ANS..???

Autonomic Nervous System

 Nervous
system

CNS PNS

Autonomic Somatic

Symp Parasymp Enteric

 SOMATIC AUTONOMIC
Organ supplied Skeletal muscle Other organs

Distal most synapse

Within CNS Outside CNS

Preganglionic -
Nerve fibre Myelinated myelinated
Post ganglionic – non
myelinated
Peripheral plexus Absent Present
Formation

Efferent transmitter Ach Ach, NA

Effect of nerve section Paralysis and Activity maintained : no

on organ supplied Atrophy atrophy
 Differences between sympathetic and
parasympathetic systems
Sympathetic Parasympathetic

Origin Dorso- lumbar Cranio – sacral

Distribution Wide Limited to head,

neck,trunk

Ganglia Away from organs On or close to organs

Pre: post ganglionic 1:20 1:1

fibre ratio

Postganglionic fibres Long Short

Transmitter Na (major) Ach (minor) Ach

Neurohumoral transmission
Nerves transmit their message across synapses
and neuroeffector junctions by release of humoral
(chemical) messengers
 Otto Loewi -1921

Vagusstuff of Dale

1926 – Vagusstuff was Ach

A neurotransmitter should possess following features

9 It should be present in the presynaptic neurons 

9 It should be released following the nerve stimulation

9 Its application produces responses similar to those produced 
by nerve stimulation

9 Its effect should be blocked or potentiated by the substance 
which similarly alter the effect of nerve stimulation     
STEPS IN NEUROHUMORAL TRANSMISSION

ƒ Impulse conduction 

ƒ Transmitter release

ƒ Action on the postjunctional membrane

ƒ Postjunctional activity

ƒ Termination of transmitter action 
????
Adrenaline
Adrenergic System & Drugs

Dr Satyajit
Catecholamines ????
 “Catechol”

1,2 dihydroxybenzene
Most abundant endogenous 
catecholamines

9 Adrenaline / Epinephrine

9 Noradrenaline / Norepinephrine

9 Dopamine
Adrenaline Dopamine

Noradrenaline
Noradrenaline
post ganglionic sympathetic sites (sweat glands, 
hair follicles)

Adrenaline
Adrenal medulla, transmitter in brain

Dopamine
Major transmitter in basal ganglia, limbic system,    
CTZ, anterior pituitary 
Synthesis of catecholamines
 Phenylalanine
Hydroxylase Liver
Tyrosine
Hydroxylase
DOPA Adrenal neuronal cytoplasm
Decarboxylase
Dopamine
ß Hydroxylase Inside granules

Noradrenaline
Methyl transferase Adrenal medulla cells
Adrenaline
 Synthesis of NA/NE occurs in ‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐???

ƒ Adrenaline  occurs only in ‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐??
Storage of catecholamines
 Noradrenaline

ƒ Synaptic vesicles within adrenergic nerve endings

ƒ Vesicular membrane actively takes DA

ƒ Dopa decarboxylase

ƒ NA forms a complex with ATP (4:1)

ƒ Adsobed to chromagranin
 Adrenaline

ƒ In adrenal medulla, NA is diffused to cytoplasm

ƒ Methylation – N‐methyl transferase

ƒ NA ‐‐‐‐‐‐‐> Adrenaline
Release of catecholamines
ƒ Release of CA occur by exocytosis

ƒ All components (NA, Adr, ATP,dopamine hydroxylase)

ƒ Co transmitters

ƒ Indirectly acting sympathomimetic ???
9 Displace NA from nerve binding site
9 Exchange diffusion by NET
Uptake of catecholamines
 Axonal Uptake
9 Uptake 1

9 Active amine pump (NET)

9 Transports NA by Na+ coupled mechanism

9 Takes NA more than Adr

9 Most important in terminating action of NA

9 Inhibited by Cocaine, desipramine
 Vesicular uptake
ƒ VMAT‐2 (vesicular monoamine transporter)

ƒ Transports NA from cytoplasm to vesicles

ƒ Exchange with H+ ion

ƒ Takes dopamine for synthesis of NA

ƒ Maintain the conc of NA

ƒ Inhibited by reserpine
 Uptake 2
9 Extra neuronal uptake

9 Extra neuronal amine transporter (ENT), OCT

9 Take Adr more than NA

9 Not Na+ dependent

9 Not inhibited by Cocaine

9 No pharmacological importance
Metabolism of catecholamines
DOPGAL : 3,4 dihydroxyphenylglycolaldehyde
DOPEG: 3,4 dihydroxy phenylethylene glycol
DOMA: 3,4 dihydroxy mandelic acid
MOPEG : 3 methoxy 4 hydroxy phenylethyleneglycol
 Excretion
9 Metabolites excreted in urine is VMA, MOPEG, 
DOMA

9 Mostly conjugated with glucuronic acid or sulfate 
before excretion

9 Only 2‐5 mic gm of Adr and 25‐50 mic of NA excreted 
in free form in 24 hrs
Adrenergic receptors
Raymond Ahlquist , 1948
 Types of Adreno receptors
ƒ 2 types

¾ α receptors

¾ ß receptors
9 Membrane bound GPCR

9 Increase or decrease the cAMP or IP3 /DAG

9 Operates K+ or Ca+ channel

 α ß
Order of potency Adr ≥ NA >Iso Iso > Adr >NA
of agonist

Antagonist Phenoxybenazmaine Propranolol

Effector pathway ↑IP/DAG3 ↑cAMP,

↓cAMP , ↑Ca+ channel
↑ K+ channel
 Beta receptor ‐ ß
ƒ Organ specificity of agonist and antagonists

¾ ß1
¾ ß2
¾ ß3
 Beta receptor – ß1

ƒ Heart

ƒ JG cells of kidney

ƒ Agonist‐ Dobutamine

ƒ Selectivity : Adr = NA

ß1
↑Cardiac stimulation, ↑rate, force and conduction
 Beta receptor – ß2

ƒ Smooth muscle : bronchus

ƒ GU, Intestine

ƒ Uterus

ƒ Urinary tract

ƒ Eye

ƒ Agonist : salbutamol, terbutaline

ƒ Selectivity : Adr > NA
 ß2 ß2
↑Bronchodilatation Relaxation
 ß2
Relaxation
 Beta receptor – ß3

ƒ Adipose tissue

ƒ Affinity : NA

ƒ Agonist – antiobesity drugs
 Alpha receptor – α

ƒ α1

ƒ α2

ƒ α3

α 1A, α 1B, α 1D α 2A, α 2B, α 2C

 Alpha receptor – α1
ƒ Post junctional effector organ

ƒ Vasoconstriction

ƒ GU smooth muscle ‐ contraction

ƒ Gland ‐ secretion

ƒ Gut ‐ relaxation

ƒ Agonist: Phenylephrine

ƒ Antagonist ‐ Prazosin
α1
 Alpha receptor – α2
ƒ Pre junctional nerve endings  (α2A)

ƒ Post junctional – Brain, pancreatic beta cells

ƒ Inhibition of transmitter release

ƒ Decrease central sympathetic outflow

ƒ Decrease insulin release

ƒ Agonist: Clonidine

ƒ Antagonist ‐ Yohimbine
Organ αAction ß action
Blood vessels Constriction (α1) Dilatation (ß2)
(arterioles and
veins)
Heart Little action Stimulation (ß1)

Eye Radial muscle (α1) No effect

Intestine Relaxation Relaxation

Uterus Contraction Relaxation

Splenic capsule Contraction relaxation

Dopamine receptors
 Remember…..

ƒ Catecholamine

ƒ Adrenoreceptors
Thank you