Autonomic Pharmacology 1 Flashcards
What are the 2 divisions of the peripheral nervous system?
autonomic and somatic
TRUE or FALSE: Only the autonomic nervous system has a sensory component.
FALSE: both autonomic and somatic nervous systems have a sensory component
The autonomic nervous system is under:
a) unconscious control
b) voluntary control
c) both
d) neither
a) unconscious control
The somatic nervous system is under:
a) unconscious control
b) voluntary control
c) both
d) neither
b) voluntary control
What are some disorders that autonomic drugs are used to treat?
heart disease
respiratory disease
glaucoma
nasal congestion
GI disorders
What are the divisions of the autonomic nervous system?
sympathetic, parasympathetic, intrinsic (enteric and intracardiac)
All nerves leaving the CNS use _____________ as a neurotransmitter.
acetylcholine (ACh)
If both nicotinic and muscarinic receptors are involved in a system, which one comes first and which one comes second in an efferent pathway?
first: nicotinic
second: muscarinic
What level(s) of the spinal cord do the preganglionic nerves emerge from in the sympathetic nervous system?
thoracic and lumbar levels of the spinal cord
Where are sympathetic ganglia found?
paravertebral sympathetic chains
What neurotransmitter and receptor is used by sympathetic PREganglionic fibres?
ACh and ganglionic nicotinic receptors (nAChR)
What is the main POSTganglionic neurotransmitter in the sympathetic nerves? What is the exception (NT and the receptor it acts on)?
main POSTganglionic NT in sympathetic nerves = noradrenaline
exception: ACh is the POSTganglionic NT in sympathetic nerves to sweat glands and it acts on MUSCARINIC receptors
What is the name of the cells in the adrenal medulla that release noradrenaline/adrenaline?
chromaffin cells
What is the difference between a DIFFUSE SYSTEM and a DIRECTED SYSTEM?
diffuse: continuously active, coordinated FIGHT OR FLIGHT response
directed: vegetative, digestion and secretion (REST AND DIGEST)
The sympathetic nervous system is a:
a) diffuse system
b) directed system
c) both
d) neither
a) diffuse system
The parasympathetic nervous system is a:
a) diffuse system
b) directed system
c) both
d) neither
b) directed system
TRUE or FALSE: A diffuse system is associated with sympathetic syndrome and a directed system is associated with parasympathetic syndrome.
FALSE: there is no “parasympathetic syndrome”
(note: it is true that a diffuse system is associated with sympathetic syndrome)
In general, the sympathetic nervous system is associated with smooth muscle ___________ but gut ___________.
Fill in the blanks with the words “contraction” or “relaxation”.
smooth muscle contraction
gut relaxation
Where in the brain does central sympathetic processing occur? (hint: 2 locations)
hypothalamus and medulla
What level(s) of the spinal cord do the preganglionic nerves emerge from in the parasympathetic nervous system?
sacral and cranial regions
Where are parasympathetic ganglia found?
target tissues
What neurotransmitter and receptor is used by parasympathetic PREganglionic fibres?
ACh on nAChR (nicotinic)
What is the main POSTganglionic neurotransmitter in the parasympathetic nerves and what receptor does it act on?
ACh on mAChR (muscarinic)
Where in the brain does central parasympathetic processing occur? (hint: same as sympathetic nervous system)
hypothalamus and medulla
What are the 2 branches of the enteric nervous system?
- myenteric plexus (of Auerbach)
- submucous plexus (of Meissner)
Sympathetic nerves provide an ____a_____ ____b____ input to the enteric nervous system.
Fill in the blank with:
a) inhibitory/excitatory
b) adrenergic/cholinergic
a) inhibitory
b) adrenergic
Parasympathetic nerves provide an ____a_____ ____b____ input to the enteric nervous system.
Fill in the blank with:
a) inhibitory/excitatory
b) adrenergic/cholinergic
a) excitatory
b) cholinergic
What are the 4 main neurotransmitters associated with the enteric nervous system?
ACh, 5-HT, ATP, Substance P
Explain the events that occur at cholinergic terminals, starting from synthesis to release from the terminal.
- Acetyl CoA synthesized in mitochondria
- Choline transported into nerve terminals via Na+-dependent carrier
- ACh synthesized in cytoplasm by CHOLINE ACETYL TRANSFERASE
- ACh transported into vesicles
- Vesicle fusion and Ca2+-dependent ACh release occurs
What substance blocks ACh release from the cholinergic terminals into the cleft?
botulinum toxin (botox)
What enzyme terminates the action of ACh?
acetylcholinesterase
mAChR are:
a) metabotropic
b) ionotropic
a) metabotropic
What are 2 indications that a receptor is metabotropic?
- heptahelical structure
- G-protein coupled
(note: heptahelical structure is synonymous with G-protein coupled)
Where are M1, M2, and M3 muscarinic receptors found?
M1 - neurons
M2 - cardiac
M3 - smooth muscle endothelial cells, glands
What are the 2 cascades that M1 and M3 act through? Draw them.
- Gq phospholipase C –> inositol triphosphate (IP3) –> Ca2+ channel activated –> phosphorylation of substrates
- diacyl glycerol (DAG) –> protein kinase C (PKC –> phosphorylate substrates
What is the overall effect of M3 agonists in endothelial cells that line the blood vessels? What is the cascade of events that occur?
Overall: relaxation of vascular smooth muscle and dilation of arterioles
- agonists binds to M3 and INCREASE Ca2+
- NO synthase activated
- NO released and diffuses into smooth muscle cells
- NO activates soluble guanylyl cyclase
- cyclic GMP generated
- relaxation of vascular smooth muscle and dilation of arterioles
What is the cascade of events that M2 receptors act through?
Gao/Gai –> bind to beta subunits –> open K+ channels (GIRK channels) –> inhibit adenylyl cylase activity –> reduce cAMP
Does M2 receptor binding cause hyperpolarization or depolarization? Would the effect be inhibitory or excitatory? Explain.
hyperpolarization and inhibitory b/c of the opening of K+ channels
nAChR are:
a) metabotropic
b) ionotropic
b) ionotropic
What 2 ions are nicotinic cholinergic receptors permeable to>
Na+ and K+
Does binding at nAChR cause hyperpolarization or depolarization?
depolarization
How many transmembrane subunits make up the nAChR ion channel?
5
What is the difference between the ganglionic and neuromuscular nicotinic receptors in terms of their subunits? Draw the receptors and note where the Ach binding sites are.
neuromuscular: 2 x alpha1, beta1, delta, epsilon
ganglionic: combinations of alpha and beta (NO alpha1, usually alpha3)
How many Ach binding sites are located on the nAChR?
2
Where on the subunits are the ACh binding sites found?
at the interface between subunits
