Irradiated mammals after nuclear accidents and experimental animals that received large doses of radiation show evidence of differences in brain serotonin levels, blood serotonin levels, tissue serotonin levels compared with radiation naïve mammals. Both short- and long-term radiation exposures affects the serotonin receptors that convert the chemical signal produced by serotonin into functional changes in the signal-receiving cell.

1. Dmitri Popov. PhD, Radiobiology. MD (Russia)
Advanced Medical Technology and Systems Inc.
Canada.

2.  Activation of serotonin receptors (5-HTR)
produces multiple effects on neurons.
Serotonin is an important brain
neurotransmitter and act as biological active
chemical to communicate information among
nerve cells.
Serotonin’s actions have been linked to
radiation’s effects on the brain and to
radiation toxicity.

3.  Irradiated mammals after nuclear accidents
and experimental animals that received large
doses of radiation show evidence of
differences in brain serotonin levels
compared with radiation naïve mammals.
Both short- and long-term radiation
exposures affects the serotonin receptors
that convert the chemical signal produced
by serotonin into functional changes in the
signal-receiving cell.

4.  5-hydroxytryptamine (5-HT; serotonin) is a neurotransmitter
essential for a large number of physiological processes including
the regulation of vascular and non-vascular smooth muscle
contraction, modulation of platelet aggregation, and the
regulation of appetite, mood, anxiety, wakefulness and
perception. To mediate this astonishing array of functions, no
fewer than 15 separate receptors have evolved, of which all but
two (5-HT(3A) and 5-HT(3B)) are G-protein coupled receptors.
This review will summarize our current understanding of the
structure and function of the G-protein coupled 5-HT receptors.
In particular, a systematic review of the available mutagenesis
studies of 5-HT receptors will be presented. This information will
be synthesized to provide a working model of agonist and
antagonist actions at a prototypic 5-HT receptor the 5-HT(2A)
receptor. Finally, examples will be given to demonstrate that a
detailed knowledge of the predicted structure of one receptor
can be useful for structure-based drug design. /Kroeze
WK1, Kristiansen K, Roth BL /

5.  Receptors Classification.
 2.1. Gq/11-Coupled Receptor Types
 2.1.1. The 5-HT2A Receptor
 2.1.2. The 5-HT2B Receptor
 2.1.3. The 5-HT2C Receptor.

6.  Gs-Coupled Receptor Types
 2.2.1. The 5-HT4 Receptor
 2.2.2. The 5-HT6 Receptor
 2.2.3. The 5-HT7 Receptor.

7.  Gi/o-Coupled Receptor Types
 2.3.1. The 5-HT1A Receptor
 2.3.2. The 5-HT1B Receptor
 2.3.3. The 5-HT1D Receptor
 2.3.4. The 5-HT1E Receptor
 2.3.5. The 5-HT1F Receptor
 2.3.6. The 5-HT5A (and 5-HT5B) Receptors 1
 3. The 5-HT3 Receptor, A Ligand-Gated Ion
 Channel

8.  Serotonin or 5-hydroxytryptamine (5-HT) is
a monoamine neurotransmitter.
Biochemically derived from tryptophan,
serotonin is primarily found in
the gastrointestinal tract (GI tract), platelets,
and the central nervous system (CNS) of
animals, including humans.
 Approximately 90% of the human body's total
serotonin is located in the enterochromaffin
cells in the GI tract, where it is used to
regulate intestinal movements.

9.  Severe nausea or vomiting associated with a
variety of diseases, radiation treatment, and
cancer chemotherapy, as well as postoperative
nausea and vomiting. Common treatments
include Compazine
(prochloperazime), Phenegram (prometazine)
 Other phenothiazines; haloperidol;
butyrophenone, droperidole, metoclopradide
(Reglan), all of which act by blocking dopamine
D-2 receptor, mediated stimulation of
chemoreceptor trigger zone and gastric motor
reflexes. /G.Rosenfeld/

10.  Serotonin acts on several classes of 5HT-
receptors. This receptors located in many
organs and tissues and located on cell
membranes.

11.  Wasps and hornets have serotonin in their
venom, as do scorpions.
 Stanley E. Manahan, Toxicological Chemistry
and Biochemistry, Third Edition. CRC Press,
2002. ISBN 9781420032123
 Michael R. Dobbs Clinical Neurotoxicology:
Syndromes, Substances, Environments, Expert
Consult. Elsevier Health Sciences, 2009. ISBN
9780323070997

12.  A. 5HT₁ - subtypes 5HT₁a - 5HT₁f. 5HT₁ receptors
are coupled to an inhibition in cAMP; stimulation
contracts arterial smooth muscle, especially in carotid
and cranial circulation. At pre-cynaptic sites,
neuronal serotonin release is inhibited. /G.
Rosenfeld/
 B. . 5HT₂ - subtypes 5HT₂a - 5HT₂c. 5HT₂ - receptors
are coupled to an increase in phospholipase C
activity. Stimulations of this receptors causes
contraction of vascular and intestinal smooth muscle
and increased microcirculation and vascular
permeability. Stimulation of this receptor on platelet
membranes causes platelet aggregatation; in the
CNS, this receptor mediates hallucinogenic effects.

13.  5HT₃ Receptors are coupled to an Na+, K+ ion
channel. Stimulation of this receptors in the area
postrema causes nausea and vomiting;
stimulation on peripheral sensory neurons causes
pain; /G. Rosenfeld/
 5HT₄ receptors increase cAMP; in the
gastrointestinal tract, these receptors mediate an
increase in secretion and peristalsis.
/G. Rosenfeld/
 5HT₅; 5HT₆; 5HT₇; These receptors are cloned
and their function under scientific investigation.
 /G. Rosenfeld/.

14.  Excessive levels of serotonin produce a
spectrum of specific symptoms
including cognitive, autonomic,
and somatic effects.
 http://en.wikipedia.org/wiki/Serotonin_syndr
ome

15.  Symptom onset is usually rapid, often occurring
within minutes of elevated serotonin levels. Serotonin
syndrome encompasses a wide range of clinical
findings. Mild symptoms may consist of increased
heart rate, shivering, sweating, dilated
pupils, myoclonus (intermittent tremor or twitching),
as well as overresponsive reflexes. However, many of
these symptoms may be side effects of the drug or
drug interaction causing excessive levels of
serotonin; not an effect of elevated serotonin itself.
Tremor is a common side effect of MDMA's action at
dopamine, whereas hyperreflexia is symptomatic of
exposure to 5-HT agonists.
 http://en.wikipedia.org/wiki/Serotonin_syndrome

16.  Moderate intoxication includes additional abnormalities
such as hyperactive bowel sounds, high blood
pressure and hyperthermia; a temperature as high as 40 °C
(104 °F) is common in moderate intoxication.
 The overactive reflexes andclonus in moderate cases may
be greater in the lower limbs than in the upper limbs.
Mental changes include hypervigilance or insomnia
and agitation.[1] Severe symptoms include severe increases
in heart rate and blood pressure that may lead to shock.
Temperature may rise to above 41.1 °C (106.0 °F) in life-
threatening cases. Other abnormalities include metabolic
acidosis, rhabdomyolysis, seizures, renal failure,
and disseminated intravascular coagulation; these effects
usually arising as a consequence of hyperthermia.

17.  The symptoms are often described as a clinical
triad of abnormalities:
 Cognitive effects: headache,
agitation, hypomania, mental
confusion, hallucinations, coma
 Autonomic
effects: shivering, sweating, hyperthermia, vasoc
onstriction, tachycardia, nausea, diarrhea.
 Somatic effects: myoclonus (muscle
twitching), hyperreflexia (manifested
by clonus), tremor.
 http://en.wikipedia.org/wiki/Serotonin_syndrom
e

18.  Under way.