THE CONCEPT OF NEUROHUMORAL TRANSMISSION IN

AUTONOMIC NERVOUS SYSTEM PHARMACOLOGY

A Ph.D RESEARCH SEMINAR

PRESENTED BY

TOLOGBONSE, ADEDAYO ADEDOYIN

13/PG/PH/PT/PH.D/002
DEPARTMENT OF PHARMACOLOGY AND TOXICOLOGY
UNIVERSITY OF UYO, UYO

SUPERVISORS: (1) PROF. P. UNEKWE

(2) DR. H. O. C. MBAGWU

OCTOBER, 2016
 ABSTRACT
This research seminar give a detailed comprehensive retrospective
review of the concept of neurohumoral transmission in autonomic
nervous system.The concept of chemical substance mediating nervous
activity at the autonomic nervous system is now classically reffered
to as neurohumoral transmission and was originally put forward by
Du-Bois Raymond in 1877.The vesicles of both cholinergic and
adrenergic nerves contain primary transmitters, namely; acetylcholine
and noradrenaline respectively; they also contain other substances in
addition to the primary transmitters. They also participate in feedback
inhibition of the same and nearby nerve terminals.Otto Loewi (1921)
provided the first proof of the chemical mediation of synaptic
transmission with his studies on the frog heart and its vagal
innervation in vitro. In 1926 Loewi and Navratil provided evidence
that "vagusstuff" was actually acetylcholine. Hence, Otto Loewi may
aptly be reffered to as the pioneer of the concept of modern
neurohumoral transmission.Neurohumoral transmission is a dynamic
process that involve the Passage of electrical current along an axon in
the form of an action potential , with a resultant depolarization of
nerve terminals and the release (by exocytosis) of chemical substances
called neurotransmitters into the synaptic. Neurotransmitters released
into the cleft diffuse to and interact with receptors on postsynaptic
neurons or effector cells to produce tissue excitation or inhibition.
 ABBREVIATIONS

Ach Acetylcholine

ANS Autonomic nervous system

ChAT Choline Acetyl transferase

CHT Choline transporter

CGRP Calcitonin Gene Related Peptide

COMT Catechol –O- Methyltransferase

DOPEG 3,4-dihydroxy Phenylethylene glycol

DOPGAL 3,4-dihydroxy phenyl glycoaldehyde

DOMA Dihydroxy Mandelic acid

EPSP Excitatory postsynaptic(junctional)potential

GABA Gamma amino Butyric Acid

GPCRS G Protein coupled receptors

IPSP Inhibitory postsynaptic(junctional)potential

MAO Mono amine Oxidase

MOPEG 3-Methoxy-4-hydroxyphenyl ethylene glycol

M 1-5 Muscarinic Receptor 1-5

NE Norepinephrine

NM NicotinicNeuromuscular receptor

NPY Neuropeptide Y

VIP Vasoactive intestinal Polypeptide

VMA 3-Metyl,4-Hydroxy Mandelic Acid

 TABLE OF CONTENT

page

ABSTRACT I

ABBREVIATIONS II

TABLE OF CONTENTS III

INTRODUCTION ;

The concept of Neurohumoral transmission 1

History of f Neurohumoral transmission 1-2

Neurotransmitter of the ANS 2-4

Receptors of the ANS 5-8

LITERATURE REVIEW;

Defination of Neurohumoral transmission theory 6-7

Criteria for a neurotransmitter 8-9

Steps in neurohumoral transmission 9-12

Types of neurohumoral transmission 13-14

METHODOLOGY/APPLICATION;

Example of application of cholinergic system 15-19

Example of application of aldrenergic system 20-25

RESULT/EFFECTS/CONCLUSION/RECOMMENDATION 26-27
 INTRODUCTION

The origin of the concept of Neurohumoral transmission.

It is difficult to say who originated the theory of neurohumoral
transmission, especially on the priority complex which seems to
tortures many minds (Fondo,1952).
According to Fondo 2016, the concept of role of hormones in
the organism is a very old one ; many investigation between
Hippocrates epoch research and our glorious twentieth century may
have thought of a possible intervention in humoral agents in nervous
activity, but they probably have found that their experimental data
were neither strong enough nor convincing enough to serve as the
basis for a new hypothesis.
Akah, 2013 reported that the concept of chemical substances
mediating nervous activity at the autonomic nervous system ,where
there is established gaps/cleft was put forward by Du-Bois Raymond
in 1877.This concept was supported when Schmiedeberg and Keffe
noticed the similarity between the effects of muscarine and electrical
stimulation of the vagus nerve, and the antagonism by atropine of the
two effects. The history of neurohumoral transmission in the
autonomic nervous system
 A. Lewandowsky (1898) and Langley (1901) independently
noted the similarity between the effects of injection of extracts of the
adrenal gland and stimulation of sympathetic nerves.
B. Elliott (1905) postulated that the sympathetic nerves release
minute amounts of an epinephrine-like substance.
C. Cannon and collaborators (1921) showed actual release of a
epinephrine like compound upon stimulation of a sympathetic nerve.
D. von Euler (1946) showed that the substance released was
actually nor-epinephrine.
E. Langley (1905) suggested that effector cells have excitatory
and inhibitory "receptive substances", and that the response to
epinephrine depended upon which type of substance was present.
F. Dixon (1907) was so impressed by the similarity between the
effects of muscarine and the effects of stimulating the vagus nerve
that he proposed that the vagus released a muscarine-like substance.
G. Otto Loewi (1921) provided the first proof of the chemical
mediation of synaptic transmission with his studies on the frog heart
and its vagal innervation in vitro. In 1926 Loewi and Navratil
provided evidence that "vagusstuff" was actually acetylcholine.
- Neurotransmitters of the ANS
 Almost All sympathetic postganglionic neurons release NE.
a. The sympathetic postganglionic innervation of the sweat glands is
an exception to this rule, since it releases ACh.
 . All other parasympathetic efferent neurons release ACh
 The vast majority of neurons which have been examined in
both the ANS and CNS appear to contain more than one
neurotransmitter. Almost all sympathetic postganglionic neurons
innervating the vasculature of the gut and hind limbs for example
contain NE and neuropeptide Y (NPY). On the other hand, the
sympathetic postganglionic neurons innervating the sweat glands
release ACh (not the expected NE), and also contain at least two other
peptides, ie Calcitonin Gene Related Polypeptide (CGRP), and
Vasoactive Intestinal Polypeptide (VIP). Many postganglionic
parasympathetic neurons contain ACh and VIP.(Kenjevic,1974).
- The amount of release of these peptides which are co-localized with
classical neurotransmitters appears to be dependent upon the rate of
firing of the neuron. In sympathetic nerve terminals innervating
vascular smooth muscle, for example, cerebral, coronary, renal,
skeletal muscles) mild degrees of stimulation or reflex activation
cause the release of NE alone. This results in a brief period of
vasoconstriction. On the other hand, intense stimulation of these
nerves or a profound stress (intense reflex) causes the release of both
NE and NPY, and leads to a prolonged period of vasoconstriction. In
the presence of alpha 1 antagonists, the brief vasoconstrictor effects of
NE are blocked, but intense stimulation still causes prolonged
vasoconstriction which is NPY-induced. This latter effect can be
blocked by the addition of an NPY receptor antagonist. Effcts of NPY
include direct postjunctional contractile effects, potentiation of the
contractile effects of the other sympathetic cotransmitters, and
inhibitory modulation of stimulation-induced release of all the
sympathetic cotransmitters. In the ANS, the principal postsynaptic
NPY receptor is a Y1 subtype. Y2 receptors mediate the presynaptic
effects of NPY both in the periphery and in the CNS. The
development of NPY receptor antagonists has recently undergone a
considerable breakthrough, (Because NPY profoundly stimulates
feeding) and you will doubtless be seeing such drugs in the future.
Considerable evidence is being accumulated which suggests that ATP
is a third sympathetic co-transmitter.

4. Visceral Afferents associated with the sympathetic nervous

system are located in the dorsal root ganglia. Tlhese ganglia are
arranged segmentally, and project to both sympathetic ganglia
and peripheral targets such as the heart. Many visceral afferents
probably release substance P or glutamate, however numerous
neuropeptides including angiotensin, bombesin, CGRP, VIP,
enkephalin, oxytocin, and somatostatin have been identified in
the perikarya of dorsal root ganglion afferents.
Visceral afferents associated with the parasympathetic nervous
system are found most commonly in the nodose ganglia and
travel widely through the body via branches of the vagus nerve.
They have also been found in the sacral dorsal root ganglia.
 They also have been shown to contain a wide varierty of
neuropeptides.
Receptors of the ANS
 All autonomic preganglionic neurons primarily activate
nicotinic receptors (Nn).
a. A somewhat different nicotinic receptor is also found at
the skeletal neuromuscular junction (Nm).
b. Molecular cloning studies have indicated the presence of
atleast a dozen subtypes of Nicotinic receptor, especially
in the CNS. Nicotinic receptors are ligand gated ion
channels whose activation causes a rapid increase in
cellular permeability to Na or Ca, depolarization, and
excitation. More in the future.
 . Postganglionic parasympathetic neurons activate muscarinic
receptors. Molecular cloning studies have indicated the
presence of at least 5 subtypes of Muscarinic receptor. M2
receptors predominate in the heart where they mediate
parasympathomimetic effects. Muscarinic receptors are G
protein coupled receptors (GPCRs). Responses to muscarinic
receptors are slower than to nicotinic reeptors, and can be
either excitatory or inhibitory. The responses are also not
necessarily linked to changes in ion permeability. M1
receptors are found in autonomic ganglia (even though the
major effect of ACh in ganglia is through Nicotinic (Nn)
 receptors), and some secretory glands. M2 Receptors
predominate in the heart. M3 and M2 receptors are found on
many smooth muscles and glands. The M3 receptor
predominates in the bladder. M3 receptors mediate erection of
the penis. Most other organs contain both M2 & M3. More in
the future.All (M1-M5) are found in the CNS.
(Rang,2007;Ehlert,2003).M1 receptors also occur at the gastric
parietal cells where their stimulation leads to gastric
secretion,they also occur at autonomic ganglia.The M2
receptors are found in the heart,hence called cardiac
muscarinic receptors.(Akah,2013).
 Postganglionic sympathetic neurons activate adrenergic
receptors(α1- adrenergic receptors).There are at least 6
subtypes of alpha receptor, and three beta receptors. All
adrenergic receptors are G protein coupled receptors which
influence the generation of second messengers and/or ion
channels,otherwise called α1-postganglionic or postsynaptic or
postjunctional adrenergic receptors.
 Presynaptic Receptors(α2-preganglionic or presynaptic or
prejunctional adrenergic receptor).
 Heteroreceptors vs autoreceptors:
 1. Heteroreceptors are presynaptic receptors found
on a neuron that respond to neurotransmitters,
neuromodulators, or neurohormones released from a different
 cell. Autoreceptors respond to neurochemicals released from
the same neuron being evaluated.
 a. The best characterized presynaptic receptor, the alpha 2
receptor, is found on sympathetic postganglionic adrenergic
nerve terminals (as well as other sites). Activation of this
receptor results in the inhibition of the release of NE-
otherwise called presynaptic inhibition of NE).
 The alpha 2-a autoreceptor is most potent in blocking NE
release. Alpha 2 autoreceptors also inhibit the release of NPY
from sympathetic postganglionic nerve terminals. Beta 2
autoreceptors are also found on noradrenergic nerve terminals,
and the activation of these Beta 2 receptors facilitates the
release of NE and NPY. Autoreceptors are also found in the
parasympathetic nervous system where M2 & M4 presynaptic
receptors respond to released ACh by an inhibition of the
release of ACh. Presynaptic nicotinic autoreceptors facilitate
the release of ACh.

 b. Alpha 2 (a and c) receptors are also found on

parasympathetic terminals and therefore catecholamines can
inhibit the release of ACh via a presynaptic heteroreceptors.
Similarly M2 and M4 cholinergic heteroreceptors mediate the
inhibition of NE release from sympathetic postganglionic
nerve terminals by closely adjacent parasympathetic nerve
terminals. Thus, for example, in the SA node of the heart the
 opposing effects of Acetylcholine and Norepinephrine on
cardiac rate (at the SA node) are mediated not only by the
opposite effects of the two neurotransmitters on pacemaker
cardiac cells, but also by their mutual inhibition of the release
of the opposing neurotransmitter by actions of heteroreceptors
on sympathetic or parasympathetic nerve terminals.

 Nicotinic heteroreceptors on sympathetic nerve terminals

facilitate the release of NE. NPY heteroreceptors also inhibit
the release of NE, ACh, GABA, Glutamate, Serotonin, CGRP,
and Substance P. Heteroreceptors respond to many different
neurotransmitters, including GABA, glutamate, adenosine,
prostaglandins, histamine, enkephalins etc also modify the
neurally mediated release of various neurotransmitters.
(Millar,2003).
 Fig 1a showing the
diagrammatic presentation of the receptor and transmitter
location in the autonomic nervous system (Akah, 2013).
Definition of Neurohumoral transmission theory.
Neurohumoral transmission theory is essentially based on the
view that neuronal areas are living tissues; thus the chemical
transformations, heat production and electrical activity is seen on
stimulation of nerve.
The classic work of Langley shows that the ganglia of the automomic
nervous system and the junctions of postganglionic fibers and effector
organs shows a definite sensitivity to chemical agents such as nicotine
and epinephrine. The autonomic nervous system (ANS) is the system
that maintains homeostasis by modulating the activity of smooth
muscle, cardiac muscle, and glands. Activity of the ANS is regulated
on a reflex basis and modulated by the central nervous system (CNS).
Events involved in impulse transmission in the ANS.
- Two neurons are required for transmission in the ANS.
1. Preganglionic neuron – cell body lies in the SNC, and the
axon passes into the periphery.
2. Postganglionic neuron – cell arises from a group of nerve cell
bodies in the periphery (called a ganglion), and the axon
travels to an effector organ.

Two events are required to pass an impulse through this system.

1. Passage of electrical current along an axon in the form of an
action potential.
2. Resultant depolarization of nerve terminals and the release
(by exocytosis) of chemical substances called
neurotransmitters into the synaptic (or junctional) cleft.
- Terminal axons of preganglionic and postganglionic neurons have
numerous varicosities (“swollen” areas) often visualized as “nerve
terminals” which contain neurotransmitters in vesicles .- The synaptic
or junctional cleft ; the gap between a nerve terminal and a nerve cell
body or between a nerve terminal and an effector cell, respectively.
-Neurotransmitters released into the cleft diffuse to and interact with
receptors on postsynaptic neurons or effector cells to produce tissue
excitation or inhibition.Release of NA occur by exocytosis.This
process is called neurohumoral transmission.
Criteria required for a substance to be a neurotransmitter
According to Koelle 1962 and Akah 2013; this was also supported by
Unekwe, (2015). A neurotransmitter should possess the following
features:
-It should be present in the presynaptic and postsynaptic nerve
endings.
-It should be released following the nerve stimulation,
-Its application produces responses similar to those produced by the
nerve stimulation,
-There should be body mechanism (enzymes) to metabolize the
substance at the site ofsynthesis which is the nerve ending.
-There should be drugs that can modify ( antagonize or potentiate) the
responses produced by both nerve stimulation and the proposed
neurotrasmitter substance.
Steps in neurohumoral transmission
The steps are in a systematic order,and include:
-Impulse conduction
-Transmitter release
-Action on the postsynaptic membrane
-Postjunctional activity and
-Termination of transmitter action.(Koelle,1962).
Fig. 1.b: Impulse Transmission/ conduction in a typical
Neurohumoral synaptic junction
Fig 2: Site of Autonomic Synaptic and Non-synaptic
Transmission at neuroeffector junctions.Adapted from
Burnstock,(2008).
Types of neurohumoral transmission
There are two main classes of neurohumoral transmission,namely;
1.Cholinergic transmission system –It is believed to prepare the body
for a quite and smooth living;it is concerned with conservation of
energy.(Akah,2013);here the chief transmitter is Acetylcholine(ACH),
-In Cholinergic transmission, acetylcholine is synthesised in
cholinergic nerve junction in a series of reactions catalysed by the
enzyme Choline acetyltrasferase (ChAT),after the transport of
choline into the presynaptic nerve terminal by a sodium-dependent
choline trasporter VB (CHT) as shown in the sketch Fig.2b below.

Fig. 2b showing Generalized cholinergic junction

Example of applications of cholinergic mechanism;
1. Neurochemistry - Cholinergic Mechanisms of Learning and
Cognition

Fig 3: Effect of an ACh injection into primary visual cortex of an

anesthetized monkey.(Rauch,2008).

On the right side the voxel distributions of affected (red) and

not affected (green) voxels are depicted with their corresponding time
courses. On the lower right the dynamics of ACh and its metabolite
choline (Ch) are shown.
The brain is the most complex organ of our body. It enables us
to do complex behavioral tasks and find ready-to-go solutions for
abstract problems. The brain uses many different subsystems to
respond in an adequate manner to a stimulus from the environment.
One of these systems is the cholinergic network located in the basal
forebrain and extending from there through the entire cortex. Learning
and cognition heavily depend on an intact cholinergic system, which
guarantees attention to important and relevant cues from the outside
world and also insures subsequent memory formation of these cues to
create an integrated and reliable experience for adequate behavior in
later life.
The importance of the cholinergic system becomes dramatically
evident in the devastating effects of progressive Alzheimer disease..
The extracellular space is an integrated functional part of information
processing in the brain. The release of chemical substances into the
extracellular space for signaling provides an interesting opportunity
for monitoring signal transduction in the living brain. This study is
useful in monitoring the cholinergic effect on the dynamics of the
neurotransmitters glutamate and GABA and of the neuromodulators
serotonin and dopamine. Metabolites such as lactate which are linked
to the neurovascular coupling process.
2. Study of the pathophysiology of sleep in affective Disease. May
require a comprehensive approach, i.e., one using integrative
models.Here several central neurotransmitter abnormalities may be
contributory. For instance, serotonergic and noradrenergic
mechanisms are involved in sleep physiology, and interaction between
neurotransmitter systems may be causal.(Rauch, 2008).
3.Adrenergic transmission –This transmission involves the
activation of the sympathetic nervous system which evokes diffuse
responses,mainly concerned with the expenditure of energy. Nor-
aldrenaline (NA) is the main transmitter; other transmitter include
aldrenaline(epinephrine);NA is synthesised in the noradrenergic
junction; the rate limiting step in the biosynthesis of noradrenaline is
the conversion of tyrosine to dopa by tyrosine hydroxylase.See details
in Figure 5.
Also,a major factor controlling the synthesis of epinephrine in the
adrenal medulla is the level of glucocorticoids.
Fig 4: Effect of Adrenergic Stimulation in body System
Fig.5: Schematic diagram of a generalised noradrenergic junction in
biosynthesis of noraldrenaline.
Fig 5.2 Storage of Noraldrenaline after synthesis
 The rate limiting step in the biosynthesis of
catecholamines is the conversion of tyrosine to dopa by
tyrosine hydroxylase. Another major factor controlling
the synthesis of epinephrine in the adrenal medulla is the
level of glucocorticoids secreted by the adrenal cortex.
The intra-adrenal portal vascular system carries
corticosteroids directly to adrenal medullary chromaffin
cells where they induce the synthesis of PNMT. The
activity of TH and DBH are also enhanced by
corticosteroids. Thus any stress which evokes enhanced
secretion of adrenal corticotropic hormone mobilizes the
 appropriate hormones of both the adrenal cortex
(cortisol) and adrenal medulla (epinephrine).
 Released neurotransmitters diffuse across the synaptic
cleft, interact with postjunctional receptors, and produce
a postjunctional potential (either an EPSP, or an IPSP).
 Termination of the effect of the released
neurotransmitter.
1. At cholinoceptive sites, this occurs by metabolic inactivation by an
exceedingly efficient enzyme, acetylcholinesterase.
2. At adrenoceptive sites, the major mechanism is inactivation by
reuptake of the neurotransmitter into the presynaptic nerve terminal.
Sympathetic nerves recover approximately 87% of released NE by
this mechanism, although some metabolic inactivation also occurs.
Over 70% of this recovered NE is sequestered in synaptic vesicles.
Circulating catecholamines by contrast are cleared primarily by
nonneuronal mechanisms in the liver and kidney.The metabolism of
catecholamines is mediated primarily by the enzymes monoamine
oxidase (MAO) and catechol-O-methyl transferase (COMT). The
major metabolic products are 3-methoxy-4-hydroxyphenylethylene
glycol( MOPEG) and 3-methoxy-4-hydroxymandelic acid (VMA) .
 Steps in the metabolic disposition of catecholamines.
Norepinephrine and epinephrine are first oxidatively deaminated by
monoamine oxidase (MAO) to 3,4-dihydroxyphenylglycoaldehyde
(DOPGAL) and then either reduced to 3,4-dihydroxyphenylethylene
glycol (DOPEG) or oxidized to 3,4-dihydroxymandelic acid
(DOMA). Alternatively, they can be methylated initially by catechol-
O-methyltransferase (COMT) to normetanephrine and metanephrine,
respectively. Most of the products of either type of reaction then are
metabolized by the other enzyme to form the major excretory
products in blood and urine, 3-methoxy-4-hydroxyphenylethylene
glycol (MOPEG or MHPG) and 3-methoxy-4-hydroxymandelic acid
(VMA). Free MOPEG is largely converted to VMA. The glycol and,
to some extent, the O-methylated amines and the catecholamines may
be conjugated to the corresponding sulfates or glucuronides.
( Kirstein,2004;Axelrod, 1966).

Adrenergic and Cholinergic Agonists and their effects;

– Alpha adrenergic
• Increase vascular tone
• May decrease cardiac output
• May decrease regional blood flow (renal, spleen, cutaneous)
– Beta adrenergic
• Maintain blood flow
• May increase cellular metabolism
• May decrease immune system (Limbird,1988).
– Nicotinic receptors
• N1 or NM –They mediate skeletal muscles contraction.
• N2 or Nn-They play a major role in transmission of
cholinergic signals in the autonomic nervous system.
(Akah,2013).
- Muscarinic receptors
• M1.M4 and M5-muscarinic receptors found in the
CNS,where they mediate complex CNS responses like
 memory arousal,attention and analgesia
• M3 receptors-They produce responses to various smooth
muscles organs e.g in bladder,brochi, GIT,etc.(Akah,2013).

Table 1: Autonomic Receptor (Adrenergic) and their

effect.Adapted from (Unekwe,2015,Katzung,2007).
Receptor Location Effect
Alpha-1 Vascular wall Vasoconstriction Vascular wall
Adrenergic Vasoconstriction
Increase duration of
contraction without
Heart increased
chronotropy

Beta
↑Inotropy and
Adrenergic
Beta-1 Heart chronotropy
Beta 2 Blood vessels Vasodilation Vasodilation

Dopamine Vasodilation
Renal

Splanchnic

(mesenteric)

Coronary.cerebral
Table 2:
Autonomic
Receptor
cholinergic) and
their
effect.Adapted
from
(Unekwe,2015).
Conclusion
The concept of chemical substances mediating nervous activity at the autonomic
nervous system ,where there is established gaps/cleft was put forward by Du-
Bois Raymond in 1877. Autonomic nervous system helps to maintains
homeostasis by modulating the activity of visceral organs- smooth muscle,
cardiac muscle, and glands.
The vesicles of both cholinergic and adrenergic nerves contain primary
transmitters, namely; acetylcholine and noradrenaline respectively; they also
contain other substances in addition to the primary transmitters. They appear to
play several roles in the function of the nerves that release acetylcholine or
norepinephrine. They also participate in feedback inhibition of the same and
nearby nerve terminals.(Katzung,2007).
Otto Loewi (1921) provided the first proof of the chemical mediation of
synaptic transmission with his studies on the frog heart and its vagal
innervation in vitro. In 1926 Loewi and Navratil provided evidence that
"vagusstuff" was actually acetylcholine. Hence, Otto Loewi may aptly be
reffered to as the pioneer of the concept of modern neurohumoral
transmission.
Neurohumoral transmission is a dynamic process that involve the Passage of
electrical current along an axon in the form of an action potential , with a
resultant depolarization of nerve terminals and the release (by exocytosis)
of chemical substances called neurotransmitters into the synaptic (or
junctional) cleft.
Neurotransmitters released into the cleft diffuse to and interact with receptors
on postsynaptic neurons or effector cells to produce tissue excitation or
inhibition.
Reccomendations
1. More explicit research work should be done in area of Autonomic
Pharmacology,e.g.Study on the effects of sympathomimetic or
sympatholytic drugs and parasympathomimetic or parasympatholytic
drugs on different peripheralsystem..
2.Also,study on the selectivity of both the adrenergic and cholinergic
receptor subtypes will definitely be of immence value in the specific use
of these autonomic drugs in the treatment of different type of disease
conditions,such as in cardiovascular,renal,GIT, and central nervous
system disorders.
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APPENDIX I

Organ or Tissue function

Predominant
Adrenoceptor
Type
Adrenergic
Response
Muscarinic
Cholinergic
Response
HEART
Rate (chronotropic effect) β1 Increase Decrease
Ventricular contractile force
(inotropic effect)
β1 Increase Slight decrease
Conduction velocity (AV node) β1 Increase Decrease
EYE
Pupil size α1 Constriction of
radial muscle
causing dilation
(mydriasis)
Contraction of
circular muscle
causing
constriction
(miosis)
Accommodation β2 Relaxation of
ciliary muscle for
far vision
Contraction of
ciliary muscle
(lens thickens)
producing
accommodation
for near vision1
BRONCHIAL SMOOTH MUSCLE β2 Relaxation Contraction
Bronchial glands α1 ↓ Secretion Stimulation
β2 ↑ Secretion
BLOOD VESSELS (arteries and
arterioles)
Cutaneous α1, α2 Constriction No innervation3
Visceral α1
β2
Constriction
Minimal dilation
No innervation3
Pulmonary α1
β2
Constriction
Dialation6
No innervation3
Renal α1, α2 Constriction No effect
β1, β2 Minimal dilation7
Skeletal muscle α1
β2
Constriction
Dilation2
Coronary α1, α2
β1, β2
Constriction
Dilation4
No innervation3
cerebral α1 Constriction
VEINS α1
β2
Constriction
Dilation
No innervation
GASTROINTESTINAL TRACT
(tone, motility, and secretory
activity)
α,β Decrease increase
sphincters α1 Contraction relaxation
SPLENIC CAPSULE α1
β2
Contraction
Slight relaxation
No innervation
URINARY BLADDER
Detrusor muscle β2 Relaxation contraction
Trigone-sphincter muscle α1 Contraction Relaxation
UTERUS, pregnant β2
α
Relaxation
contraction
GLYCOGENOLYSIS
Skeletal muscle β2 Increase none
Liver α1,β2 Increase none
LIPOLYSIS α,β1,β38 Increase none
RENIN SECRETION β1
α
Increase
Decrease
None
INSULIN SECRETION α2
β2
Decrease