ANS Pharmacology Flashcards
Major NT of parasympathetic nervous system
ACh
ACh binds what types of receptors?
Nicotinic (nAChR) = ionotropic
Muscarinic (mAChR) = metabotropic
Major NT of sympathetic nervous system
Norepinephrine (NE)
Synthesis of epinephrine only occurs where?
Adrenal medulla
[and in a few epinephrine containing neuronal pathways in brainstem]
What causes catecholamine (Epi and NE) release from the adrenal medulla?
Depolarization of preganglionic sympathetic neuron releases ACh, which binds nAChRs on adrenal medulla, causing release of catecholamines
Precursor to NE and Epi
Dopamine
Synthesis of ACh:
The choline transporter transports choline from the extracellular space into neurons and is dependent on extracellular ___ concentrations (needed for cotransport)
______ catalyzes the final step in the synthesis of ACh, which is then immediately sequestered within synaptic vesicles
Na+
Choline acetyltransferase (ChAT)
The _____-dependent ACh vesicular transporter is what transports ACh into neuronal vesicles
____ influx is what eventually promotes fusion of the vesicular and cell membranes, resulting in ACh release. The _____ protein complex is responsible for this fusion.
ATPase
Ca++; SNARE
Termination of acetylcholine signaling is done by acetylcholinesterase, which cleaves ACh into _____ and ______.
What is the fate of these two products?
Acetate — diffuses out of synapse
Choline — recycled into nerve terminal by choline transporter
Where are nicotinic vs. muscarinic ACh receptors found?
nAChRs are found in all ganglia (sympathetic and parasympathetic) and the adrenal medulla
mAChRs are found in smooth and cardiac muscle, gland cells, and nerve terminals (sympathetic and parasympathetic)
nAChRs are ligand-gated ion channels that allow ____ to pass through when activated. They are activated by both ACh and ______
Na+; nicotine
Predominant NT of the mammalian extrapyramidal system and of several mesocortical and mesolimbic neuronal pathways
Dopamine (DA)
Precursor to all catecholamines
Tyrosine
Synthesis of catecholamines and location of the steps
In the cytoplasm: Tyrosine —> Dopa —> Dopamine
In a vesicle: Dopamine —> NE —> Epi
For the storage of catecholamines, ______ transports DA into the vesicle during de novo synthesis. This transporter is relatively promiscuous and transports DA, NE, Epi, and serotonin across the vesicle membrane
VMAT2 (vesicular monoamine transporter)
The triggering event in the adrenal medulla for release of catecholamines is the release of ACh by a preganglionic fiber and its interaction with nAChRs on ____ cells to produce a localized depolarization
Chromaffin
What type of receptors are alpha and beta catecholamine receptors?
GPCRs
Methods of termination of catecholamine signaling
Reuptake
Dilution by diffusion
Metabolic transformation
Reuptake of catecholamines occurs by what 2 neuronal membrane transporters? What happens after reuptake?
NET - norepinephrine transporter
DAT - dopamine transporter
After reuptake, catecholamines are stored in vesicles by VMAT-2
Catecholamine signal termination by dilution/diffusion out of junctional cleft involves uptake at extraneuronal sites by the transporters ___, ___, and ____
ENT, OCT1, OCT2
Termination oc catecholamine signaling by metabolic transformation occurs by what 2 enzymes?
MAO — metabolizes catecholamines that have been released and undergone reuptake within the nerve terminal; associated with outer surface of mitochondria
COMT — major role in the liver; largely cytoplasmic
End result of adrenergic alpha-1 receptor activation
Muscle contraction
[vasoconstriction, glandular secretion]
End result of adrenergic alpha-2 receptor activation
Vascular smooth muscle contraction
Decreased insulin secretion
Decreased release of NE
Activation of any of the ____ catecholamine receptors results in activation of adenylyl cyclase and increased concentrations of cAMP through the stimulatory Gs protein
Beta
End result of adrenergic beta-1 receptor activation, which are mainly found in myocardium
Increased force and rate of heart contraction and AV nodal conduction velocity
End result of adrenergic beta-2 receptor activation, which are found on smooth muscle and most other sites
Vascular, bronchial, GU, and GI smooth muscle relaxation
End result of adrenergic beta-3 receptor activation, which are found only in adipose tissue
Lipolysis
Dopamine receptors are what type of receptors?
GPCRs
Result of stimulation of D1 receptors
Vasodilation
Natriuresis
Diuresis
Agonists of alpha1 receptors
Epi>NE
Agonists at alpha2 receptors
Epi>NE
Agonists at beta1 receptors
Epi=NE
Agonists at beta2 receptors
Epi»NE
Agonists at beta3 receptors
NE>Epi
In response to a variety of stimuli, such as ACh, vasoactive products like bradykinin, or physical stimuli, blood vessel endothelial cells release a short-lived vasodilator called _________, which is now known as NO
Endothelium-derived relaxing factor (EDRF)
Effects of EDRF release
EDRF release leads to ACh release, which activates mAChR on endothelial cells, leading to their dilation
Parasympathetic cholinergic effects
Salivation Lacrimation Pupil constriction Decrease HR Urination Increased secretions Increased GI motility
Sympathetic (adrenergic) effects
Pupil dilation Increased HR Urinary retention Decreased secretions Decreased GI motility
