Pharmacology Chapter on Receptors and Endocytosis

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Questions and Answers

What does endocytosis primarily involve?

Release of substances from the cell

Increase in the number of receptors

Uptake of molecules by cells (correct)

Modification of receptor proteins

What is indicated by the up regulation of receptors?

Decrease in receptor availability

Increase in receptor sensitivity (correct)

Change in receptor structure

Diminished cell response to stimuli

How can the affinity of an agonist be altered?

By modifying receptor structure (correct)

By increasing the concentration of antagonists

By decreasing receptor numbers

By inducing receptor degradation

What is a potential effect of active endocytosis in cells?

Altered receptor signaling Signup and view all the answers

Which best describes the concept of up regulation in pharmacology?

Increased receptor expression Signup and view all the answers

What is the term used for receptor mutations that lead to activation without the presence of a ligand?

Constitutive activation Signup and view all the answers

Which of the following is NOT a cause of receptor mutations leading to constitutive activation?

Environmental factors Signup and view all the answers

How can receptor mutations that cause constitutive activation occur?

Spontaneously, in disease, or experimentally Signup and view all the answers

What is a potential consequence of receptor mutations that lead to constitutive activation?

Unregulated cellular responses Signup and view all the answers

Which statement about receptor mutations is true?

They can cause abnormal receptor activation without any ligand present. Signup and view all the answers

What are the components of a G protein?

Alpha, beta, and gamma Signup and view all the answers

What can cause receptors to be activated without any external stimulation?

Receptor mutation Signup and view all the answers

In its normal resting state, what is the guanine nucleotide associated with the alpha subunit of the G protein?

GDP (guanosine diphosphate) Signup and view all the answers

What is a potential consequence of spontaneous receptor activation due to a mutation?

Uncontrollable severe muscle contraction Signup and view all the answers

Which of the following receptor types does the single chain amino acid receptor belong to?

G protein coupled receptor Signup and view all the answers

What role does the G protein play when the receptor is activated?

It undergoes a conformational change. Signup and view all the answers

Which condition exemplifies the issues caused by receptor mutation in the brain?

Epilepsy Signup and view all the answers

What primarily triggers uncontrollable stimulation in patients with epilepsy?

Recurrent receptor activation without stimulation Signup and view all the answers

What is the primary function of G protein coupled receptors?

Transmitting signals from outside the cell to inside Signup and view all the answers

What condition can lead to receptor mutation and consequent issues in the brain?

Exposure to chemicals Signup and view all the answers

What effect does creating an electrical charge change have on a cell?

It stimulates the cell for nerve signals or muscle contraction. Signup and view all the answers

Which process is NOT directly influenced by electrical charge changes in cells?

Transport of oxygen in the blood. Signup and view all the answers

How does electrical charge change impact muscle cells specifically?

It stimulates the muscle cells to contract. Signup and view all the answers

What is a potential consequence of insufficient electrical charge changes in nerve cells?

Delayed or impaired transmission of nerve signals. Signup and view all the answers

Which of the following accurately describes the relationship between electrical charge changes and cellular function?

Nerve and muscle cells specifically require electrical changes for functional signaling and contraction. Signup and view all the answers

What does Phospholipase C do in the context of G-proteins?

It acts as a catalyst to initiate a signaling process. Signup and view all the answers

Which G-protein class is NOT mentioned in the content?

Gt Signup and view all the answers

In terms of G-protein classes, which class is associated with stimulating adenylate cyclase?

Gs Signup and view all the answers

What role do G-proteins play in cellular signaling?

They act as molecular switches in signal transduction. Signup and view all the answers

Which statement correctly describes the relationship between Phospholipase C and G-proteins?

Phospholipase C is activated by G-proteins. Signup and view all the answers

Study Notes

Pharmacology II Lecture Notes

Course Details: Pharmacodynamics II, 2024-2025 academic year
Lecturer: Dr. Shereen Refaie
Date: November 2, 2023
Objectives: Students should be able to describe the two-state receptor model, identify four types of drug receptors and their signal transduction mechanisms, detail the structure and pathway of G-protein coupled, tyrosine kinase, and nuclear receptors, and explain mechanisms controlling receptor density at the cell membrane.

The Two-State Receptor Model

Receptors exist in two states: resting (R) and activated (R*).
These states are in equilibrium.
In the absence of a ligand, the equilibrium favors the resting state (R).
Ligands (drugs, hormones, or enzymes) shift the equilibrium towards the activated state.

Agonists and Equilibrium

Agonists bind to the resting state (R) and move the equilibrium towards the activated state (R*).
This binding leads to a cellular response.

Constitutive Receptor Activation

Receptors may be activated even without a ligand.
This can be due to spontaneous mutations or disease states.
This is termed "constitutive activation."

Inverse Agonists

Inverse agonists bind to the activated state (R*) and shift the equilibrium to the resting state.
This reduces receptor activity.

Receptor Types

Type 1: Ligand-gated ion channels (ionotropic receptors) - fast neurotransmitters.
Type 2: G-protein coupled receptors (GPCRs)
Type 3: Tyrosine kinase receptors; important receptors for example insulin receptors.
Type 4: Nuclear receptors - gene transcription.

G-Protein Signalling Mechanism

Step 1: Ligand binds to the receptor.
Step 2: Binding site fits ligand closely.
Step 3: Receptor conformation change/Alpha subunit of the G-protein loses GDP.
Step 4: GTP binds to the alpha subunit, causing it to detach from the beta/gamma subunits and the receptor.
Step 5: Alpha subunit attaches to adenylate cyclase.
Step 6: Activated alpha subunit activates adenylate cyclase.
Step 7: Adenylate cyclase converts ATP to cAMP.

Tyrosine Kinase Receptors

Extracellular: Drug binding site.
Intracellular: Tyrosine kinase enzymes.
Transmembrane: Connects the two parts.
Two receptors merge -> phosphorylation of intracellular parts.

Nuclear Receptors

Located inside the cell (cytoplasm or nucleus).
Ligands are highly lipid-soluble, allowing them to pass through the cell membrane.
Binding of ligands to receptors triggers gene activity -> delayed effects.
Example: Steroid hormones (corticosteroids, sex hormones).

Desensitization and Tachyphylaxis

Gradual decrease in drug response with repeated administration.
Characterized by reduced receptor activity.
Causes can include changes in receptors, mediator exhaustion, or increased metabolic degradation of the drug.

Tolerance

Gradual decrease in responsiveness to a drug over days or weeks.
Often associated with chronic drug use.

Control of Receptor Expression

Up-regulation: Increase in receptor expression due to continuous inhibition.
Down-regulation: Decrease in receptor expression due to continuous stimulation.

Quiz Questions and Answers

(See pages 32-35 for specifics.)

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Description

This quiz delves into essential concepts in pharmacology, focusing on endocytosis and receptor dynamics. It covers receptor mutations, agonist affinity alteration, and the implications of receptor behavior within cellular processes. Test your understanding of these critical topics in pharmacology and their cellular effects.