Pharmacodynamics 1 final

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Questions and Answers

What structural feature do G protein-coupled receptors (GPCRs) possess?

Nine transmembrane helices

Eight transmembrane helices

Seven transmembrane helices (correct)

Five transmembrane helices

What occurs immediately after the binding of a ligand to a GPCR?

G protein inactivation

Receptor desensitization

Receptor activation (correct)

Effector protein activation

Which G protein subunit is responsible for promoting the exchange of GDP for GTP?

β subunit

α subunit (correct)

δ subunit

γ subunit

Which effector protein is activated by the GTP-bound α subunit of GPCR?

Adenylyl cyclase (B) Signup and view all the answers

What is a primary function of second messengers generated by GPCR activation?

Activate downstream signalling pathways (C) Signup and view all the answers

Which second messenger is specifically produced by adenylyl cyclase?

Cyclic adenosine monophosphate (cAMP) (D) Signup and view all the answers

What is the primary mechanism through which ligand-gated channels operate?

Conductance is regulated by ligand binding. (C) Signup and view all the answers

What role does cGMP play in cellular signaling?

Activates protein kinase G (A) Signup and view all the answers

Which of the following functions is NOT associated with ion channels?

Immune response (D) Signup and view all the answers

What is the first step in the mechanism of action for GPCRs?

Ligand binding (B) Signup and view all the answers

Which of the following results from the activation of protein kinase A (PKA)?

Alteration of target protein activity (B) Signup and view all the answers

Benzodiazepines primarily influence neuronal activity by enhancing which neurotransmitter's activity?

GABA (A) Signup and view all the answers

What occurs when local anesthetics block voltage-gated sodium channels?

Action potentials cannot be initiated or propagated. (D) Signup and view all the answers

What occurs to the G protein after the α subunit is activated?

The α subunit dissociates from βγ subunits (A) Signup and view all the answers

Second messenger-regulated channels are primarily activated by which of the following?

Binding of ligands to transmembrane receptors. (C) Signup and view all the answers

How do benzodiazepines alter the electrical state of neurons?

By enhancing chloride influx. (B) Signup and view all the answers

What is a key characteristic of the blockade caused by local anesthetics?

It is a reversible blockade. (A) Signup and view all the answers

Which ion is predominantly regulated by voltage-gated ion channels?

Sodium (A) Signup and view all the answers

What effect does the binding of catecholamines to beta-adrenergic receptors primarily have?

Activates G proteins and increases intracellular cAMP levels (C) Signup and view all the answers

What type of channel changes conductance in response to alterations in voltage across the plasma membrane?

Voltage-gated channels (B) Signup and view all the answers

Which of the following is NOT a major class of G protein isoforms?

Gx (C) Signup and view all the answers

Which mechanism describes the process by which local anesthetics prevent action potential propagation?

Blocking voltage-gated sodium channels. (A) Signup and view all the answers

Which mechanism is primarily used by receptors with linked enzymatic domains?

Addition or removal of phosphate groups (D) Signup and view all the answers

What is a primary function of the protein kinase C (PKC) pathway?

Regulate cell growth and differentiation (A) Signup and view all the answers

Which receptor is involved in the mobilization of energy from fat cells?

β3 receptor (C) Signup and view all the answers

Transmembrane receptors typically differ from GPCRs in what way?

They are single-membrane spanning proteins (D) Signup and view all the answers

What is the role of inositol trisphosphate (IP3) in cellular signaling?

Releases calcium from intracellular stores (B) Signup and view all the answers

Which of the following physiological processes is NOT mentioned as a role of transmembrane receptors?

Hormonal regulation (A) Signup and view all the answers

How do receptors with linked enzymatic domains transmit signals?

By converting ligand-binding to enzyme activity (D) Signup and view all the answers

What is a primary effect of vasodilation facilitated by certain signaling molecules?

Increased blood flow (C) Signup and view all the answers

What is the primary function of phosphorylated tyrosine residues on receptor tyrosine kinases (RTKs)?

They act as docking sites for various intracellular signaling proteins. (C) Signup and view all the answers

In the process of dimerization of receptor tyrosine kinases (RTKs), what is the first molecular event that occurs?

Binding of a specific ligand to the extracellular domain. (A) Signup and view all the answers

What role do receptor tyrosine kinases (RTKs) play in relation to cancer?

They can be mutated or dysregulated, leading to uncontrolled cell growth. (B) Signup and view all the answers

Which pathway is NOT typically associated with the signaling mechanisms activated by receptor tyrosine kinases (RTKs)?

Cyclic AMP (cAMP) pathway (C) Signup and view all the answers

Which statement best describes the structure of the insulin receptor?

Two membrane-spanning β subunits linked to two extracellular α subunits. (A) Signup and view all the answers

What immediate effect follows the binding of insulin to its receptor?

Dimerization and autophosphorylation of the receptor. (A) Signup and view all the answers

What cellular responses result from the activation of insulin receptor substrate (IRS) proteins?

Decreased lipolysis and enhanced glucose uptake. (A) Signup and view all the answers

Which process is primarily regulated by receptor tyrosine kinases (RTKs)?

Cell growth, differentiation, and metabolism. (D) Signup and view all the answers

What can defects in post-insulin receptor signaling lead to?

Type 2 diabetes mellitus in some cases. (B) Signup and view all the answers

Which statement accurately describes the autophosphorylation process in receptor tyrosine kinases?

It occurs after dimerization of the receptors on specific tyrosine residues. (B) Signup and view all the answers

Study Notes

Transmembrane Ion Channels

Many cellular processes need ions and hydrophilic molecules to pass through the plasma membrane
Specialized transmembrane channels regulate this ion transport
Ion channel functions include neurotransmission, cardiac conduction, muscle contraction, and secretion

Three Major Mechanisms of Transmembrane Ion Channels

Ligand-gated channels: Ion conductance is regulated by ligands binding to the channel (e.g., cholinergic nicotinic receptors)
Voltage-gated channels: Ion conductance is altered by changes in voltage across the plasma membrane (e.g., voltage-gated calcium channels)
Second messenger-regulated channels: Ligand binding to transmembrane receptors triggers second messenger generation, which then regulates ion channel conductance

Drugs Altering Ion Channel Conductance

Local anesthetics: Block voltage-gated sodium channels, preventing sodium influx and action potential propagation, thus inhibiting pain perception
Benzodiazepines: Bind to the GABA receptor complex, enhancing GABA's ability to open chloride channels increasing chloride influx, leading to hyperpolarization of the neuron and effects like sedation, anxiolysis, muscle relaxation, and anticonvulsant actions.

G Protein-Coupled Receptors (GPCRs)

GPCRs are the most abundant receptors in the human body, located on the plasma membrane's extracellular surface.
Structure: Seven transmembrane helices in a single polypeptide chain. The extracellular domain often contains the ligand-binding region. The intracellular part contains a G-protein (e.g., Gs, Gq, Gi) with three subunits (α, β, and γ)
Mechanism of Action (MOA):
- Ligand binding to the extracellular domain induces conformational changes in the GPCR
- This activates the associated G protein, causing GDP to be replaced with GTP on the α subunit
- The GTP-bound α subunit dissociates from the βγ subunits.
- The dissociated α subunit and βγ subunits interact with various effector proteins
- Effector proteins generate second messengers (e.g., cAMP, cGMP, IP3, DAG)
- Second messengers activate downstream signaling pathways

Intracellular Signaling through Second Messengers

cAMP: Activates protein kinase A (PKA); involved in phosphorylation of target proteins, metabolism regulation, and smooth muscle relaxation.
cGMP: Activates protein kinase G (PKG); facilitates smooth muscle relaxation and inhibits platelet aggregation.
IP3: Releases Ca²⁺ from intracellular stores, increasing cytosolic Ca²⁺ concentration, triggering downstream events like smooth muscle contraction.
DAG: Activates protein kinase C (PKC), regulating cell growth, differentiation, and smooth muscle contraction.

Major G Protein Families

Different G protein isoforms (types) with unique effects on targets; crucial for drug selectivity
Categorized into major families including Gs, Gi, Go, Gq, and G12/13 (see table)

Beta-Adrenergic Receptors

A significant class of GPCRs
Includes three subtypes (β1, β2, and β3)
Important in regulating heart rate, smooth muscle relaxation, and mobilization of energy from fat cells via cAMP signaling pathways

Transmembrane Receptors with Linked Enzymatic Domains

These receptors act as signal transducers, linking ligand binding to intracellular actions by activating a connected enzymatic domain—part of the receptor itself or a cytosolic protein.
This domain generally modifies proteins via phosphorylation or dephosphorylation, affecting cell function.

Receptor Tyrosine Kinases (RTKs)

Largest class of transmembrane receptors with cytoplasmic enzymatic domains
Transduce signals from hormones and growth factors by phosphorylating tyrosine residues on the intracellular part of the receptor.
Activation of downstream signaling pathways like MAPK, PI3K/Akt, PLCy pathways are possible through docking of signaling proteins and the phosphorylated tyrosines.
Key role in various cellular processes (growth, differentiation, survival, and metabolism)
Mutations or dysregulation can contribute to diseases, especially cancer.

Insulin Receptor (RTK example)

Structure: Composed of two extracellular α subunits and two transmembrane β subunits
Mechanism of Action: Insulin binding to the extracellular α subunits initiates receptor dimerization and autophosphorylation.
Following autophosphorylation, intracellular signaling proteins (e.g., IRS) are recruited, activating intracellular signaling pathways and leading to responses like glucose uptake, glycogen synthesis and glucose homeostasis.

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Description

This quiz explores the functionality and mechanisms of transmembrane ion channels, essential for various cellular processes. It covers ligand-gated, voltage-gated, and second messenger-regulated channels, as well as the impact of drugs on ion conductance. Test your understanding of these critical elements in cellular biology!