L7. Pharmacological overview of the peripheral nervous system Flashcards
What is the difference between the peripheral and central nervous systems?
The CNS involves the brain and cranial nerves and afferent sensory information while the PNS involves the peripheral body: efferent signals going down to affect the voluntary and autonomic parts of the body
What is the major site of pharmacological manipulation for the PNS?
The synapses between the terminals and the effector cells
- Action potential
- Neurotransmitter formation
- Storage of neurotransmitters
- Release (exocytosis)
- Receptor binding and post-membrane signalling
- Uptake or breakdown of the neurotransmitter
- Metabolism of the neurotransmitters
How is the Peripheral Nervous System organised?
Involuntary innervation (autonomic nervous system) which innervates most organs and tissues of the body Sympathetic: short preganglionic and long post-ganglionic Parasympathetic: long pre-ganglionic and short post-ganglionic Somatic: single fibre systems that innervate skeletal muscles (voluntary)
What are the two most important transmitters in the peripheral nervous system?
- ACh (cholinergic)
2. Noradrenaline and adrenaline (adrenergic) - sympathetic NS
Describe the synthesis of ACh
Acetyl-CoA is synthesised in the mitochondria while the choline in the extracellular fluid is transported in through the choline transporter.
Choline-acetyltransferase facilitates the formation of ACh and CoA from these two substrates
The ACh is packaged into synaptic vesicles through transport via a ACh carrier
How is the action of ACh in the junctions ceased?
ACh is released by exocytosis after an action potential and the ACh is able to act on the receptors of the effector cells.
The enzyme ACh Esterase (AChE) is tethered to the post-junctional membrane and breaks down ACh into Choline and acetate.
The choline is taken back into the cell for recycling
Describe the synthesis of noradrenaline
Tyrosine (an abundant amino acid) enters the cell and through the action of tyrosine hydroxylase gets converted in L-DOPA.
DOPA carboxylase then acts on L-DOPA converting it into dopamine.
Dopamine is then transferred into the vesicles and the action of dopamine Beta hydroxylases into noradrenaline.
In some cells Phenylethanolamine-N-methyl transferases PMNT convert noradrenaline to adrenaline
How is the action of noradrenaline/adrenaline in the junctions ceased?
A channel called the Neuronal High Affinity Uptake-1 on the presynaptic cell transports the noradrenaline back into the pre-synaptic cell takes noradrenaline up and repackages it.
Additionally the Extraneuronal Low Affinity Uptake-2 channel also takes up noradrenaline out of the cleft and into the post-synaptic cell.
What ways is the action of Noradrenaline increased?
EG. Cocaine and other Tricyclic anti-depressants block the Neuronal High Affinity Uptake-1 leading to increased action of noradrenaline/dopamine/adrenaline in the synapse.
What is meant by co-transmission?
Co-transmission is where co-transmitters are released together to allow a modulation and fine-tuning of the action of the major dominant transmitter.
May also be the cause of 2 phase responses.
What are the two cholinergic receptors in the body, where are they found, what kind of receptors are they and what are major antagonists of them?
Nicotinic found at the ganglionic sites and at the skeletal muscle junctions.
These are ligand gated and ATROPINE is the antagonist
Muscarinic receptors are found at the post-ganglionic transmission to tissues for parasympathetic innervation.
These are GPCRs and CURARE (dTC) is the major antagonist
What are the major receptors for adrenaline? What kind are they and where are they localised?
Alpha and Beta adrenoreceptors
Alpha 1: Smooth muscle cells of the peripheral vaculature (contraction)
Alpha 2: CNS and presynaptic nerves (analgesia, relaxation and hypotension)
Beta 1: Heart and Juxtoglomerular cells (increase HR and contractility)
Beta 2: RT smooth muscle cells (bronchorelaxation)
