Neurotransmission in Adrenergic Neurons
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Questions and Answers

What is the rate-limiting step in the formation of norepinephrine?

  • Decarboxylation of DOPA to dopamine
  • Hydroxylation of tyrosine to DOPA (correct)
  • Storage of dopamine in synaptic vesicles
  • Transport of tyrosine into the neuron

What happens to dopamine after its synthesis in the adrenergic neuron?

  • It is broken down into byproducts.
  • It is converted directly into norepinephrine.
  • It is released into the synaptic gap immediately.
  • It is transported into synaptic vesicles. (correct)

Which enzyme is responsible for converting tyrosine to DOPA?

  • Tyrosine hydroxylase (correct)
  • DOPA decarboxylase
  • Tyrosine decarboxylase
  • Aromatic l-amino acid decarboxylase

What is the role of reserpine in the context of adrenergic neurons?

<p>Blocks the amine transporter system for dopamine (A)</p> Signup and view all the answers

Which of the following steps is NOT involved in neurotransmission at adrenergic neurons?

<p>Elimination of electrical signals (B)</p> Signup and view all the answers

What percentage of norepinephrine is released by the adrenal medulla?

<p>20% (B)</p> Signup and view all the answers

What triggers the release of norepinephrine from neurons?

<p>An action potential arriving at the nerve junction (B)</p> Signup and view all the answers

What mechanism is utilized by norepinephrine to initiate intracellular events in the effector cell?

<p>Cyclic adenosine monophosphate (cAMP) second messenger system (C)</p> Signup and view all the answers

Which drug can inhibit the release process of norepinephrine?

<p>Guanethidine (C)</p> Signup and view all the answers

What happens to norepinephrine after it is released into the synaptic space?

<p>It diffuses out of the synaptic space and enters the general circulation (B)</p> Signup and view all the answers

What is the primary function of α2 receptors when stimulated?

<p>Inhibit the release of norepinephrine (D)</p> Signup and view all the answers

How do α2 receptors affect intracellular cAMP levels?

<p>Inhibit cAMP levels (B)</p> Signup and view all the answers

Which drug is a selective antagonist for α1A receptors?

<p>Tamsulosin (D)</p> Signup and view all the answers

What distinguishes β receptors from α receptors in their response to drugs?

<p>They respond strongly to isoproterenol with less sensitivity to epinephrine (D)</p> Signup and view all the answers

Which of the following α1 receptor subtypes is NOT part of the extended classification?

<p>α1Z (B)</p> Signup and view all the answers

What is the primary mechanism for the termination of norepinephrine's effects?

<p>Recapture by uptake system (A)</p> Signup and view all the answers

Which adrenergic receptor family shows a weak response to isoproterenol?

<p>Both α1 and α2-adrenoceptors (B)</p> Signup and view all the answers

What is the rank order of potency for α adrenoceptors?

<p>epinephrine &gt; norepinephrine &gt; isoproterenol (D)</p> Signup and view all the answers

What role does catechol-O-methyltransferase (COMT) play in norepinephrine metabolism?

<p>It converts norepinephrine into inactive metabolites (C)</p> Signup and view all the answers

Which substances can inhibit the uptake of norepinephrine?

<p>Cocaine and tricyclic antidepressants (C)</p> Signup and view all the answers

What effect is mediated by α1 adrenoceptors?

<p>Increased closure of internal sphincter of the bladder (C)</p> Signup and view all the answers

Which of the following effects is primarily associated with β2 adrenoceptors?

<p>Decreased peripheral resistance (A)</p> Signup and view all the answers

What is one mechanism suggested to explain receptor desensitization?

<p>Sequestration of receptors (D)</p> Signup and view all the answers

What is the potency rank order for β receptors?

<p>isoproterenol &gt; epinephrine &gt; norepinephrine (C)</p> Signup and view all the answers

What effect does β1 adrenoceptor activation primarily cause?

<p>Tachycardia (B)</p> Signup and view all the answers

Which of the following receptors primarily mediates responses in the heart?

<p>β1 receptors (A)</p> Signup and view all the answers

What is the primary effect of stimulating α1 receptors?

<p>Vasoconstriction in skin and abdominal viscera (D)</p> Signup and view all the answers

Which of the following does NOT describe the effects mediated by α2 adrenoceptors?

<p>Increased insulin release (C)</p> Signup and view all the answers

Which β receptor subtype has a higher affinity for epinephrine than norepinephrine?

<p>β2 receptors (B)</p> Signup and view all the answers

Which of the following statements about β3 receptors is true?

<p>They are involved in lipolysis. (C)</p> Signup and view all the answers

What structural feature of adrenergic drugs is crucial for their potency in activating receptors?

<p>Number and location of OH substitutions on the benzene ring (C)</p> Signup and view all the answers

Why are catecholamines ineffective when administered orally?

<p>They are rapidly metabolized by COMT and MAO in other tissues. (B)</p> Signup and view all the answers

Which of the following is NOT a characteristic of catecholamines?

<p>Long duration of action when given parenterally (D)</p> Signup and view all the answers

Which adrenergic drug is considered a catecholamine?

<p>Dopamine (A)</p> Signup and view all the answers

What is one of the common clinical effects of catecholamines on the CNS?

<p>Tremor (D)</p> Signup and view all the answers

What is a characteristic of noncatecholamines in comparison to catecholamines?

<p>They have longer half-lives due to lack of catechol hydroxyl groups. (A)</p> Signup and view all the answers

Which compound is an analog of epinephrine?

<p>Phenylephrine (B)</p> Signup and view all the answers

What effect does increased lipid solubility have on noncatecholamines?

<p>Increased access to the CNS. (A)</p> Signup and view all the answers

Which compound has an isopropyl substitution on the amine nitrogen?

<p>Isoproterenol (B)</p> Signup and view all the answers

How does the amine nitrogen substitution of epinephrine affect its potency?

<p>Increases potency at β receptors. (B)</p> Signup and view all the answers

Where are A-α1 receptors primarily located?

<p>On postsynaptic membranes of effector organs (D)</p> Signup and view all the answers

Which receptor has a greater affinity for phenylephrine compared to clonidine?

<p>α1 receptors (A)</p> Signup and view all the answers

What is produced as a result of phospholipase C activation by α1 receptors?

<p>Inositol-1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) (D)</p> Signup and view all the answers

Which type of adrenergic agonists act directly on α or β receptors?

<p>Direct-acting agonists (C)</p> Signup and view all the answers

What is the primary mechanism of action for indirect-acting agonists?

<p>Blocking the uptake of norepinephrine (D)</p> Signup and view all the answers

Which of the following is an example of a mixed-action agonist?

<p>Ephedrine (A)</p> Signup and view all the answers

Which of the following statements is true about direct-acting adrenergic agonists?

<p>They bind directly to adrenergic receptors. (D)</p> Signup and view all the answers

Which of the following drugs is classified as an indirect-acting agonist?

<p>Tyramine (B)</p> Signup and view all the answers

Flashcards

Norepinephrine Release Process

The process by which norepinephrine is released from nerve endings.

Norepinephrine Release Inhibition

Drugs like guanethidine can block the release of norepinephrine from nerve endings.

Norepinephrine Binding to Receptors

Norepinephrine binds to receptors on either the target cell or the nerve ending itself.

Norepinephrine Second Messenger Systems

Norepinephrine activates intracellular signaling through cAMP and phosphatidylinositol pathways.

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Norepinephrine Removal

Norepinephrine diffuses out of the synapse and into the bloodstream.

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What is the rate-limiting step in norepinephrine synthesis?

The conversion of tyrosine to DOPA by tyrosine hydroxylase is the rate-limiting step in the synthesis of norepinephrine. This means that the speed of this reaction determines the overall rate of norepinephrine production.

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How is dopamine transported into synaptic vesicles?

Dopamine is transported from the cytoplasm into synaptic vesicles by an amine transporter system. This carrier system is blocked by reserpine.

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What is the function of adrenergic neurons?

Adrenergic neurons are responsible for releasing norepinephrine, a neurotransmitter that plays a role in the sympathetic nervous system, regulating functions like heart rate, blood pressure, and fight-or-flight response.

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Where are adrenergic neurons located?

Adrenergic neurons are found in the central nervous system (CNS) and the sympathetic nervous system, acting as links between ganglia and effector organs.

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What is the purpose of norepinephrine removal from the synaptic gap?

Removal of norepinephrine from the synaptic gap is essential for regulating the duration and intensity of the signal. This process prevents overstimulation and ensures proper signal transmission.

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α2 Receptor Feedback Inhibition

Stimulating an α2 receptor on a sympathetic neuron reduces the release of norepinephrine from that neuron, acting as a negative feedback mechanism.

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α2 Receptor on Parasympathetic Neurons

Norepinephrine released from sympathetic neurons can bind to α2 receptors on presynaptic parasympathetic neurons, inhibiting the release of acetylcholine.

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α2 Receptor Signaling Pathway

Activation of α2 receptors leads to decreased cAMP production through inhibition of adenylyl cyclase.

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α1 Receptor Subtypes

α1 receptors are divided into α1A, α1B, α1C, and α1D. This distinction helps explain the selectivity of some drugs.

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β Receptors and Isoproterenol

β receptors respond strongly to isoproterenol, which is a more potent agonist than epinephrine and norepinephrine.

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α-Adrenoceptors

These receptors respond to natural catecholamines (epinephrine, norepinephrine) more strongly than synthetic agonists like isoproterenol. They are further divided into α1 and α2 subtypes based on their affinity for agonists and blocking drugs.

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Norepinephrine Metabolism - COMT

Catechol-O-methyltransferase (COMT) breaks down norepinephrine in the synaptic space, making it inactive.

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Norepinephrine Metabolism - Neuronal Uptake

Norepinephrine is reabsorbed back into the neuron by a sodium/potassium activated ATPase. Tricyclic antidepressants and cocaine can inhibit this process.

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Norepinephrine Metabolism - MAO

Monoamine oxidase (MAO) located in neuronal mitochondria oxidizes and inactivates norepinephrine.

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Norepinephrine Potency Order

The order of effectiveness for α receptors, from most to least potent: epinephrine > norepinephrine > isoproterenol.

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α1 Receptor Location

α1 receptors are mainly found on the postsynaptic membranes of effector organs, where they control smooth muscle contraction.

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α1 Receptor Activation

When α1 receptors are activated, they trigger a G protein-mediated pathway that leads to the production of IP3 and DAG. This results in the release of calcium from the endoplasmic reticulum and the activation of other cellular proteins.

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α2 Receptor Location

α2 receptors are predominantly located on presynaptic nerve endings, as well as in cells like pancreatic β cells and some vascular smooth muscle cells.

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α2 Receptor Function

α2 receptors play a role in regulating the release of neuromediators and insulin. They are also involved in controlling blood vessel constriction.

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Phenylephrine vs. Clonidine

Phenylephrine has a stronger affinity for α1 receptors compared to α2 receptors. Clonidine, on the other hand, prefers α2 receptors and has a weaker effect on α1 receptors.

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α1 Adrenoceptor Effect

α1 adrenoceptors cause vasoconstriction, increased peripheral resistance, increased blood pressure, bladder sphincter closure, and pupil dilation (mydriasis).

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α2 Adrenoceptor Effect

α2 adrenoceptors inhibit norepinephrine release, acetylcholine release, and insulin release.

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β1 Adrenoceptor Effect

β1 adrenoceptors increase heart rate (tachycardia), fat breakdown (lipolysis), heart muscle contraction (contractility), and renin release.

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β2 Adrenoceptor Effect

β2 adrenoceptors cause vasodilation, decreased peripheral resistance, bronchodilation, glycogen breakdown in muscles and liver, glucagon release, and relaxed uterine muscles.

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Adrenergic Receptor Desensitization

Prolonged exposure to adrenaline-like substances can cause desensitization of adrenergic receptors, making them less responsive. This occurs through receptor sequestration, down-regulation, or inability to couple with the G protein.

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β Receptor Potency Order

The potency of β-adrenoceptor agonists decreases in this order: isoproterenol > epinephrine > norepinephrine. This means isoproterenol is the most potent, followed by epinephrine, and then norepinephrine.

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β1 Receptor Affinity

β1 receptors have similar affinity for epinephrine and norepinephrine. This means they respond equally well to both neurotransmitters.

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β2 Receptor Affinity

β2 receptors have a stronger affinity for epinephrine than for norepinephrine, meaning they respond more readily to epinephrine.

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Adrenergic Receptor Distribution

Different tissues and organs predominantly express specific types of adrenergic receptors. For example, the heart mainly contains β1 receptors, while blood vessels have both α1 and β2, but β2 is more prevalent.

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Catecholamines

Catecholamines are a group of sympathomimetic amines that include epinephrine, norepinephrine, isoproterenol, and dopamine. They share a 3,4-dihydroxybenzene group structure.

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Catecholamine Potency

Catecholamines, due to their 3,4-dihydroxybenzene structure, have high potency in activating α or β receptors, making them powerful stimulators of the sympathetic nervous system.

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Catecholamine Inactivation

Catecholamines are rapidly inactivated by enzymes like COMT and MAO, found in both the nervous system and other tissues like the gut and liver.

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Catecholamine CNS Penetration

Catecholamines are polar molecules, which makes them unable to easily cross the blood-brain barrier, limiting their direct effects on the central nervous system.

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Catecholamine Clinical Effects on CNS

Despite their poor penetration into the brain, catecholamines can still produce CNS effects like anxiety, tremor, and headaches, indicating some indirect action.

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What are direct-acting adrenergic agonists?

Drugs that directly activate α or β receptors, mimicking the effects of sympathetic nerve stimulation or epinephrine release.

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What are examples of direct-acting adrenergic agonists?

Examples include epinephrine, norepinephrine, isoproterenol, and phenylephrine.

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What are indirect-acting adrenergic agonists?

Drugs that increase norepinephrine release or block its reuptake, indirectly boosting their effects.

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What are examples of indirect-acting adrenergic agonists?

Examples include amphetamine, cocaine, and tyramine.

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What are mixed-action adrenergic agonists?

Drugs that act both directly on receptors and increase norepinephrine release.

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Noncatecholamine Half-life

Noncatecholamines have longer half-lives compared to catecholamines due to their resistance to inactivation by catechol-O-methyltransferase (COMT).

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Phenylephrine vs. Epinephrine

Phenylephrine is a structural analog of epinephrine, lacking the hydroxyl groups on the benzene ring but having a single hydroxyl at position 3. Ephedrine also lacks ring hydroxyls but possesses a methyl substitution at the α-carbon.

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Noncatecholamines and MAO

Noncatecholamines are poor substrates for monoamine oxidase (MAO), leading to their prolonged duration of action.

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Lipid Solubility of Noncatecholamines

Many noncatecholamines have increased lipid solubility, enabling them to cross the blood-brain barrier more easily and access the central nervous system (CNS).

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Amine Substituent & β-Selectivity

The substituent on the amine nitrogen of an adrenergic agonist influences its β-selectivity. For example, epinephrine with a methyl group is more potent at β receptors than norepinephrine with an unsubstituted amine.

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Study Notes

Adrenergic Agonists

  • These neurons are found in the CNS and also in the sympathetic nervous system, linking between ganglia and effector organs
  • The adrenergic neurons and receptors (presynaptically on the neuron or postsynaptically on the effector organ)
  • Neurotransmission at adrenergic neurons involves five steps: synthesis, storage, release, receptor binding, and removal of the neurotransmitter from the synaptic gap.

1-Synthesis of norepinephrine

  • Tyrosine is transported by a Na+-linked carrier into the axoplasm of the adrenergic neuron, where it is hydroxylated to dihydroxyphenylalanine (DOPA) by tyrosine hydroxylase.
  • This is the rate-limiting step in the formation of norepinephrine.
  • DOPA is then decarboxylated by the enzyme DOPA decarboxylase (aromatic l-amino acid decarboxylase) to form dopamine in the cytoplasm of the presynaptic neuron.

2-Storage of norepinephrine in vesicles

  • Dopamine is then transported into synaptic vesicles by an amine transporter system. This carrier system is blocked by reserpine.

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Description

This quiz tests your knowledge on the key processes involved in neurotransmission at adrenergic neurons, including the synthesis and release of norepinephrine. Questions cover the roles of various enzymes and receptors, as well as drug interactions. Challenge your understanding of adrenergic signaling mechanisms!

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