Fundamental Notion Part 2 Flashcards
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.
