of ethylene.
Unfortunately we could not detect one peak in
the chromatogram.
Discussion. As mentioned above biological
action of ACh is explained in terms of an inter�
action with receptors for this chemical. This
interaction is believed to be a physicochemical
reaction that depends on the molecule of ACh
Acetylcholine and ethylene: do they share similar receptors and biological action?
37www.bioorganica.org.ua
Signal
R
T
E
Effect
Membrane
Fig. 1. The triune receptor concept (adapted from 38).
H
C
_+
C
N (CH3 ) OH
H2 O ++ N (CH3 ) 3H2 C CH2
Fig. 2. Chromatogram from gas chromatography
analysis of products formed during ACh decompo�
sition. The retention times of the compounds in the
chromatogram are: 39 sec, ethylene; 315 sec, ethy�
lene oxide.
being attracted to a corresponding or a comple�
mentary molecular structure of the receptor.
Two types of ACh receptors are known as asso�
ciated with animal cell membranes mediating
physiological effects of ACh: nicotinic and mus�
carinic, being selectively activated by the ago�
nists nicotine and muscarine, respectively [4, 17,
23]. There are also numerous subtypes of these
receptors.
If hormone perception is necessary for the
coordinated growth and development of multi�
cellular eukaryotes one of the most intriguing
questions is how do the receptors transmit the
signal? In animals it is involved in two distinct
pathways: the nicotinic receptor, in which the
channel is activated directly by acetylcholine,
and the muscarinic receptor, which requires an
indirect G protein�based pathway [25, 27, 65].
NNiiccoottiinniicc RReecceeppttoorrss.. These receptors are
found in both the central nervous system (CNS)
and the peripheral nervous system (PNS) [52].
Nicotinic receptors are divided into the subtypes
nicotinic�N receptors (at ganglionic autonomic
synapses) and nicotinic�M receptors (at neuro�
muscular synapses). Nicotinic�M receptors cause
end�plate depolarization and muscle contrac�
tion, whereas nicotinic�N receptors are involved
in ganglionic transmission [9, 34, 37, 43].
MMuussccaarriinniicc RReecceeppttoorrss.. Five subtypes of mus�
carinic receptors have been identified: M1, M2,
M3, M4, and M5 [26, 39, 50, 53]. M1 receptors are
widespread in the brain, whereas M2 receptors
primarily cluster in the cardiovascular system.
M3 receptors are found mainly in smooth mus�
cles and secretory glands. Much research has
been done to distinguish these sub�types, but
much is stil unfolding. Functions of M4 and M5
are speculative at present. Muscarinic receptors
play a major role in the functioning of the pPNS
and CNS.
It is believed interaction of acetylcholine with
members of the muscarinic receptor family (M1�
M5), which couple to two G proteins: Gi and Gq.
When the Gq�coupled receptors, M1, M3, and
M5, are stimulated, the βγ subunit of Gq dissoci�
ates from the subunits and stimulates phospho�
lipase C�β. Phospholipase C�β in turn hydrolyzes
phosphatidylinositol 4,5�bisphosphate into ino�
sitol 1,4,5�trisphosphate and di�acylglycerol,
both of which activate protein kinase C (PKC).
PKC then activates MAPK by unknown mecha�
nisms. Also mAChRs activates MAPK through
the Gi�coupled receptors [24].
It is suggested that mitogen�activated protein
kinases (MAPKs) are a family of serine/threo�
nine protein kinases that play a crucial role in
transmitting signals from the cell surface to re�
gulate various cellular functions. MAPK is acti�
vated when phosphorylated on both a threonine
and a tyrosine residue [67]; thus, changes in the
phosphorylation state reflect changes in activity
[36, 66]. The mode of signaling that uses this type
of phosphorylation has been referred to as the
two�component system.
EEtthhyylleennee rreecceeppttoorrss.. The plant hormone ethy�
lene is a simple two�carbon (CH2=CH2) gaseous
plant growth regulator that has profound
effects on plant growth and development.
Ethylene is formed from methionine via S�ade�
nosyl�L�methionine (AdoMet) and the cyclic
non�protein amino acid 1�aminocyclopropane�
1�carboxylic acid (ACC). ACC is formed from
AdoMet by the action of ACC synthase (ACS)
and the conversion of ACC to ethylene is carried
out by ACC oxidase (ACO) [1, 44].
This plant growth regulator plays essential
roles in integrating numerous responses to ethy�
lene throughout life of the plant, including pro�
motion of seed germination, induction of ripen�
ing in climacteric fruits, promotion or inhibition
of flowering, leaf and petal abscission, senes�
cence, and plant responses to stresses such as
those induced by pathogens, flooding or drought
[1, 58, 59]. Regulation of ethylene controlled
B.A. Kurchii
38 Ukrainica Bioorganica Acta 1 (2009)
Gi/o
Membrane M2 receptor
Rap 1 GAP II PI3 - kinase
Rap 1 GTR Src
Shc
Grb2 - SOS
Ras
Raf
MEK
ERK 1/2
HEK 293T CNS neurons
Fig. 3. Schematic representation of some pathways
described for the M2 mAChR in various cell lines or
in CNS neurons (adopted from 50).
events can occur at the level of biosynthesis,
catabolism or perception [1, 75]. Although over
the past decade great progress has been made in
the study of biochemical events involved in ethy�
lene:receptor interaction, it is still unclear how
this small organic molecule can influence so
many aspects of plant growth and development.
It is commonly recognized that ethylene may
function as signal molecules that trigger the sig�
nal transduction pathways in cells. It is now
known that eubacteria, archaea, fungi, and
plants also have the two�component system [15].
Ethylene perception is the most well studied in
Arabidopsis and is mediated by a family of five
receptors: ETR1, ERS1, ETR2, ERS2, and EIN4
that have similarity to two�component regulators
from bacteria [6, 7, 16, 20]. Each receptor is most�
ly composed from the four main domains: sensor,
GAF domain (found in cGMP phosphodiesteras�
es, adenylate cyclases and Fh1a transcription
factors), histidine kinase and response regulator
(Fig. 4). The GAF domain is a sequence motif
that has been associated with cyclic nucleotide
binding sites in a variety of proteins [3].
Ethylene signalling pathway contains both
positive and negative regulators. According to
the described models [6, 18] the ethylene recep�
tors activate the kinase activity of CTR1 in the
air (absence of ethylene). CTR1 then actively
suppresses the downstream responses, such that
EIN2 and the EIN3/EIL transcription factors
remain inactive. The binding of ethylene to the
receptor is mediated by a copper cofactor [63].
With ethylene binding mediated by a single cop�
per ion (Cu) the receptors no longer activate
CTR1, and thus CTR1 no longer suppresses the
pathway. This leads to the activation of EIN2,
induction of the transcriptional cascade, and the
establishment of ethylene responses (Fig. 5).
CTR1 is a Raf�like ser/thr kinase with similari�
ty to a mitogen�activated protein kinase kinase
kinase (MAPKKK) (mitogen�activated protein
kinase kinase kinase) [2, 14].
EEtthhyylleennee ooxxiiddee.. Ethylene oxide (EO) is an
agent that reacts easily with cellular substances
such as, for example, deoxyribonucleic acid
(DNA) and proteins, without metabolic activa�
tion [68]. Among the major reaction product in
DNA is N�7(2�hydroxyethyl)guanine, and major
reactive sites in hemoglobin are cysteine, histi�
dine, and in particular N�terminal valine [12].
EO gas is widely used in the sterilization of
medical equipment and materials [13, 73]. EO is
an excellent gas for sterilization, but it also
affects central and peripheral nervous systems
[60�62].
GGeenneerraall mmooddeell ffoorr AACChh aanndd eetthhyylleennee aaccttiioonn iinn
bbiioollooggiiccaall ssyysstteemmss.. Aaccording to the classical
viewpoint of fast «wiring» transmission, the
neurotransmitter is released in the synaptic cleft
at a high concentration (up to 0.3 mM) and brief
pulse (approximately 1 ms), whereas in the «vol�
Acetylcholine and ethylene: do they share similar receptors and biological action?
39www.bioorganica.org.ua
GAF
domainSensor
Response
regulator
Histidine
kinase
Fig. 4. Schematic representation of the arabidopsis
ethylene receptor family (adopted from 6, 20). The
four main domains (sensor, GAF domain, histidine
kinase and response regulator) of the proteins are
indicated.
Nramp
metal
transponter
Unknown
membrane
Ethylene responce
ERF ERF1
EIN3
MAPKK MAPKK
Repress ethylene
responses
CTR1MAPKKK CTR1
ATP
ADP
CH2CH2Air
Ethylene
receptors Cu Cu
ETR1
ETR2
ERS1
ERS2
EIN4
Membrane
MAPK MAPK
EIN2EIN2
EIN3
ERF
transcription
factor
transcription
factor
EIN3/EIL
Fig. 5. Model for ethylene signal transduction
(adapted from 18). In air, ethylene receptors main�
tain CTR1 (it is a Raf�like ser/thr kinase with sim�
ilarity to a mitogen�activated protein kinase kinase
kinase, MAPKKK) in an active state that serves to
repress ethylene responses. Inactivating of CTR1
occurs when ethylene is biding to the receptors.
This leads to activation of EIN2 and initiation of
transcriptional cascade.
ume transmission», lower concentrations of the
neurotransmitter may more slowly reach a dis�
tant target through intercellular space [23]. We
believe that ethylene and ethylene oxide formed
from ACh share different biological effects: 1) a
prompt effect cased by ethylene oxide, and 2) a
longer�lasting effect caused by ethylene.
Experimental data suggest that exogenously
applied labelled ethylene was transformed in
plants to ethylene oxide. Thus, Jerie and Hall
[41] found that ethylene at physiological concen�
tration was metabolized very rapidly to ethylene
oxide. Subsequently Blomstrom and Beyer [8]
demonstrated that in Pisum the earliest detec�
table metabolites were ethylene oxide and its
glucose conjugate. The initial ways for metabo�
lism and action of ethylene were described by
Beyer [5] in the model (Fig. 6), where the first
step is ethylene epoxidation.
Unfortunately as you can see from Fig. 5 and 6
there is some transformation of ideas during last
decades: researchers omitted earlier experimen�
tal data concerning ethylene oxide formation.
Also we believe that transition metals including
copper in the reactive mixture is needed to form
free radicals which then is bound to ethylene.
Transformation of ethylene into reactive sub�
stances in vivo is presented in Fig. 7 [45�48].
There is a little scene of confusion in the biol�
ogy of ethylene: ethylene is not an active sub�
stance under normal temperature and pressure,
and hence, it cannot react with cellular protein�
like substances. Nevertheless there is only one
type of chemical reactions with ethylene: it can
react only with free radicals and thus to form
active structures [28, 57]. Some these reactions
are illustrated in Fig. 7 [45�48].
Reactive agent ethylene oxide does not
require any activation and can act as an initiator
of free chain reactions of many cellular sub�
stances. Several such reactions are presented in
Fig. 8 [46].
From the chemical ethylene oxide properties
also the opening of the ethylene oxide ring can
result in the free radical formation with cellular
substances:
Based on the received experimental data we
have proposed the following mechanism of ACh
and ethylene action (Fig. 9).
The cellular functions of mammalian nervous
systems depend on tight regulation of both
extracellular and intracellular pH. It is shown
that synaptic vesicles have a low pH (about 5.5)
[54] and the buffering capacity of the synaptic
cleft is limited during brief synaptic events [19,
71]. Coreleased with the ACh protons may tran�
B.A. Kurchii
40 Ukrainica Bioorganica Acta 1 (2009)
Conjugate of
ethyleneglycol
( ? )
CO2
Glucose
Ethyleneglycol
H2O[ O ]
O OC C
O O
( ? )
CO2
H2C CH2
[ O ]
H2C CH2
O
Alkilation
CO2
( ? )
OHHO
Receptor
Cu
Receptor
Cu
O
Receptor
Cu
Receptor
Cu
Fig. 6. Hypothetical scheme of initial ways for meta�
bolism and action of ethylene (adapted from 5).
OOHO
.O
2
.
OH HO.
.
R
. .O
+ OH
. R
.
.
.
CH2OH RO+
ROOH
ROO
H2C
.
H2C CH3
.
+
CH2CH2HOOCH2OH
+
.
CH2
H2C
CH2CH2CH2
CH2 CH2
CH2OOCH2
H2OO2CH2H2C
Fig. 7. Possible mechanisms of in vivo ethylene
activation.
RCOOH
RCONH2
H2S
HCN
RCHO
+
+
+
+
+
H2O+
ROH+
H2C
O
CH2
CH2OHCH2HO
CH2 OCORCH2HO
CH CH2ORHO
CH2 CNHOCH2
CH2 SHHOCH2
CH2 NHCORHOCH2
O
RHC
O CH2
CH2
Fig. 8. Possible reactions of ethylene oxide with cel�
lular substances in vivo [46].
O
+ RH2 C CH
2 H
2
C OCH2 R
.
siently change pH in the synaptic cleft. Hence,
rapid and brief pH changes in the synaptic cleft
could modulate synaptic transmission by direct
interaction of protons, for example, with postsy�
naptic receptors. It is believed that approxi�
mately 1 mM ACh is rapidly released into the
cleft, causing nearly synchronous activation of
all of the postsynaptic nAChRs, in approximate�
ly 1 ms. [21]. Nevertheless there is alternative
possibility: releasing of ACh from synaptic vesi�
cles (pH ∼5.5) to synaptic cleft (pH ∼7.4) leads to
ACh decomposition with ethylene oxide and
ethylene formation. Unfortunately the concen�
trations of ACh that activate postsynaptic
AChRs during synaptic events remain unclear.
At the same time some part of the ACh is enzy�
matically hydrolyzed by acetylcholinesterase in
the synaptic cleft to choline and acetate.
Experimental evidences suggest that the
function of the AChR is influenced by its lipid
microenvironment [3]. Ethylene oxide being
very reactive agents may immediately react
with constituents of the postsynaptic mem�
branes causing structural, functional and con�
formational changes in them. For example, it can
react with the membrane enzymes or with the
membrane lipidic phase. In the last case it initi�
ates free radical chain reactions that lead to the
changes in physico�chemical properties of mem�
branes and thus triggers numerous biochemical
and physiological reactions. For example, initia�
tion in the membranes of non�controlled by
antioxidative molecules and enzymatic free radi�
cal chain reactions can lead to destroying in the
lipid/protein interaction and conformational
rearrangements, the opening of sodium chan�
nels, hence depolarization, then muscle contrac�
tion, etc. The disbalance of ions in the compart�
ments of the cell as in the different cells can also
take place. Finally, as you can see from the
scheme the reactions of ACh with cellular sub�
stances occur after ACh activation, i.e. transfor�
mation into reactive forms. Hence, the formation
of ACh/protein complexes may not be a cause
but a consequence of its biological activation.
In conclusion, we would like to stress that the
major finding of this report is that ACh is not
stable substances and under some conditions can
be decomposed in vitro to form ethylene and
ethylene oxide. In this connection we proposed
that complexes ACh (ethylene and ethylene
oxide) with putative receptors are formed after
their biological activation, i.e. transformation in�
to free radical state. Chemicals in the free radi�
cal state may conjugate with any cellular sub�
stance to form complexes with putative recep�
tors that can be reactive or not.
Nevertheless at least one question remains to
be answered. How many receptors can be pre�
sent at the plasmalemma? The question is not
idle. The answers to these questions will provide
important insight not only into the mechanism
activation but also into the molecular mecha�
nisms of action of biologically active substances.
It is believed that about 20 % of all cellular pro�
teins are presented at the membranes of living
cells [51] and this can count approximately
10 000 proteins. Unfortunately the quantity of
plasmalemma proteins is not yet fully known.
Moreover the quantity of these proteins is in
contradiction with information about known
several thousands of natural biologically active
agents. For instance only in the plant kingdom
many tens of thousands of plant bioactive sub�
stances have been identified [11]. Thus, there
are no structural grounds to think that all bio�
logical effects of growth regulating substances
are mediated through protein receptors. In addi�
tion the precise molecular mechanisms underly�
Acetylcholine and ethylene: do they share similar receptors and biological action?
41www.bioorganica.org.ua
CELLULAR MEMBRANE: Initiation of the lipid peroxidation, increasing in the level of free radicals
in the membranes and cytoplasm
Signaling agents
Oxidation of cellular substances, changes in the physico-chemical properties of membranes: destroying
in the lipid/protein interactions, conformational rearrangememts, changes in the rigidity of membranes.
Decomposition of membranes with formation of diverse biologically active substances
Changes in the active and passive
traffic of ions and molecules
through the cellular membranes
Disruption of the
chains of ATP
synthesis
Changes in activities
of membrane-
bonded enzymes
Changes in the activities
of cytoplasmic enzymes
Signaling agents
Disturbance
of current
physiological
functions
Changes in the cellular (cellular compartments) levels of
Ca2+, Cl , K+, Na+, H+, Mg2+ ions. Alteration of the
ion channel activity. Depolarization of membranes
-
CH3
CH3
CH3+
NCH
2
CH
2
O
CCH3C O
Acetylcholine
.
RCH
2CH
2
CH
2
.
CH
2
ROO
CH
2
.
CH
2HO H
2
C
O
CH
2
Conjugation with
cellular substances
Decomposition
to choline and
acetate
Formation of
stable complexes
with putative
receptors
Signaling
pathways
Activation of defence systems including prostaglandins and stress
protein synthesis (signaling agents ), and gene expression
Fig. 9. Schematic mechanisms representing key
steps in acetylcholine and ethylene in vivo activa�
tion and biological action.
ing, for example, nicotinic receptor activation
and as a consequence ligandgated ion channel
activation remain largely unresolved. Hence,
non�receptor mechanisms activation and action
of biologically active agents, including acetyl�
choline, can take place in living systems.
Надійшла в редакцію 13.01.2006 р.
B.A. Kurchii
42 Ukrainica Bioorganica Acta 1 (2009)
Ацетилхолін та етилен: чи подібні їх рецептори й аналогічна біологічна дія?
Б.О. Курчій
Інститут фізіології рослин і генетики НАН України
вул. Васильківська, 31/17, Київ, 03022, Україна
Резюме. З точки зору хімії ацетилхолін (АХ) є четвертинна амонієва сполука, біологічна роль якої пов’язана з
нейропередачею між нейронами та іншими нейроклітинними з’єднаннями. Раніше нами запропоновано (Kurchii,
1998), а потім і підтверджено (Kurchii, Kurchii, 2000), що АХ за дії фізіологічного розчину і лугу розкладався з
утворенням етилену. На жаль, ми не змогли визначити два інших піки, отриманих на газовому хроматографі. У цій
статті ми ідентифікували один із двох невідомих піків — окис етилену. Встановлено, що окис етилену виділявся в
кількості значно більшій за таку ж кількість етилену в атмосфері повітря або в краплі фізіологічного розчину.
З’ясовано, що біологічні ефекти ацетилхоліну можуть бути зумовлені дією окису етилену, який є хімічно актив�
ною сполукою, і це є швидка його дія на короткі відстані. Етилен же може мігрувати на далекі відстані, спричиню�
ючи сповільнені ефекти, але тільки за умови його активації, бо за нормальних умов (температури і тиску) він є не�
активною сполукою і не може вступати в реакції. Проте in vivo етилен може активуватися в реакціях приєднання
вільних радикалів. Також, як свідчать здобуті дані, питання про специфічні рецептори АХ залишається дис�
кусійним.
Ключові слова: ацетилхолін, етилен, окис етилену, вільні радикали, рецептори.
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