Neurotransmission & ANS Pharmacology I: Neurotransmission & Drug Targets in the ANS Flashcards
Where do Sympathetic nerves in the ANS originate?
Thoracic area of spine
Do Sympathetic nerves of the ANS have long or short PRE-GANGLIONIC neurons?
Short
Where do Parasympathetic nerves in the ANS originate?
- Cranial nerves
- Lumbar / Sacral areas of spine
Do Parasympathetic nerves of the ANS have long or short PRE-GANGLIONIC neurons?
Long
Which of the ANS nerve type synapses directly into the wall of an organ or tissue?
Parasympathetic
What functions do the Parasympathetic nerves control?
- Salivation
- Lacrimation
- Urination
- Digestion
- Defecation
SLUDD
Is the Parasympathetic system anabolic or catabolic?
Anabolic
* conserves and stores energy
What response is controlled by the Sympathetic nerves?
Fight or Flight
Is the Sympathetic system anabolic or catabolic?
Catabolic
* mobilises energy, raises blood pressure, body temperature, dilate airways etc
What are the TWO main neurotransmitters in the ANS?
- ACh
- Noradrenaline
What is the general sequence of events for neurotransmitters?
- Synthesis
- Storage Release
- Recognition
- Metabolism / Reuptake
What are the the steps in Cholinergic transmission?
- Choline (re)uptake
- ACh synthesis in cytosol
- ACh accumulation into synaptic vesicles
Which transport protein drives Choline (re)uptake in Cholinergic neurotransmission?
Na+ driven Symporter
Which enzyme synthesises ACh?
Choline Acetyltransferase
Which transport protein drives ACh into synaptic vesicles in Cholinergic neurotransmission?
H+ driven Antiporter
Where are nACh receptors located?
- Autonomic ganglia
- Adrenal medulla
- Neuromuscular junction
Where are mACh receptors located?
Autonomic effector cells
What are the THREE subtypes of Muscarinic receptors?
- M1 - neural
- M2 - cardiac
- M3 - glandular
What is the mechanism of nACh receptors?
Open cation channels that leads to membrane depolarisation
What type of transmission are nACh receptors involved in?
- Neuromuscular
- Ganglionic
What is the mechanism of the M1 muscarinic receptor?
- INCREASE in IP3 and DAG
- Excitation
What is the mechanism of the M2 muscarinic receptor?
- DECREASE in cAMP
- Inhibition
What is the mechanism of the M3 muscarinic receptor?
- INCREASE in IP3 and DAG
- Excitation
Where are Muscle Type Nicotinic receptors located?
Skeletal NMJ
How do Muscle Type Nicotinic receptors work?
Membrane depolarisation via Na+ channel opening, leading to NMJ transmission
Where are Neuronal Type Nicotinic receptors located?
Autonomic ganglia
How do Neuronal Type Nicotinic receptors work?
Open fast Na+ channels, leading to ganglion transmission
What are THREE Agonists of Muscle Type Nicotinic recptors?
- ACh
- Suxamethonium
- Decamethonium
What are TWO Antagonists of Muscle Type Nicotinic recptors?
- Vecuronium
- Pancuronium
What are THREE Agonists of Neuronal Type Nicotinic recptors?
- ACh
- Nicotine
- Epibatidine
What are TWO Antagonists of Neuronal Type Nicotinic recptors?
- Trimetaphan
- Hexamethonium
Which amino acid does Acetylcholine Esterase act on?
Serine
What are the THREE hydrolysis products of Acetylcholine Esterase?
- Choline
- Acetic Acid
- Regenerated Enzyme
What are the molecules transformed in the synthesis of Adrenaline?
- Tyrosine
- DOPA
- Dopamine
- Noradrenaline
- Adrenaline
What enzyme converts Tyrosine to DOPA?
Tyrosine Hydroxylase
What enzyme converts DOPA to Dopamine?
DOPA Decarboxylase
What enzyme converts Dopamine to Noradrenaline?
Dopamine β-hydroxylase
What enzyme converts Noradrenaline to Adrenaline?
Phenylethanolamine N-methyltransferase
Which drugs block the reuptake of of noradrenaline into presynaptic cells?
- Cocaine
- Tricyclic antidepressants
Which Adrenoceptors act in the heart, intestine, and smooth muscle, and which secondary messenger do they modulate?
- β1
- INCREASE cAMP
Which Adrenoceptors act in the bronchial, vascular, and uterine smooth muscles, and which secondary messenger do they modulate?
- β2
- INCREASE cAMP
Which Adrenoceptors act in the postsynaptic cell, and which secondary messenger do they modulate?
- α1
- INCREASE IP3 / DAG
Which Adrenoceptors act in the presynaptic cell, and which secondary messenger do they modulate?
- α2
- DECREASE cAMP
How are Adrenoceptors activated (agonised)?
By noradrenaline, adrenaline, and dopamine (catecholamines)
What are the FOUR major effects mediated by the α1 Adrenoceptor?
- Vasoconstriction
- Relaxation of GI smooth muscle
- Salivary secretion
- Hepatic glycogenolysis
What are the FOUR major effects mediated by the α2 Adrenoceptor?
- Inhibition of transmitter release (NA & ACh)
- Inhibition of vascular smooth muscle contraction
- Inhibition of insulin release
- Inhibition of platelet aggregation
What are the TWO major effects mediated by the β1 Adrenoceptor?
- Increased cardiac rate
- Increased force
What are the FIVE major effects mediated by the β2 Adrenoceptor?
- Bronchodilation
- Vasodilation
- Relaxation of visceral smooth muscle
- Muscle tremor
- Hepatic glycogenolysis
