Lecture 2

What does the Law of Mass Action state?

The rate of a reaction is dependent on the concentration of the reagents (drug and receptor).

What is the Rate of Association?

How fast the drug and receptor bind.

What is the Rate of Dissociation?

How fast the drug and receptor unbind.

What is Equilibrium in the context of drug-receptor interactions?

Individual receptors can bind and unbind, but the net receptors are unchanged.

What does Kd represent?

The equilibrium dissociation constant; it is the rate of the dissociation constant (Koff) and the association constant (Kon) at equilibrium.

What does a low Kd value indicate about a drug's affinity?

Drugs with low Kd have a high affinity and bind well to receptors.

What does the Hill-Langmuir equation illustrate?

It shows a sigmoid curve indicating a maximum amount of receptors that can bind, and once that is reached, the maximum drug effect can no longer be increased.

What factors influence the sensitivity of a drug according to the Hill-Langmuir equation?

A drug with a higher affinity will need a lower concentration, shifting the curve to the left.

What defines the selectivity of drug effects?

The mutual affinity of a drug and its receptor, which is independent for each drug-receptor pair.

What are Receptors?

Proteins that respond to an external stimulus, causing a change inside the cell.

What is the function of Channels in cell membranes?

They form a pore for passive ion movement.

What do Transporters do?

They actively transport molecules independent of a concentration gradient.

What are Intracellular Receptors and how do they function?

They are inside cells and lipid soluble to cross the plasma membrane, commonly steroids that influence transcription of target genes.

How do G-protein coupled receptors (GPCRs) work?

Ligand binding causes a conformational change triggering interaction with nearby G proteins, activating a signal cascade.

What happens when a drug binds to GPCR?

It causes a conformational change in the GPCR, triggering interaction with a G protein inside the cell.

What do the G proteins do in signal transmission?

They bind GTP and GDP, and an activated GPCR causes GDP to swap for active GTP, dissociating the G protein into alpha and beta-gamma subunits.

What are the roles of the three G protein subunits: Gs, Gi, and Gq?

Gs stimulates the cell via adenylate cyclase; Gi inhibits the cell via adenylate cyclase; Gq modulates the cell via phospholipase C.

How do G beta-gamma subunits influence proteins?

G beta-gamma subunits can influence the activity of various proteins.

What triggers activation in Tyrosine Kinase Receptors?

Activation is caused by the dimerization of receptors when a ligand is present, which causes them to autophosphorylate.

What is the mechanism of Ion Channels?

They respond rapidly to electrical signals depending on stimuli such as ligand binding or voltage.

How do Active Transporters work?

They assist the movement of molecules against a concentration gradient across a membrane.

What effect does cocaine have on the dopamine transporter?

Cocaine blocks the dopamine transporter, leading to an accumulation of dopamine in the synapse.