H E A L T H A N D S T R E S S S T R E S S , N E U R OT R A N SM I T T E R S & THE "SECOND BRAIN" IN THE GUT
KEYWORDS: Vagusstoff, the "Big Three", the "Mighty Two", the "Dracula Hormone", Awakenings,Zyban, schizophrenia, Prozac, REM sleep, the dantian, Rabelais
purposeful during evolution. Thus, diarrhea
could have life saving value for an antelope
manifested by gastrointestinal complaints.
fleeing from a tiger since lightening the load
Numerous people get "butterflies" in the
performing before a large audience. Others
from the gut, where it was not immediately
are nervous or upset. A disgusting sight can
provide more strength in combat or a faster
might give you "agita" or a 'bellyache".
exit from a scene of potential peril. Hans
could be cited as well as disorders that are
stress consistently caused stomach ulcers in
(gastroesophageal reflux disease), peptic
ulcer, irritable bowel syndrome, ileitis and
ulcerative colitis. In some instances, these
observations explain other effects of stress
on the gut and how stress could contribute
reduce natural defenses or represent "fight
to some of the diseases listed. Over the past
few decades, research on neurotransmitters,
as well as an appreciation that the gastrointestinal tract has its own ALSO INCLUDED IN THIS ISSUE "brain" that operates independently of
• What And Where Are Neurotransmitters? the central nervous system, has provided
• What Do Neurotransmitters Do?
• An Odd Orchestra With No Conductor
• The Dopamine Dilemma
the brain are derived very early in life from
• The "Second Brain" In The Gut
the same primitive neural crest tissue. As
• Emotions And Energies From The Gut?
• Why We Know Relatively Little About Stress
the fetus develops, this tissue divides and
And Disease Or How Drugs Work
one section becomes the central nervoussystem and the rest migrates away to form a
September 2004 The Newsletter of THE AMERICAN INSTITUTE OF STRESS Page 2
separate nervous system for the gut. Later
Sunday was the most desperate day in mywhole scientific life. During the next night,
nervous systems. "Vagus" is derived from
however, I awoke again, at three o'clock,
Latin, where it means wandering, since the
and I remembered what it was. This time I
vagus winds from the brain stem through the
did not take any risk; I got up immediately,went to the laboratory, made the experimenton the frog's heart, described above, and atfive o'clock the chemical transmission of
and the gut, neurotransmitters also seem to
nervous impulse was conclusively proved."
hearts. Heart #1 was still connected to the
What & Where Are Neurotransmitters?
another at a junction between the two called
a synapse. They are particularly abundant in
stimulation of the vagus nerve attached to
acetylcholine allow neurons to talk to each
other in ways that affect how we feel, think
after a slight delay, heart #2 also slowed
and act. Most people are unaware that the
hypothesized that electrical stimulation of
the vagus nerve caused the release of some
Gershon notes in The Second Brain, a book
chemical into the fluid of chamber #1 that
flowed into chamber #2. He referred to this
substance as "Vagusstoff".
neurotransmitters line the length of the gut,
was acetylcholine and that it was released
following stimulation of the vagus and all
cells in the gastrointestinal tract than in the
entire remainder of the peripheral nervous
found that a substance closely related to
Henry Dale shared a 1936 Nobel Prize "for
to be discovered. Nearly every neurotransmitter involved in
transmission of nerve impulses." The two
communication in the brain in the head
had been close friends since 1902 when they
has been identified in the gut's "second brain". That should not be too surprising
identified acetylcholine in ergot extracts and
since both brains originated from the same
his analysis of its actions confirmed and
rudimentary tissue. The question is what are
greatly extended the application of Loewi's
many?The first neurotransmitter was What Do Neurotransmitters Do? discovered in 1921 by Otto Loewi, an
Austrian scientist during a dream that he
neurotransmitters have stimulating actions,
"In the night of Easter Saturday, 1921, 1
some have inhibiting effects and many, like
awoke, turned on the light, and jotted down
acetylcholine can do both, depending on the
a few notes on a tiny slip of paper. Then I
nature of the receptor. The two acetylcholine
fell asleep again. It occurred to me at sixo'clock in the morning that during the night Ihad written down something most important,
acting receptor is called nicotinic because it
but I was unable to decipher the scrawl. That
is specifically activated by the toxin found in
September 2004 The Newsletter of THE AMERICAN INSTITUTE OF STRESS Page 3
tobacco. The slow acting muscarinic receptor
is activated by muscarine found in poisonous
closely related chemically to noradrenaline
mushrooms. Acetylcholine will activate it but
was discovered in 1957. It was referred to as
the brain's "feel good" or "reward" chemical
by nicotine from tobacco or arecoline from
release was stimulated by nicotine, cocaine,
betel nuts (chewed by millions of people in
found that a dopamine deficiency in certain
satisfaction that often leads to addiction.
disease. As will be explained, dopamine may
nicotine receptors. It has been suggested that nicotine may be able to improve Alzheimer's patients since they have reduced acetylcholine nicotinic receptors in brain sites responsible for memory and learning. Scientists have long
suicide, obsessive-compulsive disorder and
acetylcholine and Alzheimer's since there is a
problems with anger control. Too little can
brains of patients in advanced stages.
common complaints in depression and other
stimulation of all skeletal muscles and some
morphine relieved pain, and heroin brought
because botulinus toxin blocks acetylcholine.
pleasure, by acting on receptors for some
chemicals with similar effects were isolated
affects specific muscles. Acetylcholine is also
and named endorphins, for "morphine from
present in sensory as well as motor neurons
within." In addition to reducing pain, they
and has even been found to play a role in
"runner's high" and promoted endurance by
by the Swedish physician and physiologist
demonstration that exercise, laughter, sex,
Ulf von Euler. He demonstrated that this was
touch, and massage can increase endorphin
production helps to explain many anecdotal
observations and why such activities tend to
the key neurotransmitter in the sympathetic
have varied effects. Beta-endorphins activate
natural killer cells that boost immune system
stress and causes an increase in heart rate
resistance to infections and cancer. An Odd Orchestra With No Conductor
be essential in retrieving certain types of
memories. Researchers are now studying its
important members of the neurotransmitter
norepinephrine are often referred to as "The
characterized by difficulties and disturbances
Big Three". All these neurotransmitters are
1970 Nobel Prize for "discoveries concerning
and forth to one another. Others that are
also involved in the response to stress are
September 2004 The Newsletter of THE AMERICAN INSTITUTE OF STRESS Page 4
acid), which some view as illustrating the yin
hormone that is manufactured in the pineal
and yang balance of neurotransmitters. Both
gland at the base of the brain. It is called
are present in nearly all synaptic connections
"The Dracula Hormone" because it is
secreted at night and regulates sleep-wake
cycles. Serotonin in the pineal is converted
inhibitory role. It's not quite that simple
reversed every 24 hours. This sequence of
receptors, one of which, NMDA, controls the
events takes exactly 25 hours when subjects
flow of calcium into nerve cells. Drugs that
are placed in a cave at constant levels of
act as NMDA antagonists have been found to
decrease depression and improve memory.
impaired and increased calcium influx can
automatically reset the body’s clock to a 24
hour day. Melatonin makes you feel sleepy
at night and the surge of stress hormones in
neurotransmitter in the brain and blocks the
the early morning is what wakes you up.
Melatonin is also a powerful antioxidant that
anxiety. Tranquilizers like Valium as well as
blocks the free radical damage thought to
barbiturates and alcohol all act by facilitating
play a role in age related diseases such as
GABA activities. Depressed individuals have
cancer, cataracts, coronary, Alzheimer's and
glucagon, and cholecystokinin that control
depressed patients that may have diagnostic
digestion, hormones (vasopressin, oxytocin,
prolactin, thyrotropin, and gonadotropin and
doubled. Antidepressants like Prozac that are
have widespread and varied effects. Soluble
thought to act by boosting serotonin also
gases like carbon monoxide and nitric oxide
are recent additions. Nitric oxide reduces
inflammation, relaxes smooth muscle in the
two different types of amino acids, speeds
gut to promote peristalsis and in coronaries
to relieve angina, stimulates the release of
increases inflammatory reactions during the
neurotransmitter orchestra are constantly
anxiety and depression and one was recently
approved for treating chemotherapy induced
(corticotropin releasing factor) also known as
The Dopamine Dilemma
(CRH) is a much larger peptide composed of
chemical messengers does from this tangled
41 amino acids. During stress, it is secreted
interrelationships is impossible, as illustrated
hypothalamic-pituitary-adrenal response that
by the very versatile dopamine. So much
causes ACTH to stimulate the production of
has been written about the role of
cortisol. In addition, it activates sympathetic
dopamine in sex, love, compulsive
and behavioral responses to stressors and
gambling, smoking, drinking, and other
causes the release of GABA in the amygdala,
addictions that provide pleasure, that a
a portion of the brain that is often referred
movie was devoted to it. The prize
September 2004 The Newsletter of THE AMERICAN INSTITUTE OF STRESS Page 5
winning Dopamine, which premiered at the
whether all of the above are merely different
effective in treating addictions. Zyban, a
manifestations of dopamine activities and if
sustained release version, is used to aid
mechanisms because you don't learn as well
contradictory effects, including: promoting
if you're not rewarded. Zyban works best in
feelings of rage or falling in love, making
patients who are not motivated as opposed
depressed, schizophrenic, decreasing blood
other addictive drugs increase dopamine by
binding to sites that remove it but as these
similar fashion are also associated with an
increased incidence of compulsive gambling,
three scientists who showed that dopamine
that the high rate of drug use and
Parkinson's disease was due to a deficiency
smoking in people with eating disorders
of dopamine in a certain portion of the brain. could be partly explained by their
This led to the discovery of L-dopa, which is
increased need for dopamine. In one
study, obese individuals had less dopamine
receptors than controls of normal weight and
model of severe Parkinson's, rabbits that had
the heavier the individual, the fewer the
been in a sustained stupor awakened rapidly
This was the basis for Awakenings, a
and a shortage here is associated with poor
disease was seen following the Spanish flu
pandemic after World War I that killed up to
40 million people and caused encephalitis
personality given to bouts of paranoia or
that left many others in a permanent coma.
In the movie, Robin Williams, a neurologist
assigned to a ward of such patients, decided
effects. Risperdal, one of the most popular,
breasts in young males, in addition to the
that he is no longer a teen-ager and how he
and other treated patients try to cope with
dizziness, nausea, weight gain, constipation,
the brain can cause depression, which is alsocommon in Parkinson's. While most attention
The “Second Brain” In The Gut
noradrenaline are also effective. Since these
important influences on the gastrointestinal
determine which is being affected. Drugs like
tract. Antidepressant and other drugs that
affect neurotransmitter levels are frequently
noradrenaline and Wellbutrin raises levels of
all three but particularly dopamine.
nausea, diarrhea, or constipation. This is not
September 2004 The Newsletter of THE AMERICAN INSTITUTE OF STRESS Page 6
danger signal from above, it also helps to
messengers in the brain are also found in
abundance in the nerve supply to the gut.
immune system responses. Mast cells in the
lining of the small intestine and colon release
communicates with the brain via the vagus,
it has a mind of its own. It regulates the
response to attract immune cells from the
colon by mixing food with digestive enzymes
blood stream into the affected area to deal
and pushing it along via peristalsis. It is
with animal bites, knives or other foreign
structurally quite similar to the central
objects that might allow infectious material
messages are also constantly being sent up
the line. The enteric nervous system signals
the brain if it senses dangerous or infected
provides "second-to-second control" and
abdominal pain or diarrhea. Just like the primary brain, the "second brain" in the gut is able to learn, remember, and also produce emotion-based feelings. The
nervous system are entirely contained in the
sensation of fulfillment, satisfaction and
gut, it can be disconnected from the spinal
cord and brain to study various parts as they
turkey, which is converted into serotonin or
opportunity to study the effects of different
neurotransmitters. For example, serotonin
carbohydrates that not only increases levels
plays an important role in peristalsis by
of tryptophan in the brain but pulls blood
constriction and relaxation are cordoned up
benzodiazepines that alleviate pain and are
and down the line. Altering serotonin levels
found in anti-anxiety drugs like Valium.
synthesizes benzodiazepines from chemicals
why half of senior citizens in nursing homes
in our foods, bacterial actions, or both, we
suffer from fecal incontinence, diarrhea and
do know that during severe stress, the gut
benzodiazepines to the brain to reduce pain
and anxiety. Some believe that the brain in
the gut provides a major source of relief
serotonin. By placing an artificial pellet in the
brain, the "second brain" has receptors for
intestine, it is also possible to study the
opiates. Drugs like morphine and heroin also
influence of different drugs on motility and
attach to the gut's opiate receptors and both
brains can become addicted to opiates. Emotions And Energies From The Gut?
head to the enteric nervous system. Thus,
interconnected that both have natural 90-
minute "sleep cycles." In the brain, slow-
for "fight or flight". This response can vary
wave sleep is interrupted by periods of rapid
from slowing down normal intestinal motility,
shutting it down completely or evacuating
September 2004 The Newsletter of THE AMERICAN INSTITUTE OF STRESS Page 7
interrupted by similar short bursts of rapid
often rub to obtain good luck. In the King
James Version of the Bible's Song ofSolomon, "bowels" are "the seat of the
nightmares after a late night spicy snack and
others develop cramps, agita or diarrhea
Testament also translate "bowels" as "the
when they are very nervous or angry.
deep, inner seat of tender emotions in the
whole personality". Expressions like "My gut
reaction is", "he has a lot of guts" and "I
can't stomach that fellow" still support the
sleep. In some instances, antidepressants
notion that feelings can originate in various
can make all these complaints disappear and
in others, there may be an improvement in
The use of "gut" to denote spirit or
force of character, usually considered as
being brain attributes, is a slang word that
be so unpredictable. Depression is associated
first appeared in the 1890's. Having "guts"
with poor appetite, decreased salivation and
constipation. On the other hand, Prozac and
endurance and variations of these such as
antidepressants that increase brain serotonin
constipation. In one study, when a traceable
intestinal fortitude. In addition to feelings,
pellet was put in the "mouth end" of isolated
the gut is also believed to be an important
guinea pig colon, it traveled down to the
"anal" end just as it would inside the animal.
500 years ago, "From the gut comes the strut, and where hunger reigns,
the pellet passed through twice as fast but
strength abstains." In the martial arts, Qi
is believed to be stored in the dantian to
produce the "elixir of immortality." This
ancient Chinese term refers to a "center of
energy" located deep in the abdomen at the
constipation, larger doses cause constipation
level of the solar plexus, a large network of
and some people get diarrhea. In addition,
nerves behind the stomach. A karate chop or
Prozac stimulates sensory nerves resulting in
boxing blow that affects the solar plexus can
nausea or even vomiting. While these drugs
incapacitate an opponent by causing severe
pain and "knocking the wind out" due to
serotonin, less is available for the gut, where
else in the body to regulate peristalsis and
The cerebral and gut brain
during stress is a mystery. In addition to
connection is so close that determining
serotonin, there are 'brain-gut" receptors for
which is doing what can be difficult and
numerous other neurotransmitters with wide
confusing. This is especially true when it
ranging functions. Why these are present in
comes to responses to stress as well as
both brains is not clear, but suggests that
numerous drugs that increasingly appear to affect both brains.
the heart rather than the brain was the seat
of emotions but in other cultures it was the
Why We Know Relative Little About
gut. Indian deities are often depicted with
Stress And Disease Or How Drugs Work prana energy to sustain life was stored.
and articles about the response to stress and
Chinese statues of Hotei, the obese, "Happy
Cannon's "fight or flight" sympathetic
September 2004 The Newsletter of THE AMERICAN INSTITUTE OF STRESS Page 8
r e s p o n s e s a n d S e l y e ' s " A l a r m R e a c t i o n "
r e l a t e d d i s o r d e r s . F e w w o u l d b e w i l l i n g
a n d " G e n e r a l A d a p t a t i o n S y n d r o m e "
t o m a k e t h e s u b s t a n t i a l i n v e s t m e n t
f e a t u r i n g t h e r o l e o f t h e p i t u i t a r y -
n e e d e d t o p r o v e b o t h t h e e f f i c a c y a n d
a d r e n a l - c o r t i c a l a x i s i n t h e p r o d u c t i o n o f
s a f e t y r e q u i r e d t o o b t a i n F D A a p p r o v a l .
c o r t i s o l a n d c o r t i c a l h o r m o n e s . M o r e
A n o t h e r s t u m b l i n g b l o c k i s t h a t e v e n i f
r e c e n t r e s e a r c h h a s f o c u s e d o n h o w
y o u d e m o n s t r a t e t h a t a n e w d r u g
p r o v i d e s b e n e f i t s a n d i s a s s o c i a t e d w i t h
r e s i s t a n c e t o i n f e c t i o n s a n d p o s s i b l y
a c o n s i s t e n t e f f e c t o n s o m e s p e c i f i c
c a n c e r a n d c a u s e s s h o r t t e r m m e m o r y
n e u r o t r a n s m i t t e r , t h e r e i s n o p r o o f t h a t
l o s s a n d c o g n i t i v e d i s t u r b a n c e s , a n d h o w
t h i s i s t h e m e c h a n i s m o f a c t i o n
r e s p o n s i b l e . W e a r e j u s t b e g i n n i n g t o
h o r m o n e s c a n c o n t r i b u t e t o d e p r e s s i o n ,
a p p r e c i a t e t h i s w i t h r e s p e c t t o P r o z a c
a n x i e t y , P T S D a n d o t h e r p s y c h i a t r i c
p r o b l e m s . T h e r e i s r a r e l y a n y r e f e r e n c e
p r e s u m a b l y w o r k b y b o o s t i n g s e r o t o n i n
t o , m u c h l e s s d i s c u s s i o n , o f e f f e c t s o n
b u t h a v e b e e n f o u n d t o a f f e c t o t h e r
n e u r o t r a n s m i t t e r s t h a t m o s t l i k e l y a l s o
m e d i a t e d e p r e s s i o n , a v a r i e t y o f a n x i e t y
p l a y a r o l e . S i m i l a r l y , i t i s n o w q u i t e
d i s o r d e r s , a n d a d d i c t i v e b e h a v i o r s t h a t
o b v i o u s t h a t t h e b e n e f i t s o f s t a t i n s a r e
n o t r e l a t e d t o l i p i d l o w e r i n g b u t r a t h e r
u n d e r s t a n d a b l e . S u c h r e s e a r c h i s i n i t s
t o r e d u c i n g i n f l a m m a t i o n a n d o t h e r
i n f a n c y f o r s e v e r a l r e a s o n s . D e t e r m i n i n g
" p l e i o t r o p i c " a c t i o n s .
t h e c o n c e n t r a t i o n s o f c a t e c h o l a m i n e s ,
A s i n d i c a t e d p r e v i o u s l y , t h e s p a c e
c o r t i s o l o r o t h e r b a r o m e t e r s o f s t r e s s i n
c o n s t r a i n t s a n d t h e f o r m a t o f t h i s a n d
b l o o d , c e r e b r o s p i n a l f l u i d , o r s a l i v a a r e
m o s t N e w s l e t t e r s m a k e i t i m p o s s i b l e t o
n o w s t a n d a r d , a n d a c c u r a t e , r e p r o d u c i b l e
i n c l u d e i m p o r t a n t r e l e v a n t m a t e r i a l a n d
p r o c e d u r e s t h a t a r e r e l a t i v e l y i n e x p e n s i v e
r e f e r e n c e s t h a t m a n y r e a d e r s h a v e
a n d o f t e n r e i m b u r s a b l e a r e a v a i l a b l e .
r e p e a t e d l y r e q u e s t e d . B e c a u s e o f t h i s
a n d r i s i n g p r o d u c t i o n a n d p o s t a g e c o s t s ,
n e c e s s a r i l y r e f l e c t w h a t i s g o i n g o n i n
w e a r e c h a n g i n g o v e r t o a n e l e c t r o n i c
t h e b r a i n . M e a s u r i n g l e v e l s o f s p e c i f i c
v e r s i o n t h a t w i l l a l l o w a d d i t i o n a l a n d
b r a i n n e u r o t r a n s m i t t e r s i s v e r y c o s t l y ;
f r e q u e n t l y m o r e c u r r e n t c o v e r a g e o f
t e c h n i q u e s v a r y a n d r e q u i r e s p e c i f i c
c e r t a i n t o p i c s . T h i s s h o u l d a l s o p r o v i d e a
s o p h i s t i c a t e d e q u i p m e n t a n d e x p e r t i s e .
m o r e c o n v e n i e n t w a y t o s a v e a n d
T h i s m a k e s i t d i f f i c u l t f o r o t h e r s t o
r e f e r e n c e i s s u e s t h a t a r e o f p a r t i c u l a r
c o n f i r m r e s u l t s o r t o c o n d u c t d o u b l e
t h e r e f o r e
b l i n d s t u d i e s t h a t s a t i s f y t h e s c i e n t i f i c
n e c e s s a r y f o r s u b s c r i b e r s t o s e n d
c o m m u n i t y ' s r e q u i r e m e n t s f o r p r o o f .
t h e i r p r e f e r r e d e - m a i l a d d r e s s t o :
M o s t s u c h r e s e a r c h i s s p o n s o r e d b y
s t r e s s 1 2 5 @ o p t o n l i n e . n e t
p h a r m a c e u t i c a l c o m p a n i e s e a g e r t o
a s s o o n a s p o s s i b l e t o i n s u r e
d e v e l o p b l o c k b u s t e r d r u g s f o r s t r e s s
u n i n t e r r u p t e d s e r v i c e .
Copyright2004 by the American Institute of Stress. All rights reserved. Health and Stress ISSN # 1089-148X 124 Park Avenue Yonkers, NY 10703 ANNUAL SUBSCRIPTION RATES:
The Masoretic Accent System The Tiberian Masoretes invented a complicated system of accent marks to accompany the biblical text. While it is not necessary for most Hebrew students to learn all of the intricacies of the system, there are a few points which can be of immense help in reading and interpreting the Hebrew text. The Masoretes actually made two systems of accents, one for so called
Is a once-daily human GLP-1 (Glucagon-Like Peptide-1) analogue approved for the treatment of type 2 diabetes in adults.1 Has 97% similar to the body’s own hormone (GLP-1). GLP-1 is a natural hormone in the body that plays a critical role in maintaining a healthy level of sugar in the blood. In type 2 diabetes, GLP-1 production and Lowers blood sugar levels by stimulating the