Lecture 8: Catecholamines 2 Flashcards
What other catecholamine is norepinephrine similar too?
Dopamine
How are catecholamines are loaded into synaptic vesicles?
vesicular monoamine transporters (VMAT)
What psychostimulants cause release of catecholamines without nerve firing?
amphetamine and methamphetamine
What happens to catecholamines after release?
They are recycled by a process of reuptake
What happens in NE reuptake?
NE transporters return the transmitters to the releasing cell for breakdown or repackaging into vesicles.
What cells participate in uptake?
Postsynaptic cell or glial cells by non-selective transporters.
What do transporter-blocking drugs do for DA or NE?
Enhance transmission by increasing the amount of neurotransmitter available.
What does Ritalin do?
Ritalin blocks the norepinephrine transporter (NET), which normally reabsorbs NE from the synaptic cleft.
What happens to the extracellular levels of NE with Ritalin?
Leads to higher levels of extracellular NE, enhancing adrenergic signaling.
What are symptoms of increased NE?
Increased alertness, attention, and reaction speed.
What part of the brain is crucial for focus, impulse control, and working memory?
The prefrontal cortex
What does increasing NE (and DA) levels in the PFC do?
Ritalin helps ADHD patients sustain attention and regulate emotions.
What is propranolol and what does it do?
β-antagonist; treats hypertension by blocking β-receptors in the heart, reducing its contractile force
Identify medical conditions or disorders that can be treated with peripherally acting noradrenergic drugs, and name the drugs used for these disorders.
What is the organization of the noradrenergic system.
What is the function of the noradrenergic system.
Identify the primary source of forebrain NE.
What are the main target areas innervated by noradrenergic fibers?
What are the physiological effects of peripheral NE originating in the sympathetic nervous system and the adrenal glands?
List the adrenergic receptor subtypes.
What are adrenergic receptor subtypes respective signaling mechanisms?
Explain the mechanisms by which the noradrenergic system helps regulate anxiety.
Explain the mechanisms by which the noradrenergic system helps regulate arousal.
Explain the mechanisms by which the noradrenergic system helps regulate cognition.
Explain the mechanisms by which the noradrenergic system helps regulate the consolidation of emotional memories.
Identify medical conditions or disorders that can be treated with peripherally acting noradrenergic drugs.
Name the drugs used for treating symptoms with noradrenergic drugs.
How is Ritalin unlike amphetamines?
Ritalin does not trigger the direct release of NE from nerve terminals. Prolongs the action of naturally released NE by preventing its reuptake. This makes its effects more controlled and less likely to cause overstimulation compared to amphetamines.
What degrades the NE that diffuses out of the synapse inside the neuron?
Monoamine Oxidase (MAO)
What degrades the NE that diffuses out of the synapse in the synaptic cleft and surrounding tissues?
Catechol-O-Methyltransferase (COMT)
Where is norepinephrine an important transmitter?
In both the central and peripheral nervous systems
Where are NE neurons in the brain located?
In the pons and medulla, especially in the locus coeruleus (LC)
What do all neurons in the LC do?
Express the enzyme DBH and synthesize NE
Where does the LC send fibers?
To almost all areas of the forebrain – many involved in sensory information processing, also to the cerebellum and spinal cord.
About how many receptors in humans are for norepinephrine?
~50,000 out of ~86 billion!
What else to the fibers from the LC do?
extends to nearly all the forebrain, provides almost all NE input to cortex, limbic system, thalamus and hypothalamus (also to spinal cord and cerebellum)
What is Dexmedetomidine (Precedex)?
α2-agonist with combined sedative, anxiolytic, and analgesic effects
What is Isoproterenol (Isuprel)?
β-receptor agonist; treats bradycardia
What is Yohimbine (Yocon)?
α2-antagonist; treats male sexual impotence
What is Prazosin (Minipress)?
α1-antagonist; treats hypertension by dilating blood vessels
What is the benefit of metoprolol (Lopressor) and other β1-selective antagonists?
fewer side effects
What are Midodrine (ProAmatine) and metaraminol (Aramine)?
α1-agonists; treat hypotension
What is Propranolol and other β-antagonists (beta blockers) also used to treat?
generalized anxiety disorder
What does NE released from the LC fibers do?
acts on adrenergic receptors located in the central nervous system or in peripheral target organs
Identify NE in the PNS.
neurons that have cell bodies in ganglia of the sympathetic nervous system use NE
What does NE function as? And what does that allow it to do?
a hormone secreted by the adrenal glands; thus NE can reach organs in two ways
How do two types of NE and one type of EPI work together?
Bloodborne NE and EPI work with NE released from sympathetic nerve endings to mediate the “fight-or-flight” response
How do norepinephrine and epinephrine act?
through α- and β-adrenergic receptors
What type of receptors are Adrenergic receptors (adrenoceptors)?
metabotropic
What do β1- and β2- receptors do?
stimulate adenylyl cyclase and enhance formation of cAMP.
What do α2-receptors do?
inhibit adenylylcyclase and reduce the rate of cAMP synthesis; also increase opening of K+ channels
What do α1 receptors use?
The phosphoinositide second-messenger system
What symptoms can α2-agonists such as clonidine (Catapres) and lofexidine (Lucemyra) treat?
symptoms of opioid withdrawal by stimulating α2-autoreceptors to inhibit noradrenergic cell firing
What does the α2-antagonist yohimbine do and what does it lead to?
Blocks the autoreceptors, increasing noradrenergic cell firing and NE release; provokes withdrawal symptoms and drug craving
What can NE promote?
feelings of anxiety: tested with human-sized elevated plus maze
What plays a significant role in arousal, cognition, and the consolidation of emotional memories?
The central noradrenergic
What mechanisms surround arousal?
Arousal: LC neurons fire more rapidly during waking than during sleep, and trigger arousal
What does the α1-receptor agonist phenylephrine do?
Injected into the lateral hypothalamic area increased awake time in rats.
What does the β-receptor agonist isoproterenol do on its own and with phenylephrine?
Had less effect; together they had an additive effect
What part of the brain does the LC also project to? What happens?
the PFC, which expresses α1-, α2-, and β-receptors; facilitates cognition
What does nn α2-receptor agonist such as clonidine or guanfacine do?
Enhances working memory; activation of α1-receptors (lower affinity) decreases cognitive functions
When does optimal cognitive function occur?
at moderate amounts of NE release
How does α1 activation differ from a2?
has deleterious effects on cognitive function
How can NE be regulated?
Receptor affinity; NE has lower affinity for α1 than α2
What leads to optimal working memory?
Non-stressful conditions, activation of α2.
What happens in high stress?
α1 overrides the beneficial effects of α2
What is stress associated with?
one-trial passive avoidance learning produces increased EPI and glucocorticoid secretion from the adrenal glands plus activation of LC neurons and increased release of NE
What is a key brain structure that also plays a role in other types of fear conditioning.
basolateral amygdala (BLA)
How is Asthma and COPD treated in the PNS?
with β2-adrenoceptor agonists including albuterol (Ventolin) and levalbuterol (Xopenex)
What is an ingredient in OTC decongestant medications and what does it do?
The α1-receptor agonist phenylephrine– constricts blood vessels
What do α2-receptor agonists such as clonidine treat?
Hypertension by inhibiting the sympathetic nervous system while stimulating the parasympathetic system.
