Cell Bio Modern Receptor Theory

Week 3 sept 16

Affinity

The ability of a molecule (ligand) to bind to its receptor — “stickability.”

Efficacy

The ability of a molecule to produce a response after binding — “doability.”

Ligand

A molecule that binds to a receptor (e.g.

Receptor

A protein that binds specific ligands and triggers a cellular response.

Agonist

A molecule that binds to and activates a receptor to produce a biological effect.

Antagonist

A molecule that binds to a receptor but does not activate it — it blocks agonist action.

Competitive Antagonist

An antagonist that competes with the agonist for the same binding site; its effect can be overcome by increasing agonist concentration.

Noncompetitive Antagonist

An antagonist that binds irreversibly or to a different site; its effect cannot be overcome by increasing agonist concentration.

Partial Agonist

A ligand that binds to all receptors but only produces a partial response.

Full Agonist

A ligand that produces the maximum possible response when all receptors are occupied.

Inverse Agonist

A ligand that reduces constitutive receptor activity below basal levels.

Constitutive Activity

Receptor activity that occurs in the absence of any ligand.

Spare Receptors

When maximal response is achieved even though not all receptors are occupied.

Occupancy Model

The idea that the magnitude of response is proportional to the number of occupied receptors.

Law of Mass Action

The principle describing the equilibrium between bound and unbound receptors and ligands.

KD (Dissociation Constant)

The equilibrium constant for ligand–receptor binding; a lower KD means higher affinity.

EC50

The concentration of a drug that produces 50% of its maximal effect.

Potency

The amount of drug needed to produce a given effect; inversely related to EC50.

Efficacy (Emax)

The maximum response achievable by a drug.

Stochastic

Random or probabilistic — receptor binding occurs randomly.

Orthosteric Site

The primary (active) binding site on a receptor where the endogenous ligand binds.

Allosteric Site

A secondary binding site on a receptor that modulates the effect of the primary ligand.

PAM (Positive Allosteric Modulator)

A molecule that enhances the effect of an agonist at a receptor.

NAM (Negative Allosteric Modulator)

A molecule that decreases the effect of an agonist at a receptor.

Biased Agonism

When an agonist preferentially activates one signaling pathway over another through the same receptor.

Probe Dependence

When an allosteric modulator affects different agonists at the same receptor differently.

Intrinsic Activity

The property of a ligand describing its ability to activate a receptor after binding.

Induced Fit Model

Model where ligand binding causes a conformational change in the receptor.

Conformational Selection

Model where ligand stabilizes an already existing receptor conformation.

Conformational Change

A structural rearrangement in the receptor after ligand binding that alters function.

Physiological Antagonism

When two agonists acting on different receptors produce opposite effects.

Dose-Response Curve

A plot showing the relationship between drug concentration and response.

Hill-Langmuir Equation

Describes the relationship between ligand concentration and receptor occupancy.

Surmountable Antagonism

Antagonism that can be overcome by increasing agonist concentration.

Irreversible Antagonism

Antagonism that cannot be overcome by increasing agonist concentration.

Concentration-Response Relationship

Relationship between drug dose (concentration) and resulting biological effect.

Constitutive Receptor

Receptor that is active even in the absence of ligand binding.

Receptor Reserve

The proportion of receptors not needed for maximal response — same as spare receptors.

Allosteric Modulation

Regulation of receptor activity by binding of a molecule at a site distinct from the agonist site.

Emax

The maximum possible effect of a drug regardless of dose.

Potency Ratio

The comparison of two drugs’ EC50 values to measure relative potency.

Langmuir Isotherm

The model describing equilibrium between molecules binding to and leaving a surface — basis for receptor occupancy theory.

Intrinsic Efficacy

The ability of a ligand to stabilize an active conformation of a receptor.

Constitutive Receptor Activity

Receptor activity in the absence of any ligand — basal signaling.

Stochastic Binding

Random and reversible process of ligand–receptor interaction.

Positive Allosteric Modulation

Enhancement of agonist binding or effect by allosteric interaction.

Negative Allosteric Modulation

Reduction of agonist binding or effect by allosteric interaction.

Probe Dependence

“Texture” — when the same allosteric modulator affects different agonists differently.

Ceiling Effect

The maximum effect achievable with an allosteric modulator due to site saturation.

Spatial Selectivity

Allosteric modulator binds selectively to receptor subtypes in different regions.

Temporal Selectivity

Allosteric modulator acts only when the endogenous ligand is released. - describes how receptors, through various mechanisms, respond preferentially to certain timing characteristics of a stimulus, rather than just its presence or intensity