Pharmacology Part 7 Flashcards
Give an overview of neurochemical transmission in the ANS?
- Uptake of precursor
- Synthesis of transmitter (T), or intermediate
- Storage of transmitter, or intermediate
- Depolarisation by action potential
- Ca2+ entry via voltage-activated Ca2+ channels
- Ca2+- induced release of transmitter (exocytosis)
- Receptor activation
- Enzyme-mediated inactivation of transmitter (cholinergic), or
- Reuptake of transmitter (adrenergic)
Give an overview of cholinergic transmissio?
- Uptake of choline via transporter (CHT). Rate limiting in synthesis of ACh
- Synthesis of ACh by choline acetyltransferase (ChAT). Acetyl coenzyme A (AcCoA) synthesised by mitochondria
- Storage of ACh within vesicle via transporter (VAChT). ATP and other anions are co-stored
- Depolarization of terminal by action potential
- Ca2+ influx through voltage-activated Ca2+ channels
- Ca2+- induced release of ACh from vesicles (exocytosis)
- Activation of ACh receptors (nicotinic, or muscarinic) causing cellular response
- Degradation of ACh to choline and acetate by acetylcholinesterase (AChE) – terminates transmission
- Reuptake and reuse of choline
Describe the structure of nicotinic acetylcholine receptors
> Consist of five glycoprotein subunits that form a central, cation conducting (Na+, K+ and Ca2+), channel
> Can be assembled from a diverse range of subunits (a1-10, B1-4, y, epsilon, delta)
What are the four well characterised ACh receptor subtypes?
Peripheral
>Skeletal muscle (a1)2Bgammaepsilon
> ganglionic
a3B4
CNS
>a4B2
>a7
What is (cholinergic) excitatory transmission at ganglia caused by
ACh released from preganglionic neurones that activate cation-selective nicotinic receptors of the postganglionic neurone cell body to elicit the rapid excitatory postsynaptic potential
What happens to postganglionic neurones in absence of excitatory synaptic input?
Silent
What are most postganglionic neurones innervated by?
sympathetic and parasympathetic are innervated by several presynaptic fibres
Is esps from one preganglionic input significant enough to trigger an action potential?
Yes but more generally simultaneous activity of several inputs is required
What do postganglionic and preganglionic fibres have in common?
utilize transmitters (e.g. peptides) other than ACh that may modulate ganglionic transmission
What is the predominant tome of the arterioles?
Sympathetic (adrenergic)
What is the predominant tone of the veins?
Sympathetic (adrenergic)
What is the predominant tone of the heart?
Parasympathetic (cholinergic)
What is the predominant tone of the iris, ciliary muscle, gi tract, unrinaty bladder and salivary glands?
Parasympathetic (cholinergic)
What is the predominant tone of the sweat glands?
Sympathetic (cholinergic)
How is blockade of cholinergic transmission at ganglia achieved?
> depolarization block by high concentrations of agonists (e.g. nicotine)
competitive antagonism (e.g. trimetaphan)
Non-competitive antagonism
What does hexamethonium do?
Blocks all ganglionic transmission (open channel block)
How does cholinergic transmission at parasympathetic neuro-effector junctions occur?
- Depolarization by action potential
- Ca2+ influx through voltage-activated Ca2+ channels
- Ca2+- induced release of ACh (exocytosis)
- Activation of muscarinic ACh receptor subtypes (M1 – M3) causing cellular response (tissue dependent)
- Degradation of ACh to choline and acetate by acetylcholinesterase (AChE) – terminates transmission
- Reuptake and reuse of choline
What does M1 GPCR couple with, stimulate and cause?
Gq
Phospholipase C
Increased acid secretion
What does M2 GPCR couple with, inhibit and cause?
Gi
Inhibition of adenylyl cyclase
Opening of K+ channels
Decreased Heart rate
What does M3 GPCR couple with, stimulate and cause?
Gq
Phospholipase C
Increased saliva secretion
Contraction of visceral and relaxation of vascular smooth muscle
Describe noradrenergic transmission at sympathetic neuroeffector junctions?
- Synthesis of NA (multiple steps)
- Storage of NA by transporter (concentrates)
- Depolarization by action potential
- Ca2+ influx through voltage-activated Ca2+ channels
- Ca2+-induced release of NA
- Activation of adrenoceptor subtypes causing cellular response (tissue dependent)
- Reuptake of NA by transporters uptake 1 (U1) and uptake 2 (U2)
- Metabolism of NA by monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT)
What branch of the nervous system are M cholinergic receptors?
Parasympathetic
What does B1 GPCR couple with, stimulate and cause?
Gs
Adenylyl cyclase
Increased HR and force
What does B2 GPCR couple with, stimulate and cause?
Gs
Adenylyl cyclase
Relaxation of bronchial and vascular smooth muscle
