Introduction to the ANS Flashcards
What are drug targets?
Receptors Proteins Hormone receptors Growth factor receptors Transcription factor receptors Neurotransmitter receptors Ion channels Enzymes Transport proteins Glycoproteins Structural proteins DNA
What are the types of receptor modulators?
Full agonist- complete mimicry
Partial agonist- only partial
Neutral antagonist
Inverse agonist (also called antagonist) - block constitutive activity.
Responses of effector organs to ANS impulses
see slide 7, table in DSA also, be familiar with table.
What is the sym receptor in the heart?
B1 mainly but also B2
What is the parasym receptor in the heart?
M2 mainly but also M3
What is the parasym neurotransmittor?
receptors?
Ach
nAChR, mAChR
What is the sym neurotransmittor?
receptors?
NE, Epi (DA) Ach/
alpha, beta (D), nAChR, mAChR
All preganglionic autonomic fibers are what type?
Cholenergic
What is cholinergic transmission?
a) Cholinergic neurotransmission refers to any neurotransmission in which ACh is released in vesicles; neurons that release ACh are called cholinergic neurons
Where are NNAChR found?
Where are mAChR found?
Within the ANS, NNAChRs are found in all ganglia (sympathetic and parasympathetic) and the adrenal medulla (sympathetic) while mAChRs are found in smooth and cardiac muscle, gland cells, and nerve terminals (sympathetic and parasympathetic)
What is adrenergic neurotransmission?
Adrenergic neurotransmission refers to neurotransmission in which catecholamines (NE, Epi, and DA) are released upon stimulation by an action potential (neurons that release catecholamines are called adrenergic neurons)
What are the catecholemines that we learned?
Precursor?
Norepinephrine, epinephrine (both adrenergic) and Dopamine (precursor to previous 2)
Tyrosine is precursor to all
What is the major NT of the Sym nervous system
Norepinephrine ( vast majority of postganglionic sym fibers)
Where does dopamine act?
CNS and renal vascular smooth muscle.
Talk about Cholinergic NT.
Axonal conduction
Junctional transmission (cholinergic) Synthesis of acetylcholine (ACh) Storage of ACh Release of ACh Destruction of ACh
ACh signaling
End organ effects
Describe nAChR?
Located in the CNS/Autonomic ganglia(Nn) (para) and adrenal medula (sym)
Excitatory (para) and release of catecholamines (sym)
Agonists- Ach and nicotine
Describe mAChR?
Located in CNS/autonomic ganglia; effector organs (cardiac and smooth muscle, gland cells, nerve terminals) (para)
Sweat glands ( sym)
Excitatory and inhibitory (para); sweat secretion (sym)
Agonists- Ach and muscarine.
Focus on M2 and M3
Slide 13
What are the two types of Ion channels?
What are the different drugs that inhibit
Voltage gated- local anesthetics
Ligand gated- neurotransmittor blockers
What are the steps in adrenergic neurotransmission?
Axonal conduction
Junctional transmission (adrenergic) Synthesis of catecholamines Storage Release Destruction (reuptake)
ACh signaling
End organ effects
Tyrosine> DOPA> Dopamine> NE> EPI; where do these occur?
First 2 in nerve cytoplasm last 3 in vesicle (last 2 mainly in adrenal medulla)
What are the transporters of adrenergic transmission?
What do they do?
Na+-dependent tyrosine transporter
Transports tyrosine into the nerve terminal
Vesicular monoamine transporter (VMAT-2)
Transports NE, Epi, DA, and serotonin into vesicles (promiscuous)
Release upon action potential and Ca2+ influx
NE transporter (NET) Imports NE into the nerve terminal Dopamine uptake occurs via a separate transporter (DAT)
What is the mechanism of re uptake?
Major mechanism that terminates the actions of catecholamines
NET (norepinephrine transporter) and DAT (dopamine transporter)
After reuptake, catecholamines are stored in vesicles by the VMAT-2
Focus on A1,2 and B1,2
Slide 22
All adrenergic receptors are metabotropic, what does this mean?
They are all G proteins.
Alpha 1 receptors (rule of thumb)
Stimulate contraction of all smooth muscle
Vascular smooth muscle – vasoconstriction
Beta 2 receptors?
Relax smooth muscle vasodilation.
Muscarinic receptors?
Contract smooth muscle (different intracellular signal than α1 receptors)
Apparent discrepancy – ACh & muscarinic agonists given IV cause vasodilation due to release of nitric oxide (NO)
What is the response of blood vessels to ANS impulses?
Adrenergic receptors in blood vessels receive sympathetic innervation, which cause vessel constriction (alpha1 receptors) or dilation (beta2 receptors) when activated
Smooth muscle of blood vessels is NOT innervated by parasympathetic neurons
AChRs (muscarinic and nicotonic) are not readily found on smooth muscle of blood vessels; but endothelial cells express mAChRs
Blood vessels relax in response to parasympathetic release of ACh as long as the endothelium is intact
How does EDRF promote vasodilation?
Activation of mAChRs on endothelial cells causes production and release of endothelium-derived relaxing factor (EDRF), aka nitric oxide (NO)
What are the effects of sym innervation of the adrenal medulla?
Epi and NE release is triggered by the release of ACh from the preganglionic fibers
ACh binds to NNAChRs and produce a localized depolarization
Release is approximately:
80% Epi
20% NE
What methods of intervention would these agents have? Examples. Choinomimetic agents Cholinoceptor-blocking drugs Sympathomimetic agents Adrenoceptor-blocking drugs
Cholinomimetic agents: drugs that mimic ACh
AChR agonists
Acetylcholinesterase inhibitors
Cholinoceptor-blocking drugs
AChR antagonists
Sympathomimetic agents: drugs that mimic or enhance α- and/or β-receptor stimulation
Agonists
Drugs that enhance catecholamine release
Drugs that block reuptake
Adrenoceptor-blocking drugs
α- and β-receptor antagonists
