Introduction to PERIPHERAL NERVOUS SYSTEM Pharmacology

Anatomy of the Peripheral Nervous System

The nervous The peripheral nervous system system (PNS) further is divided intois the divided nervous central into the system and afferent (CNS) NS bringing the peripheral information from the nervous peripherysystem to the CNS (PNS). and

efferent NS carrying signals away from the CNS to the peripheral tissues.

The efferent NS is further divided into the autonomic nervous system (ANS) and somatic motor nervous system

 The somatic motor nervous system innervates skeletal muscles which receive only one efferent neuron.

The ANS is further divided into sympathetic and parasympathetic nervous systems
The autonomic nervous system innervates viscera such as heart, smooth muscle, and glands etc.
Target tissues receive two types of efferent neurons, sympathetic and parasympathetic nerves.

There are ganglia between the CNS and the effectors innervated by autonomic nerve system.
Preganglionic fiber, ganglion, postganglionic fiber

Neurotransmitter Chemistry of ANS

The classification of efferent nerves is based on the transmitter--acetylcholine (ACh)or norepinephrine (NE) released from their terminals.
1) Cholinergic fibers: It is fibers releasing ACh 2) noradrenergic fibers: NE 3) Other fibers:

1) Cholinergic fibers include:

somatic motor fibers, 2) noradrenergic fibers:

Cholinergic fibers:

postganglionic sympathetic Most preganglionic autonomic fibers, fibers release It is fibers norepinephrine. They are noradrenergic fibers. releasing parasympathetic fibers,
a few sympathetic postganglionic fibers (controlling sweat gland and blood vessel in skeletal muscle)

ACh 3) Other fibers: release adrenaline, dopamine and peptides.

nervous fibers
controlling adrenal medulla.

Chemical Transmission in Autonomic NS Transmitter: Synapse: It thejunction chemical It is is the of nerve

terminal with the next agent released from neuron terminal or effector cell, nerve that consisting of presynaptic transmits information membrane, postsynaptic across synapse and membrane and synaptic to effectors. space.
pre post Synapse

This triggers the fusion of The transmitters diffuse Action potential across the cleft and bind APpassing vesicles containing down an axon to the neurotransmitters and cell to receptors on the axon terminal membrane, and causes thepostsynaptic membrane changes membrane release of neurochemical to induce a response in the postsynaptic neuron. polarization (neurotransmitter) into the synaptic cleft.

resulting in Ca2+ entry into the cell.

Chemical Transmission in synapse

Cholinergic Transmission
ACh is synthesized from acetyl coenzyme A (Ac-CoA) and choline through the catalytic action of choline acetyl transferase (ChAT).

Choline is transported into the presynaptic nerve terminal by a carrier (A)

Once synthesized, ACh is transported into and packaged in the vesicles.

Cholinergic Transmission
After release, ACh bind to and activate pre- and postsynaptic acetylcholine receptors (cholinocept or), showing the action of transmitter.

When an AP reaches the terminal and triggers influx of Ca2+ which facilitates the fusion of the vesicular membrane with the terminal membrane and results in the release of ACh into synaptic space.

Then, ACh is hydrolyzed rapidly by acetylcholinesterase (AChE), terminating the action of the transmitter.

Cholinergic Transmission
Fig. Action potentialinduced release of the neurotransmitter acetylcholine (ACh) and its metabolism at the neuromuscular junction.

Adrenergic Transmission
.

Tyrosine is transported actively into the Dopa is noradrenergic ending decarboxylated to and is converted to dopamine by dopa by tyrosine dopa hydroxylase decarboxylase. Dopamine is transported into the vesicles and then converted to NE by dopamine-betahydroxylase. In the
adrenal medulla, NE is further converted to epinephrine.

An action potential causes an influx of Ca2+ into the nerve terminal, fusion of the vesicle with the plasma membrane and exocytosis of NE.
The transmitter then activates receptors in the postsynaptic membrane.

NE in the synaptic space is actively reuptaken into the nerve and the storage vesicles (uptake l). It is the most important NE penetrates into mechanism for smooth cells of (uptake termination the 2) and diffuses away action. from the receptor site, is inactivated by COMT (enzyme) to normetanephrine (NMN).

Another portion of the NE reuptaken into the nerve is deaminated by MAO enzyme .

NE can also activate presynaptic (2) receptors, to inhibit further release of NE.

Autonomic Receptors
Receptor: The

G protein-coupled receptor

receptive substances (protein) of a cell that specificly bind, interact 5-HT M- with ligands, and transmit information.
A C G DNA

Receptors of autonomic nerve system include cholinoceptors, adrenoceptors and dopamine receptors

1 Cholinoceptors :
The receptors combined with ACh are classified as muscarinic and nicotinic receptors.

2 Adrenoceptors
The receptors combined with NE and adrenaline include two groups

Receptors Function
Most of organs are innervated by both of the sympathetic and parasympathetic nervous system. The two systems generally have opposing effects. But, they are uniform in vivo

1) Sympathetic activity Both NE and Ad bind to -adrenoceptors, -adrenoceptors and induce respective effects.

(1) Vascular constriction of skin, splanchnic, and mucosa increases blood pressure. (2) Radial muscle of iris contracts to dilate pupil (mydriasis). (3) Contracting sphincters of gastrointestinal tract and urinary bladder. (4) Secretion of sweat glands in palms of hands. (5) Glycogenolysis of liver increase blood sugar.

1. Effects of

2) 1 effects 2 () enhancing the force, rate and (1) Cardiac stimulation 4 conduction of the heart. 1 (2) Renin secretion.

3) 2 effects 2 (1) Dilatation of artery in skeletal muscles and the heart. (2) Relaxation of bronchus, gastrointestinal and 2 genitourinary smooth muscle. 33 (3) Glycogenolysis and gluconeogenesis of liver.
4

4) 3 effects lipolysis of fat cells.

metabolic

2. M effects: 1) Inhibiting heart (M2) to decrease heart rate, conduction and contractility. 2) Vasodilation of artery 3) Contraction of bronchial, gastrointestinal and genitourinary smooth muscles, but relaxation of sphincters 4) Increasing secretion (M3) of salivary, respiratory and gastrointestinal tract glands 5) Eye (M3): miosis. near vision.

3. Dopamine Dl D2

receptors

There are 5 subtypes of dopamine receptors. Dl receptor is the most important. It locates in vascular smooth muscle cells, brain etc. It can dilate blood vessel, decrease peripheral vascular resistance and increase urinary volume.

Drug Classification of ANS

1. Effects on Receptors 1) Agonist (high intrinsic activity) cholinoceptor-activating drugs M and N receptor agonist: ACh M receptor agonist: Pilocarpine N receptor agonist: Nicotine adrenoceptor-activating drugs and receptor agonist: Adrenaline agonist. NE agonist: Isoprenaline

2) Antagonist (no intrinsic activity) cholinoceptor-blocking drugs M receptor blocker: atropine N1 receptor blocker: hexamethonium N2 receptor blocker: tubocurarine adrenoceptor antagonist drugs

receptor blocker: phentolamine 1 receptor blocker: prazosin receptor blocker: propranolol andreceptor blocker: labetolol

2. Influencing transmitters
1) Influencing metabolism of ACh Anticholinesterases: Neostigmine (cholinomimetics) Cholinesterase reactivators: PAM (anticholinergics) 2) Influencing transportation of NE

Sympatholytics: Reserpine: inhibit uptake of NE

from synapse to vesicles and prevent storage depletion of vesicles

release of NE

BP
releasing NE

Adrenergics: Ephedrine