|
Gastrointestinal
Melatonin:
Cellular Identification and Biological Role
Abstract
| Introduction
| What
we know about MT?
Extrapineal MT: where and why?
Gut enterochromaffin cells are the main source
of MT in organism
Melatonin
regulates many gut functions
General
conclusions
| References
Igor
M. Kvetnoy,1
Irina E. Ingel,2
Tatiana V. Kvetnaia,1
Nadezhda K. Malinovskaya,3
Semen I. Rapoport,3
Nathan T. Raikhlin,4
Alexander V. Trofimov, 1
& Vadim V. Yuzhakov, 2
1.
Saint-Petersburg Institute of Bioregulation and Gerontology
of the North-West Branch of the Russian Academy of Medical
Sciences, Saint-Petersburg, RUSSIA.
2. Medical Radiological Research Centre of the Russian Academy
of Medical Sciences, Obninsk, RUSSIA.
3. Laboratory of Chronomedicine and Clinical Problems of Gastroenterology
of the Russian Academy of Medical Sciences, Moscow, RUSSIA.
4. Blokhin’s Oncological Research Centre of the Russian
Academy of Medical Sciences, Moscow, RUSSIA.
Submitted:
February 23, 2002
Accepted: February 23, 2002
Key words:
melatonin, enterochromaffin cells, gastrointestinal tract
Abstract
Melatonin,
a pineal hormone, because of its wide activity spectrum, is
a subject of much current interest for biologists and physicians.
It has been demonstrated that pineal gland is not an exclusive
source of melatonin synthesis. Melatonin synthesis has been
found in different sites of the organism, and a major source
of extrapineal melatonin is the gastrointestinal tract. The
role of melatonin in gastrointestinal functions is considered
in the present review.
Introduction
Today
melatonin (MT) is a well-known ubiquitously acting hormone,
a key regulator of biological rhythms. Originally MT was found
in pineal gland in 1958. [1]. During about 20 years after this
discovery it was clearly demonstrated that MT plays a great
role in much vitally important physiological processes, such
as control of biological rhythms, maturing and development of
genitals, pigment metabolism, immune response, metabolism of
free radicals, monitoring of mood and sleep, cell proliferation
and differentiation. Now it has been securely established, that
pineal gland is not an exclusive organ where MT is synthesized.
Extrapineal MT is widespread in the organism of human and animal:
MT-producing cells are found in gastrointestinal tract, airway
epithelium, pancreas, suprarenal glands, thyroid gland, thymus,
urogenital tract, placenta and other organs [2]. Moreover, an
active synthesis of MT has been demonstrated in the non-endocrine
cells, such as mast cells, natural killer cells, eosinophilic
leukocytes, platelets, endothelial cells and others [3]. Such
a wide distribution of MT in the organism determines its key
role as intercellular neuroendocrine regulator and coordinator
of many complex and interrelated biological processes. The highest
content of extrapilneal MT is found in gastrointestinal tract
(GIT): MT level in GIT organs exceeds its nighttime peak in
the pineal gland at 400-fold [4]. Therefore the investigation
of MT is of great importance to gain a better understanding
of its functions and role in organism as a whole.
What
we know about MT?
In
the late 50s a group of American dermatologist A. Lerner from
Yale University identified MT in bovine pineal gland extracts
[1]. A little later MT was found to be 5-methoxy-N-acetylated
derivative of serotonin (N-acetyl-5-methoxytriptamine), with
the key enzymes of its synthesis being N-acetyltransferase (NAT)
and hydroxyindol-O-methyltransferase (HIOMT) [5].
The
discovery of MT stimulated researchers’ interest and for
a number of years the pineal gland was considered to be the
only source of MT.
The most important physiological actions of MT include control
of circadian and seasonal rhythms, stimulation of many metabolic
processes, inhibiting effect on pigment metabolism, anti-gonadotropic
effects, sedative and hallucinogenic action on the central nervous
system (CNS), and an inhibitory effect on cell proliferation
and division. MT stimulates oxygen consumption and production
of carbon dioxide, as well as glucose uptake by tissues, increases
concentration of ATP and creatine phosphate and contributes
to storage of glycogen in tissues [6,7].
The
intensity of MT metabolism depends on the level of... ...
Extrapineal
MT: where and why?
As
soon as highly sensitive techniques of analysis and identification
became available, MT and its catalytic enzymes began to be found
in extrapineal tissues, primarily those... ...
Gut
enterochromaffin cells are the main source of MT in organism
The
integrated application of methods of biological testing, thin-layer
chromatography and immunohistochemical analysis, enabled the
Russian scientists to be first to demonstrate the active MT
synthesis in human gut enterochromaffin cells (EC cells) [46].
Three parts were followed in MT identification for EC cells.
Initially it had to be found out whether ... ...
... ...
Melatonin regulates many gut functions
Besides,
the presence of MT in EC cells [46], receptors for MT and enzymes
involved in its synthesis from ... ...
... ...
General
conclusions
Summing up this review, it is necessary to reveal the main points
of data analyzed. The first, MT is an ubiquitously acting hormone
with a wide spectrum of effects. Among these are ... ...
The second, MT synthesis takes place not only ... ...
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