physiology and pharmacology of the autonomic nervous system

week 5 ct5b

ANS

• consists of 2 divisions:

  1. sympathetic system: fight or flight

  2. parasympathetic system: rest and digest

• enteric division: specialised network in GI tract controlled by sympathetic and parasympathetic fibres from CNS

2-synapse pathway

organisation of ANS

• preganglionic neurons are cholinergic-release acetylcholine (ACh)

• postganglionic neurons have N₂ nicotinic ACh receptors

• parasympathetic NS postganglionic neurons release ACh onto target organs

• sympathetic NS postganglionic neurons release noradrenaline onto target organs (apart from sweat glands ACh)

• adrenal medulla receives direct innervation from sympathetic preganglionic neuron

dual innervation

• most organs receive input from both parasympathetic and sympathetic divisions

• parasympathetic and sympathetic divisions have opposing effects

• organs activated during physical activity: sympathetic stimulates, parasympathetic inhibits

• organs activated at rest: parasympathetic stimulates, sympathetic inhibits

• some exceptions:

  • salivary glands

  • sweat glands

  • peripheral blood vessels

sympathetic neurotransmission

• synthesis

  • tyrosine converted to dopa by tyrosine hydroxylase

  • dopa converted to dopamine by dopa decarboxylase

  • dopamine transported into vesicles

• storage

  • dopamine converted to noradrenaline (norepinephrine) in vesicles

• release

  • noradrenaline released via Ca2+ dependent exocytosis

• receptor activation

  • noradrenaline binds to adrenoreceptors to elicit response in target cell

• inactivation

  • noradrenaline uptake from synaptic cleft

sympathetic receptors 1

• beta adrenoceptors are G-protein linked receptors

• beta adrenoceptors activate adenylyl cyclase

• intracellular cAMP levels are increased

• adenylyl cyclase converts ATP to cAMP

• cAMP activated protein kinase A (PKA)

sympathetic receptors 2

• alpha 1 adrenoceptors activate phospholipase C (PLC) via G protein

• PLC breaks down PIP2 to form DAG and IP₃

• liberated DAG activates protein kinase C (PKC)

• liberated IP₃ stimulates Ca2+ release from intracellular stores

sympathetic receptors 3

• alpha 2 adrenoceptors activate an inhibitory G protein

• adenylyl cyclase is inhibited

• intracellular cAMP levels are decreased

summary of adrenoreceptors

sympathetic effects on major organ systems: cardiovascular