Autonomic Pharmacology I Flashcards
Nervous system and subdivisions?
Nervous system can be divided into:
CNS (brain and spinal cord)
PNS:
Somatic NS
Somatic efferent supply skeletal muscle, for example
Somatic and visceral afferent
Enteric (ENS) - part of ANS but is within walls of GI tract, allowing regulation of gut function (largely independent of rest of NS)
Autonomic (ANS) - sympathetic and parasympathetic division
Difference between afferent and efferent?
Afferent - towards CNS
Efferent - away from CNS
Over all functions of the ANS?
Responsible for carrying output from CNS to whole body, with EXCEPTION of skeletal muscle
Regulates visceral functions that are largely INVOLUNTARY, e.g:
Contraction/relaxation of vascular and visceral smooth muscle
All exocrine and certain endocrine secretions
Heartbeat
Aspects of metabolism, part. liver and skeletal muscle)
Control of ANS?
Training allows a degree of control of some ANS functions, e.g: urination, defecation
Sympathetic and parasympathetic subdivisions of ANS?
Often work in an opposing fashion to maintain homeostasis
Parasympathetic ANS - coordinates body’s basic homeostatic functions, sedentary and “rest and digest”
Sympathetic ANS - coordinates body’s response to stress, associated with fight/flight reactions
What is a ganglion?
Collection of nerve cell bodies in the PNS; CNS equivalent is a nucleus
Transmitters in sympathetic division?
Preganglionic neurones (cholinergic) - acetylcholine (ACh)
Postganglionic neurones (usually adrenergic) - noradrenaline
Transmitters in parasympathetic division?
Preganglionic neurones (cholinergic) - acetylcholine
Postganglionic neurones (cholinergic) - acetycholine
Describe the sympathetic outflow
Sympathetic nerves in lateral horns of spinal cord (T1-L2) - AKA thoracolumbar outflow
Describe the parasympathetic outflow
Cranial nerves 3, 7, 9 and 10
Cranio-sacral outflow
Where do pre- and post-ganglionic neurones synapse?
Prevertebral ganglia
Paravertebral ganglia
Where are parasympathetic ganglia normally?
In target organs, e.g: discrete ganglia in head and neck
Effect of ANS on organs?
Sympathetic stimulation:
Increases HR
Increases force of contraction
Relaxes bronchi (via release of adrenaline) Decreases mucous production (decreases airway resistance)
Reduces motility
Constricts sphincters
Constricts in most location but relaxes in skeletal muscle
Release of adrenaline from adrenal glands
Ejaculation
Parasympathetic stimulation:
Decreases HR
Constricts bronchi
Stimulates mucous production (increases airway resistance)
Increases motility
Relaxes sphincters
Largely no effect
No effect on adrenal gland
Erection
How does neurochemical transmission occur?
- Uptake of transmitter precursor into neuron
- Synthesis of transmitter
- Storage of transmitter in vesicle
- DEPOLARISATION by action potential
- Ca2+ INFLUX through voltage-activated Ca2+ channels
- Ca2+ binds to the vesicle causing Ca2+ induced release of transmitter (exocytosis)
- Receptor activation
- Enzyme-mediated inactivation of transmitter
OR
Re-uptake of transmitter
Fates of different neurotransmitters?
Acetylcholine - enzyme-mediated degradation
Noradrenaline - re-uptake of transmitter in pre-synaptic cell or in non-neurone cell
Describe chemical transmission in the sympathetic division of the ANS
Action potential originating in the CNS:
Travels to pre-synpatic terminal of the preganglionic neurone triggering Ca2+ entry and the release of ACh
ACh open LIGAND-GATED ION CHANNELS (NICOTINIC ACh receptors) in the postganglionic neurone, causing depolarisation and action potential generation, which travel to presynaptic terminal of neurone, triggering Ca2+ entry and the release of NORADRENALINE
Noradrenaline activates G-protein coupled ADRENOCEPTORS in the target cell membrane to cause a CELLULAR RESPONSE
Describe chemical transmission in the parasympathetic division of the ANS
Process is identical to that for the sympathetic division, with exceptions:
ACh is always the transmitter used by postganglionic neurones
ACh activates G-protein coupled MUSCARINIC ACETYLCHOLINE receptors in the target cell membrane, to cause a cellular response
Structure of ligand-gated ion channels?
Consist of separate glycoprotein subunits that form a central, ion conducting channel
There are transmitter binding sites between the subunits
Function of ligand-gated ion channels?
Allows rapid changes in the permeability of the membrane to certain ions
Rapidly alter membrane potential
How do ligand-gated ion channels work?
Agonist binds
Channel opens
Ion flow
Describe G-protein coupled receptors
E.g: Muscarinic ACh receptors
Receptor, G-protein and effector are separate proteins
G-protein couples receptor activation to effector modulation
Signalling via G-proteins is slow in comparison to ligand-gated ion channels
Structure of G-protein coupled receptors?
Integral membrane protein
Single polypeptide with extracellular NH2 and intracellular COOH termini
Contain 7 transmembrane proteins joined by 3 extracellular and 3 intracellular CONNECTING LOOPS
Structure of G-proteins?
AKA Guanine nucleotide binding protein)
Peripheral membrane protein
Consists of 3 polypeptide subunits (α, β and γ)
Contains a guanine nucleotide binding site in the α-subunit that can hold guanosine triphosphate (GTP) or guanosine diphosphate (GDP)
Describe G-protein coupled receptors when there is no signalling
Receptor is unoccupied
G-protein α-subunit binds GDP
Effector is not modulated
Describe G-protein coupled receptors when the signal is being turned on
Agonist activates the receptor and G-protein couples with this
GDP dissociates from the α-subunit and GTP binds to it
G-protein dissociates into separate α, β and γ subunits
G-protein α-subunit combines with, and modifies, the activity of the effector
Agonist may dissociate from the receptor but the signal can persis
Describe G-protein coupled receptors when the signal being turned off
α-subunit acts as an ENZYME (a GTPase) to hydrolyse GTP to GDP and Pi.
Signal is turned off
G-protein α-subunit recombines with the βγ-subunit, completing the “G-protein cycle”
