Pharmacodynamics - Part 3 Flashcards
What are two differnt chemical messengers?
NTs and hormones
Neurotransmitters
- ________ released from ______ endings which travel across a nerve _______ to bind with receptors on target cells, such as _____ cells or another _____.
- response is usually _____-lived and responsible for messages between ________ cells.
chemical nerve synapse muscle nerve short individual
Hormones:
- _______ released from ______ or ______ and which travel some _______ to bind with receptors on target cells _______ the body
chemicals
cells or glands
distance
throughout
Both NTs and hormones are ______ metabolites generated by ______ cells.
natural
living
Chemical messengers switch ___ receptors _______ undergoing a reaction.
on
without
Hormones can be made of what?
Lipids or peptides
i.e. precursors are lipid or protein based
NT precursor is what?
amino acids
One cell has many different ________.
receptors
Why is epinephrine also called adrenaline?
Synthesized from the adrenal glands - adrenaline
Generated from the glands atop kidneys - nephron - epinephrine
What are the major receptor classes?
Ion-channel receptors
GPCR
Kinase linked receptos
intracellular receptors
Which receptors are membrane bound?
Ion-channel
GPCR
kinase linked
Intracellular receptors are of two types, these are?
Nuclear receptors or ligand-activated TF
What is the response time of ion-channel receptors?
GPCR?
Kinase linked receptor?
msecs
seconds
minutes
What is the signal transduction step of ion-channel receptors?
activation of conductance
- change membrane permeability (potential)
What is the signal transduction step of GPCR?
genreation of secondary messenger –> activation of cell signaling
What is the signal transduction step of kinase linked receptor?
activation of cell signaling
What is the signal transduction step of intracellular receptor?
activation of transcriptoin and translation
Ion channel receptors:
- _____ response –> ___
- ideal for transmission between ______
- binding of messenger leads directly to ____ ______ across the cell memrbane
- secondary effect = ____ _____ (signal transduction)
- ion concentration within cell ______
- leads to variation in cell ______
fast - msec nerves ion flow ion flow alters chemistry
Ion channel receptors:
- cationic ion channels - _______
- anionic ion channels - _______
excitatory
inhibitory
Ion channel receptors are _______ in the membrane
embedded
How many subunits does an ion channel receptor have?
How many polypeptides?
5
5
How does the ion channel open?
Ligand binds and induces a conformational change.
Breaks hydrophobic interactions.
Each subunit of an ion channel receptor has how many TM domains?
4
The NT binding region is closest to what terminus for the ion channel receptor?
N
TM1 is closest to what terminus, TM4?
N
C
Botox works on which receptor type?
Ion channel
What are the ligands of ion channel receptors?
Serotonin (nicotinic - not a natural compound) Ach GABA Glycine
GPCR - general principles:
- Receptor binds a messenger leading to an ______ ___
- Opens a binding site for a signal protein = _-_______
- G-protein binds, is destabilized, then _____
induced fit
G-protein
split
The GPCR is how many polypeptides?
1
What does ligand binding to the GPCR cause?
Conformation change to expose G-protein binding area
GPCR - general principles:
- G-protein subunit activates ________ bound ________
- binsd to _______ binding site
- induced fit results in _______ of active site
- intracellualr reaction catalyzed
membrane bound enzyme
allosteric
opening
A GPCR is a ______ protein with __ TM domains.
single
7
The _-terminus is outside the cell, the _-terminus is inside for a GPCR
N
C
G-protein binding site is closest to what terminus?
C
What are the ligands of GPCR?
monoamines nucleotides lipids hormones glutamate Ca2+
Ach that binds to ion channel receptor is referred to as _______; when it binds to a GPCR _______
nicotinic
muscarinic
Draw the map of Receptor type to subtype for GPCR.
refer to slide 19
GPCR types and subtypes are not _______ distributed amongst tissues.
Equally
Heart muscle GPCR subtype?
B1 adrenergic
Fat cell GPCR subtype?
B3 adrenergic
Bronchial muscle GPCR subtype?
a1 and B2
Gi-Tract GPCR subtype?
A1, a2, B2
What residue is generally phosphorylated?
Tyrosine
A kinase linked receptor plays two roles, what are they?
Receptor
enzyme
RTKs are how many proteins?
1
Describe an RTK.
Extracellular N-terminus + ligand binding region
intracellular C-terminus and catalytic region
single TM domain
Kinase linked receptors - general principles:
- protein serves dual role - ______ + ________
- receptor binds messenger leading to an ______ ____
- protein changes shape and opens ______ site
- reaction catalyzed _______ cell
- _________ related to several cancers
receptor and enzyme induced fit active within overexpression
Ligands that bind to kinase linked receptors tend to be ______.
large
RTKs tend to _______.
dimerize
What are RTK ligands?
peptide hormones - ex: insulin and HGH
Describe the mechanism of action of intracellular receptors.
1 - mesesnger crosses memrbane 2 - binds to receptor 3 - receptor dimerization 4 - binds to co-activator 5 - complex binds to DNA 6 - Transcription switched on or off 7 - Protein synthesis activated or inhibited
Messengers for intracellular receptors tend to be what?
non-polar
TF can ______ or _______ transcription
induce or inhibit
The intracellular receptor has no ____ domain.
TM
Describe a typical intracellular receptor.
C-terminus
Steroid binding region
Zinc finger with DNA binding region
N-terminus
Why are there zinc fingers in intracellular receptors?
DNA has a negative charged, zinc is positively charged - allows for binding
What part of zinc allows it to coordinate?
Cystein residues with SH - allows S-Zn interactions
What are the ligands for intracellular receptors?
Steroid hormones Thyroid hormones Retinoic acid Vitamin D3 certain FA and phospholipids
