Fundamental Notion Part 2 Flashcards
(34 cards)
What are receptors in the context of drug targets?
Receptors are proteins that recognize and respond to endogenous chemical messengers (such as hormones and neurotransmitters) and trigger a cellular response upon binding to specific ligands.
What is the difference between a full agonist and a partial agonist?
A full agonist binds to a receptor and produces the maximum possible response (highest Emax), while a partial agonist activates the receptor but produces a lower response than a full agonist (lower Emax).
What is an inverse agonist?
An inverse agonist binds to constitutively active receptors and produces the opposite effect of an agonist, reducing the receptor’s basal activity.
How do antagonists function?
Antagonists bind to receptors but do not elicit a biological response. Their effect is only observable in the presence of an agonist, as they block the receptor from being activated.
What are allosteric modulators?
Allosteric modulators are drugs that bind to a different site on a receptor than where the endogenous agonist binds, influencing the receptor’s function. Positive modulators enhance agonist effects, while negative modulators reduce them.
What is the function of ligand-gated ion channels?
Ligand-gated ion channels open and close in response to the binding of a chemical messenger (ligand), allowing the passage of ions across the cell membrane and facilitating rapid conversion of chemical signals into electrical signals.
Describe the mechanism of the nicotinic acetylcholine receptor (nAChR).
When acetylcholine binds to nAChR, the channel opens, allowing Na+ ions to enter the muscle cell, leading to depolarization and muscle contraction. Nicotine acts as a full agonist at this receptor.
What is the role of G-protein coupled receptors (GPCRs)?
GPCRs are membrane receptors that, upon ligand binding, activate intracellular signalling pathways through G proteins, leading to various biological effects via second messengers.
What are enzyme-linked receptors?
Enzyme-linked receptors are membrane proteins with enzymatic activity or associated with enzymes that become activated upon binding of an endogenous ligand, often involving phosphorylation processes.
How do nuclear receptors regulate gene expression?
Nuclear receptors bind to ligands (such as hormones), then translocate to the nucleus where they bind to DNA, regulating gene expression and subsequently impacting protein synthesis, with effects taking hours to manifest.
What is the role of the epidermal growth factor receptor (EGFR) in cancer treatment?
EGFR is a tyrosine kinase receptor often overexpressed in cancer. Drugs like Cetuximab target this receptor to inhibit cell growth and proliferation, acting as an anti-cancer therapy.
What is the difference between competitive and non-competitive antagonists?
Competitive antagonists bind to the same active site as the agonist and can be displaced by higher concentrations of agonist, while non-competitive antagonists bind to a different site and reduce the efficacy of the agonist regardless of its concentration.
What is the significance of constitutively active receptors?
Constitutively active receptors can have biological effects even in the absence of an agonist, contributing to baseline signalling and making them unique targets for inverse agonists.
How does phosphorylation affect receptor activity?
Phosphorylation, often facilitated by kinases in enzyme-linked receptors, can activate or deactivate receptors, altering their activity and impacting cellular responses.
How does the binding of a ligand to a GPCR initiate a signalling cascade?
Ligand binding to a GPCR causes a conformational change in the receptor, activating an associated G protein, which then triggers a cascade of intracellular events involving effector proteins and second messengers, leading to a biological response.
What types of molecules can serve as ligands for receptors?
Ligands can include hormones, neurotransmitters, ions, and various drugs that bind to receptors to elicit a biological response.
Why are allosteric modulators considered important in drug design?
Allosteric modulators provide an additional level of regulation, allowing for more nuanced control of receptor activity without directly competing with endogenous ligands, which can lead to fewer side effects.
What is the significance of the seven transmembrane helices in GPCRs?
The seven transmembrane helices are crucial for the structure and function of GPCRs, facilitating ligand binding and conformational changes that activate the G protein signalling pathway
How does nicotine act on the nicotinic acetylcholine receptor?
Nicotine acts as a full agonist on the nAChR, binding to the receptor and mimicking the action of acetylcholine, which leads to increased neuronal activity and can result in addiction.
What is the function of kinase-linked receptors?
Kinase-linked receptors have intrinsic enzymatic activity, often leading to phosphorylation of tyrosine residues on target proteins, which regulates various cellular functions including growth and differentiation.
How does the body’s response differ between agonists and antagonists?
Agonists activate receptors and mimic the action of natural ligands, producing a biological response, while antagonists block receptor activation, preventing the natural ligand from eliciting its effect.
What role do competitive reversible antagonists play in pharmacology?
Competitive reversible antagonists bind to the active site of receptors and can be displaced by higher concentrations of agonists, allowing for modulation of receptor activity based on ligand availability.
Why is the study of constitutively active receptors important for drug development?
Understanding constitutively active receptors can help in the development of inverse agonists that reduce unwanted baseline activity, providing therapeutic options for conditions related to overactive signalling.
What is the impact of ligand binding on nuclear receptors?
Ligand binding to nuclear receptors activates the receptor, allowing it to translocate to the nucleus, bind to DNA, and modulate gene expression, influencing long-term cellular functions.
