Introduction to Autonomic Pharmacology Flashcards
The nervous system is divided into the
CNS and the PNS
The peripheral nervous system is subdivided into the
autonomic NS and the somatic NS
The autonomic nervous system is subdivided into the
sympathetic NS and the parasympathetic NS
Parasympathetic neurons respond to
acetylcholine
Parasympathetic neurons are called
cholinergic neurons
Sympathetic neurons are activated by
endogenous NE and Ep (adrenaline and noradrenaline)
Sympathetic neurons are known are
adrenergic neurons
Describe the anatomical pathway that sympathetic fibers take to get to their targets?
sympathetic preganglionic fibers leave the CNS through the thoracic and lumbar spinal nerves, most preganglionic nerves are short and terminate in the vertebral ganglia, the longer postganglionic sympathetic nerves then run to the tissues innervated
Sympathetic neurons are known are
adrenergic neurons
Describe the anatomical pathway that parasympathetic fibers take to get to their targets?
parasympathetic preganglionic fibers leave the CNS through the cranial nerves in the medulla, the majority of long parasympathetic preganglionic nerves terminate in ganglion cells in the walls of the organs innervated, the postganglionic paraysmpathetic nerves are short
All preganglionic nerves release what, where?
release Ach onto post-ganglionic nerves expressing nicotinic cholinergic receptors (Nn)
The somatic nerve system motor neurons release what, where?
release Ach directly onto nicotinic cholinergic receptors expressed on skeletal muscle of organs (Nm)
Parasympathetic postganglionic nerves release what?
release Ach onto organs expressing muscarinic receptors (M)
Sympathetic postganglionic nerves primarily release what?
release NE that can bind to adrenergic receptors
Sympathetic postganglionic nerves innervating the skin release
release Ach acting on muscarinic receptors on thermoregulatory sweat glands
Postganglionic nerves innervating the kidney release
release dopamine (D) to bind to dopamine D1 receptors causing vasodilation
Separate postganglionic nerves that terminate in the adrenals cause what?
the release of Epi and to a lesser extent NE into the bloodstream
The primary source of Epi that acts on the heart and blood vessels?
postganglionic nerves that terminate in the adrenals
Acetylcholine receptors found post-synaptically
M1, M3, (M4), and M5
Acetylcholine receptors that are located pre-synaptically
M2 and M4
What do M2 and M4 function as?
inhibitory autoreceptors
What is Ach released from axons metabolized by and into?
metabolized by acetylcholinesterase and butylcholinessterase into acetate and choline
What transports choline back into the synapse
choline transporter (ChT)
How does choline acetyltransferase (ChAT) reform Ach?
ChAT transfers an acetyl group from acetyl-CoA to choline to reform Ach
How does Ach get taken back up into the synaptic vesicles?
taken back up into synaptic vesicles by vesicular acetylcholine transporter (vAchT)
Epinephrine receptors found post-synaptically
alpha1, beta1, beta2
Epinephrine receptors located pre-synaptically
alpha2 and beta2
Describe the synthesis of norepinephrine (NE)
NE is formed from tyrosine which is converted by tyrosine hydroxylase into DOPA, which is converted into dopamine by aromatic amino acid decarboxylase
Dopamine is transformed into NE by
dopamine beta-hydroxylase (taken up into vesicles to be released upon stimulation)
How is NE transported back into the synapse
by the norepinephrine transporter (NET)
What are the two different things that can happen to NE in the axon?
it can either be metabolized by monoamine oxidase (MAO) into dihydroxyphenylglycol or it can be taken up into vesicles by the vesicular monamine transporter (VMAT)
How is Ach taken back up into synaptic vesicles?
by vesicular acetylcholine transporter (vAchT)
Postsynaptically, NE is metabolized by what, into what?
metabolized by catechol-methyl-transferase (COMT) into normetanephrine
How do drugs influence the ANS?
either block or activate (mimic endogenous response) the adrenergic and cholinergic receptors
Cholinergic receptors can be subdivided into
nicotinic and muscarinic receptors
Nicotinic receptors are expressed in the
ganglia, CNS and skeletal muscles
Describe nicotinic cholinergic receptors
ion channels consisting of 5 subunits
Muscarinic receptors can be divided into
Gq-coupled (M1, M3, and M5) and Gi-coupled receptors (M2 and M4)
most common and most important muscarinic receptors in the parasympathetic nervous system
presynaptic M2 and post-synaptic M3
M2 is primarily located where?
in the heart and bladder, but can also be found in certain brain regions
M1, M4 and M5 are primarily located where
in the CNS
function of M5 receptor
causes vasodilation of cerebral blood vessels
Where are M3 receptors located
post-synaptically
Describe M3 receptors and what they do
Gq coupled causing increases in calcium and neuronal activation through a PLC mechanism
Where are M2 receptors located
pre-synaptically
What do M2 receptors do
inhibit neurotransmitter release by activating G-protein inwardly-rectifying potassium channels (GIRK) and by inhibiting voltage gated calcium channels (VGCC)
How do M2 receptors inhibit voltage gated calcium channels (VGCC)?
by Gi-mediated inhibition of adenylyl cyclase
Gi-mediated inhibition of adenylyl cyclase casues
a reduction in cAMP production, decreased protein kinase A activity and reduced calcium transport into the axon, thereby inhibiting neurotransmitter release
Adrenergic receptors are subdivided into
alpha1, alpha2, and beta subunits
alpha1 are
Gq-coupled
alpha2 are
Gi-coupled
beta subunits are
Gs-coupled
The adrenergic receptors primarily responsible for sympathetic responses are
alpha1 and beta receptors
Where are alpha2 receptors found primarily?
in the CNS but also the GI-tract and the pancreas
What kind of receptors do the muscles and cell bodies in the iris surrounding the lens contain?
muscarinic and adrenergic receptors
What kind of receptors do the radial muscles, also known as the dilator, contain?
alpha1
Activation of the alpha1 receptors on the radial muscles causes?
constriction of the radial muscles and dilation of the eye
The circular muscles (sphincter) contain
M3 and M3R receptors
What happens when M3 muscles on the sphincter (circular muscles) are activated?
the circle constricts and causes miosis
What does contraction of the ciliary muscles do?
changes accommodation, but also stretches the trabecular meshwork, which could reduce clogs on the Canal of Schlemm in open angle glaucoma
Beta receptors are expressed where, and do what?
beta receptors are xpressed in ciliary endothelium and increase secretion of aqueous humor
What happens when circular muscles of the iris contract?
pupil constricts
What happens when radial muscles of the iris contract?
pupil dilates
Pupil constriction is under what control?
the parasympathetic nervous system
Pupil dilation is under what control?
the sympathetic nervous system
Receptor that mediates contraction of circular muscles and pupil constriction
M3
Receptor that mediates contraction of radial muscles and pupil dilation
alpha1
two factors that control blood pressure
blood flow (Q) and resistance (R)
flow (Q) is equal to
stroke volume (SV) x heart rate (HR)
A drop in blood pressure due to severe loss of blood will trigger
an activation of the SANS (release of NE) and inhibition of the PANS (reduced Ach), this will lead to vasoconstriction, an increase in R, an increase in HR and SV, increasing Q
ANS responses on resistance (R) are mediated primarily by
vasoconstriciton through alpha1 receptors located in vascular smooth muscles
Activation of beta2 receptors on the skeletal muscle surrounding blood vessels causes
relaxation of the muscle and vasodilation
What do alpha1 and alpha2 near the junction of the vascular endothelial cells do?
respond to Ep in the blood stream and cause vasoconstriction
Activation of the non-innervated endothelial M3 receptors causes
release of nitric oxide, which will cause vasodilation by relaxing the vascular smooth muscle
In pathology where the endothelial cell is disrupted (ex. atherosclerosis) when happens with M3 activation?
M3 activation on smooth muscle wins and causes constriction of the smooth muscles
ANS responses in the heart are mediated primarily by
M2 and beta1
In most other tissues besides the heart, the dominant receptors are?
M3, beta2, or alpha1
The Gs-coupled beta receptors in the heart cause
increase in HR (chronotropic response) and an increase in the force of contraction/SV (inotropic response)
Chronotropic effects occur where?
on sinoatrial node cells
Inotropic effects stem from action on
regular cardiomyocytes
force of contraction
inotropic
rate of contraction and SA node cells
chronotropic
PANS receptors in the lung are primarily
M3 (although some autoinhibitor/presynaptic M2’s)
Activation of M3 receptors in the lung causes
bronchoconstriction and release of mucous
SANS receptors in the lung are primarily
beta2
beta2 receptors in the lung are located on
smooth muscle cells
activation of beta2 receptors in the lung causes
muscle relaxation and bronchodilation
Apocrine sweat glands and erector muscle contain
alpha1 receptors
activation of alpha1 receptors in apocrine sweat glands and erector muscle leads to
contraction of the glands (sweat production) and muscle (raised hair_
apocrine sweat glands are primarily located where?
in the armpits, genital area and palms of hands and feet
The sweating induced by NE/Ep is induced by what?
stress induced (not for thermoregulation)
The eccrine sweat glands express what type of receptor
primarily M3
Activation of the M3s on eccrine sweat glands does what?
contract the glands and induce sweating for the purpose of controlling body temperature
The detrusor muscle in the bladder contains which type of cholinergic receptors?
M3 receptors and to a lesser degree also M2 receptors
Activation of the M3 muscle in the bladder causes
contraction of the bladder wall and urge to urinate
the detrusor muscles primarily contain which type of adrenergic receptors
beta3 receptors
activation of the beta3 receptors in the detrusor muscle causes?
relaxes the bladder wall muscles
the muscles surrounding the urethra contain which type of adrenergic receptors
alpha1
activation of alpha1 receptors on the muscles surrounding the urethra causes
contraction of the urethra
the external urethral sphincter muscles contain which types of receptors
nicotinic cholinergic receptors innervated by the somatic nervous system
