Katzung - Chapter 9

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Questions and Answers

What is the primary neurotransmitter released by sympathetic nerve terminals?

Epinephrine

Serotonin

Dopamine

Norepinephrine (correct)

Which type of agonist directly stimulates adrenoceptors?

Enzyme inhibitors

Direct agonists (correct)

Reuptake inhibitors

Indirect agonists

What mechanism does tyramine utilize as an indirect agonist?

Displacing stored catecholamines (correct)

Preventing enzymatic degradation

Inhibiting reuptake

Blocking adrenoceptors

How does epinephrine function differently from norepinephrine?

Epinephrine acts as a hormone Signup and view all the answers

Which of the following is NOT a mechanism by which indirect agonists work?

Blocking receptor sites Signup and view all the answers

What role do G proteins play in the action of sympathomimetics?

They mediate signaling through adrenoceptors Signup and view all the answers

Which of the following agents inhibits the reuptake of norepinephrine?

Cocaine Signup and view all the answers

What distinguishes direct sympathomimetics from indirect sympathomimetics?

Direct sympathomimetics act on adrenoceptors directly Signup and view all the answers

What is a common effect of sympathetic stimulation via direct agonists?

Activation of adrenoceptors Signup and view all the answers

What effect do β antagonists have on aqueous humor?

They decrease its production. Signup and view all the answers

Which receptor subtype is likely involved in mediating constriction of the bladder base and prostate?

α1A receptors Signup and view all the answers

How does activation of β adrenoceptors in fat cells affect lipolysis?

It increases lipolysis and free fatty acid release. Signup and view all the answers

What role do α receptors play in urinary control?

They mediate contraction to promote urinary continence. Signup and view all the answers

What is a potential adverse effect of administering the α1 agonist midodrine?

Urinary retention. Signup and view all the answers

Which response is primarily mediated by β receptors in the liver after catecholamine release?

Enhanced glycogenolysis and glucose release. Signup and view all the answers

What effect does the binding of arrestin have on the receptor's capacity to activate G proteins?

It blunts the receptor's capacity. Signup and view all the answers

Which protein interacts with arrestin during the endocytosis of the receptor?

Clathrin Signup and view all the answers

What is the primary effect of blocking the norepinephrine transporter (NET)?

It increases synaptic norepinephrine levels. Signup and view all the answers

Which adrenoceptors are stimulated by the accumulation of cAMP due to β adrenoceptor activity?

Both α and β adrenoceptors Signup and view all the answers

What role does protein kinase A (PKA) play in receptor function when stimulated by β adrenoceptors?

Phosphorylates β receptors to inhibit function Signup and view all the answers

Where does phosphorylation of the β2 receptor occur?

on serine residues both in the third cytoplasmic loop and in the carboxyl terminal tail of the receptor. Signup and view all the answers

What is a possible consequence of activation of protein kinase C (PKC) in G protein-coupled receptors?

Phosphorylation that may inhibit receptor function Signup and view all the answers

Which transporters are involved in clearing dopamine, apart from the norepinephrine transporter (NET)?

Dopamine transporter (DAT) and serotonin transporter (SERT) Signup and view all the answers

What does receptor desensitization primarily achieve in signal transduction?

Prevention of overstimulation by agonists Signup and view all the answers

How does the transporter NET compare in affinity for dopamine versus norepinephrine?

Equivalent affinity for both Signup and view all the answers

What do D2 receptors inhibit?

Adenylyl cyclase activity Signup and view all the answers

What is selective receptor binding?

Binding preferentially to one receptor subgroup Signup and view all the answers

Which of the following statements about receptor selectivity is true?

Higher concentrations may cause interactions with additional receptor classes. Signup and view all the answers

What role do α-adrenoceptor subtypes play in physiology?

They play important roles in cardiac responses. Signup and view all the answers

What limitations exist in pharmacologic tools evaluating adrenoceptor function?

They have limitations related to specificity and selectivity. Signup and view all the answers

What is the significance of knockout mice in pharmacology?

They help in understanding receptor gene functions. Signup and view all the answers

Which statement accurately describes the concept of specificity in receptor selectivity?

Specificity entails preference without complete exclusion. Signup and view all the answers

What do the studies on knockout mice illustrate about receptor expression?

Receptor subtype expression varies by tissue type. Signup and view all the answers

What is primarily affected by the activation of Gq proteins in receptors?

Calcium influx Signup and view all the answers

The selective binding of drugs relates primarily to their effectiveness at which receptor types?

Major adrenergic receptor types Signup and view all the answers

What defines homologous desensitization in G protein-coupled receptors?

Loss of responsiveness exclusively in receptors exposed to an agonist. Signup and view all the answers

Which of the following is an example of heterologous desensitization?

Loss of function in β2 receptors without their direct activation. Signup and view all the answers

What is the role of G protein-coupled receptor kinases (GRK) in receptor desensitization?

They phosphorylate receptors, enhancing affinity for arrestins. Signup and view all the answers

Which agonist has the highest affinity for α1 receptors?

Phenylephrine Signup and view all the answers

In which situation does mixed receptor activation occur?

When multiple types of α and β receptors are activated simultaneously. Signup and view all the answers

Which of the following receptors is desensitized through homologous desensitization?

Only those that have been directly activated by an agonist. Signup and view all the answers

Which beta agonist shows the highest affinity for β1 receptors?

Dobutamine Signup and view all the answers

What effect does phosphorylation of agonist-occupied receptors have?

It enhances their affinity for arrestins. Signup and view all the answers

What receptor type does epinephrine have equal affinity for?

Both a1 and a2 and β1 and β2 receptors Signup and view all the answers

Which agonist has a greater affinity for β2 receptors compared to β1?

Albuterol Signup and view all the answers

Study Notes

Sympathomimetics Overview

Sympathomimetics are classified by mode of action and receptor activation spectrum.
Norepinephrine and epinephrine are direct agonists, activating adrenoceptors directly.
Indirect agonists enhance effects of endogenous catecholamines through different mechanisms.
Epinephrine is released from the adrenal medulla in response to stress; functions as a hormone, whereas norepinephrine is a neurotransmitter.

Mechanisms of Action

Indirect mechanisms include:
- Displacement of stored catecholamines (e.g., tyramine).
- Decreased clearance of norepinephrine through inhibition of reuptake (e.g., cocaine, tricyclic antidepressants).
- Inhibition of enzymatic metabolism (e.g., monoamine oxidase inhibitors).

G Protein-Coupled Receptors

G proteins consist of α, β, and γ subunits; classified by distinct α subunits.
D2 receptors can inhibit adenylyl cyclase, affect potassium channels, and decrease calcium influx.

Receptor Selectivity

Adrenergic agonists have selectivity for major receptor types: α1, α2, and β, not the subtypes within these groups.
Selectivity refers to a drug's preference for receptor subgroups, but not absolute; high concentrations may affect multiple receptors.
Knockout mice models help understand adrenoceptor subtype functions despite translational challenges to human physiology.

Desensitization Mechanisms

Homologous desensitization affects only receptors directly activated by agonists.
Heterologous desensitization involves interaction with unactivated receptors due to agonist exposure elsewhere.
Rapid desensitization involves phosphorylation of receptors by G protein-coupled receptor kinases.

Effects of α and β Agonists

Alpha Agonists:
- Phenylephrine and methoxamine predominantly activate α1 receptors.
- Clonidine and methylnorepinephrine predominantly activate α2 receptors.
Beta Agonists:
- Dobutamine primarily activates β1 receptors.
- Albuterol and metaproterenol primarily activate β2 receptors.
Norepinephrine equally activates α1 and α2, with higher activity on β1.

Clinical Implications

Activation of α receptors in genitourinary systems promotes muscle contraction for urinary continence.
β activation in fat cells increases lipolysis, promoting free fatty acid release.
Activation of D2 receptors in the kidney can enhance perfusion in low urine output scenarios.
Sympathomimetic drugs can lead to increased glycogenolysis in the liver, impacting blood glucose levels.

Potential Adverse Effects

Urinary retention can occur with α1 agonists, affecting bladder and prostate function.
High catecholamine concentrations may result in metabolic acidosis.

Summary of Physiological Functions

Different adrenoceptor subtypes have varied roles:
- α1A in bladder and prostate contraction.
- β receptors mainly mediate catecholamine effects in the liver.
The study of adrenoceptor functions is crucial for understanding drug mechanisms and developing therapeutic strategies.

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Description

Explore the fascinating world of sympathomimetics and their role in the autonomic nervous system. This quiz delves into their modes of action, receptor activation, and the physiological effects on blood pressure during stress. Test your understanding of these critical pharmacological agents.