INTRODUCTION TO AUTONOMIC PHARMACOLOGY Part III - Mechanism

INTRODUCTION TO AUTONOMIC PHARMACOLOGY: Part III

Mechanism of neurotransmission atin the autonomic nervous system

General Features of PeripheralAutonomic Neurotransmission

NT = Neurotransmitter

General Features of PeripheralAutonomic Neurotransmission

Membrane Depolarization ofPre- or Postganglionic Fiber

Calcium Entry intoVaricosity

Exocytosis of NTDiffusion of NT AcrossNeuroeffector Junction

or Synapse

Activation of NT Receptors

Depolarization of Postganglionic Fiber or Response of

Effector Cell

Nerve Impulse

Sympathetic Postganglionic Fiber Effector Cell

Neuroeffector Junction

COMT

(Liver)

SUMMARY OF ADRENERGIC NEUROTRANSMISSSION

Summary of Catecholamine BiosynthesisTyrosine

DOPA

Dopamine

Norepinephrine

Epinephrine

ADRENALGLAND

SYMPATHETICNERVE

Parasympathetic/Sympathetic Preganglionic Fiber or

Parasympathetic Postganglionic Fiber

Neuroeffector Junction

Parasympathetic orSympathetic

Postganglionic Fiberor Effector Cell

SUMMARY OF CHOLINERGIC NEUROTRANSMISSSION

COTRANSMISSION

Release of More Than OneNeurotransmitter from the Same

Nerve Terminal

Cotransmitter B

Synergistic or Opposite Actions

Cotransmitter A

Types of Postsynaptic Synergism

Norepinephrine/NPY

Norepinephrine/ATP

Example of Postsynaptic Synergism:(NPY enhances actions of NE)

NPY 10 nMNE

NE

Per

fusi

on P

ress

ure

(m

mH

g)

Example of Postsynaptic Synergism:ATP mediates fast responseNE mediates slow responseControl

Prazosin

Prazosin +Suramin

Control

Suramin

Prazosin +Suramin

Many Examples of NANC Neurotransmitters

Many Examples of NANC Neurotransmitters

MODULATION OF NEUROTRANSMISSION

Modulation of Neurotransmisson

Presynaptic/Prejunctional Modulation

Postsynaptic/Postjunctional

Modulation

Presynaptic/Prejunctional

InhibitionPresynaptic/Prejunctional

Facilitation

Postsynaptic/Postjunctional

InhibitionPostsynaptic/Postjunctional Facilitation

MODULATION OF NEUROTRANSMISSION

From Nerve Terminal Being

Modulated(e.g.,

Autoinhibitory Feedback)

From Postsynaptic/Postjunctional

Site (e.g., Trans-synaptic/

Transjunctional Inhibitory Feedback)

From Nearby Nerve

Terminal (Cross-

talk)

From Remote Site via

Circulation(e.g., Renin

Release)

Sources of Modulators of

Neurotransmission

Mechanisms of Neuromodulation

NE Ach

NE

Ang II+

Mechanisms of Neuromodulation

Epi