Pharma - Berto - L2 part 2

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Questions and Answers

What is a characteristic feature of ionotropic receptors?

They form a channel through the membrane. (correct)

They have tyrosine kinase activity.

They consist of a single subunit with 7 transmembrane domains.

They interact directly with the DNA in the nucleus.

Which type of receptor is associated with the fastest response time?

Tyrosine kinase receptors

Ionotropic receptors (correct)

Intracellular receptors

Metabotropic receptors

Which of the following neurotransmitters can activate both ionotropic and metabotropic receptors?

Noradrenaline

GABA

Glutamate (correct)

Serotonin

What is the primary property that allows a signal molecule to interact with intracellular receptors?

Lipophilicity Signup and view all the answers

How many subunits do metabotropic receptors typically have?

1 subunit with 7 transmembrane domains Signup and view all the answers

What type of receptors do noradrenaline and adrenaline exclusively interact with?

Metabotropic receptors only Signup and view all the answers

Which receptor type generally requires the longest time to trigger a response?

Intracellular receptors Signup and view all the answers

What is the main classification criterion for receptors?

Localization in the cell Signup and view all the answers

In which way can SERM influence estrogen receptors?

They can behave as either agonists or antagonists depending on the context. Signup and view all the answers

What role does Genistein play in biological systems?

It mimics the action of sexual hormones and acts as an endocrine disruptor. Signup and view all the answers

What are G-protein coupled receptors known for regarding their interaction with other receptors?

They can share intracellular pathways with tyrosine kinase receptors. Signup and view all the answers

What does the interaction termed 'cross-talk' refer to in receptor signaling?

The way different receptors regulate each other's pathways. Signup and view all the answers

What role do SSRIs play in pharmacology?

They inhibit the transport of monoamines, influencing serotonin levels. Signup and view all the answers

What is the primary function of phospholipase C in cellular signaling?

Conversion of PIP2 into IP3 and DAG Signup and view all the answers

How do ionotropic receptors differ from metabotropic receptors?

Ionotropic receptors directly open ion channels upon ligand binding. Signup and view all the answers

What is the significance of calcium ions in cellular processes?

Calcium ions act as important second messengers in various cellular processes. Signup and view all the answers

What characterizes a refractory state in ion channels?

The channel cannot be activated for a certain period after stimulation. Signup and view all the answers

What effect do benzodiazepines have on GABA A receptors?

They increase the opening frequency of channels in a GABA dependent manner. Signup and view all the answers

Which of the following is NOT a characteristic of ionotropic channels?

They are responsible for long-term cellular changes. Signup and view all the answers

What distinguishes mechanoreceptors from other ion channels?

They are activated by sensory stimuli. Signup and view all the answers

Which subtype of GABA receptors predominantly mediates inhibitory effects in the central nervous system?

GABA A receptors Signup and view all the answers

What is one of the roles of diacylglycerol (DAG) in cell signaling?

It recruits protein kinase C to the cellular membrane. Signup and view all the answers

What distinguishes metabotropic receptors from ionotropic receptors?

Metabotropic receptors have a single subunit with seven transmembrane domains. Signup and view all the answers

What is a primary role of the G-proteins' β and γ subunits?

To inhibit GDP dissociation from the heterotrimeric complex. Signup and view all the answers

Which G-protein is involved in the activation of phospholipase C?

Gq Signup and view all the answers

How do G-proteins contribute to signal transduction upon ligand binding?

They hydrolyze GTP to GDP, enabling effector interaction. Signup and view all the answers

What is the consequence of cholera toxin interacting with G-proteins?

It activates adenylyl cyclase continuously. Signup and view all the answers

What role do second messengers play in cellular signaling?

They are converted from ATP to cAMP by adenylyl cyclase. Signup and view all the answers

What effect does the enzyme phosphodiesterase (PDE) have on cAMP?

It converts cAMP into 5-AMP to inactivate it. Signup and view all the answers

What defines the fast kinetics of ionotropic receptors?

They cause immediate changes in membrane potential. Signup and view all the answers

Which statement is true regarding the role of RGS proteins?

They accelerate the deactivation of α subunits. Signup and view all the answers

In which context are mutations that constitutively activate G-proteins relevant?

They can lead to genetic diseases and tumor formation. Signup and view all the answers

What role does the magnesium ion play in NMDA receptor activation?

It blocks the conduction through the receptor. Signup and view all the answers

What characterizes AMPA receptors in terms of ion permeability?

Some variants can become permeable to calcium due to RNA editing. Signup and view all the answers

What distinguishes the flip and flop variants of GluR3 receptors?

Flop variants close their channels faster than flip variants. Signup and view all the answers

Which pathway is primarily associated with the activation of Receptor-Tyrosine Kinases (RTKs)?

Ras/Raf/MAPK pathway. Signup and view all the answers

What process occurs after RTKs are activated by ligand binding?

They autophosphorylate their tyrosine kinase domain. Signup and view all the answers

What is a key function of glycine receptors?

They regulate motor activity. Signup and view all the answers

How do estrogen receptors operate in a non-genomic way?

By activating other channels through phosphorylation. Signup and view all the answers

What is the main mediator of fast excitatory transmission among ionotropic glutamate receptors?

AMPA receptors. Signup and view all the answers

What is one of the key implications of long-term potentiation (LTP)?

It promotes synaptic plasticity and memory. Signup and view all the answers

What can trigger aberrant activation of receptor-tyrosine kinases potentially leading to cancer?

Mutations leading to receptor overactivity. Signup and view all the answers

Study Notes

Receptors Overview

Receptors are primary drug targets, influencing cell physiology through interaction with drugs.
They trigger transduction systems that lead to specific cellular responses.
Most drugs interact with receptors for endogenous mediators.

Classification of Receptors

Receptors are classified based on their localization:
- Membrane receptors (majority):
  - Ionotropic receptors: Form channels and act quickly (milliseconds).
  - Tyrosine kinase (TK) receptors: Characterized by tyrosine kinase activity, slower action.
  - Metabotropic receptors: G-protein-coupled, activate secondary messengers, slower response (seconds).
- Intracellular receptors: Respond to lipophilic signal molecules, slower action (hours), interact with DNA.

Neurotransmitter-Receptor Interaction

Neurotransmitters (NTs) can elicit rapid or slow responses depending on the receptor type:
- Acetylcholine:
  - Rapid response with nicotinic receptors (ionotropic).
  - Slower response with muscarinic receptors (metabotropic).
Other examples include GABA, glutamate, serotonin, and ATP with distinct receptor interactions.

Ionotropic vs Metabotropic Receptors

Ionotropic receptors:
- Comprise multiple subunits (4 or 5).
- Act without second messengers, lead to rapid ion flux.
Metabotropic receptors:
- Consist of a single subunit with 7 transmembrane domains.
- Activate second messengers for slower but prolonged actions.

G-Protein Coupled Receptors

Metabotropic receptors activate G-proteins with three subunits: α, β, and γ.
G-proteins have GTPase activity, hydrolyzing GTP to GDP, which activates effectors and second messengers.
Major G-protein families:
- Gs: Stimulates adenylyl cyclase (AC).
- Gi/Go: Inhibits AC.
- Gt: Important in vision.
- Gq: Activates phospholipase C (PLC).

G-Protein Activation Cycle

Unbound receptors do not interact with G-proteins.
Ligand binding causes a conformational change, activating G-proteins.
Activated α subunit interacts with effectors, while β and γ maintain receptor interaction and modulate activity.

Toxins and G-Protein Interaction

Cholera toxin: Constitutively activates Gs, leading to continuous AC activation.
Pertussis toxin: Inhibits Gi, blocking transduction.

G-Protein Effectors

Effectors are enzymes (e.g., AC, PLC) or ion channels that facilitate cellular responses.
Second messengers (e.g., cAMP, Ca²⁺) mediate intracellular signaling cascades.

Ion Channels

Ion channels can be voltage-gated or ligand-gated (e.g., ionotropic receptors).
Ionotropic channels:
- Feature rapid kinetics and provide selective ion conductance.
- Can lead to hyperpolarization or depolarization.

GABA A and Glycine Receptors

GABA A receptors: Main inhibitory ionotropic receptors, modulated by various drugs (e.g., benzodiazepines).
Glycine receptors: Similar to GABA A but with more limited distribution.

Ionotropic Glutamate Receptors

Types include AMPA and NMDA receptors, essential for excitatory neurotransmission.
AMPA receptors: Mediates fast transmission and can be modulated by RNA editing and alternative splicing.
NMDA receptors: Require both ligand binding and depolarization for activation due to magnesium blockade.

Receptor-Tyrosine Kinases (RTKs)

RTKs are key for cell signaling related to growth and differentiation.
Ligands include hormones and growth factors; dysfunctional RTK can lead to cancer.

Intracellular Receptors

Intracellular receptors, like those for sex hormones and glucocorticoids, act by diffusing across the membrane.
They may interact directly with DNA or carry out non-genomic actions, influencing multiple cellular pathways.

Summary

Understanding receptor types and their mechanisms is crucial in pharmacology and therapeutic development.
Targeting specific receptor pathways can provide insights into treating various diseases and conditions.### Estrogen Receptors and SERM
Selective Estrogen Receptor Modulators (SERM) can act as either agonists or antagonists.
The tissue type, binding site, and brain area determine the action of SERMs.
Estrogen receptors are classified into two types: α (alpha) and β (beta).

Ligand Interactions

Estrogen receptors have a broad binding site that allows interaction with various ligands.
Genistein, a natural ligand derived from soy, acts as an endocrine disruptor by mimicking sexual hormones.
Endocrine disruptors interfere with the normal development of organisms.

Receptor Interactions

Different receptors, like G-protein coupled receptors and tyrosine kinase receptors, can interact through shared intracellular pathways.
Types of interactions include:
- Convergence
- Divergence
- Amplification (cross-talk)
- Regulation (through cross-talk)

Drug Targets and Molecular Regulation

Drug targets extend beyond standard receptors to include those regulating molecular transport and membrane electrical activity.
Membrane transport systems, such as pumps and carriers, are crucial for pharmacological effects.
Selective Serotonin Reuptake Inhibitors (SSRIs) inhibit monoamine transport, highlighting their importance in pharmacology.

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Description

Explore the role of receptors in drug action and their classification. This quiz covers how drugs change cell physiology and interact with receptors on cell membranes or intracellularly. Test your knowledge on the different types of receptors and their functions.