Week 2 Flashcards
What are the types of intercellular communication (5)
Autocrine
Paracrine
Contact-mediated
Synaptic
Endocrine
What is Kd
Binding affinity of a receptor
When binding saturation is 50%
(The lower the higher affinity, cause less dose is needed for action)
What is Ec50
Characterizes potency of a drug
When bio response is 50%
Lower Ec50 is more potent
(Effective conc. 50)
Biological response of Agonist, Partial Agonist, and Antagonist.
Agonist: 1 (100%)
P.Agonist: 0.5 (50%)
Antagonist: 0 (0%)
Antagonists can be
Neutral Antagonists
Inverse Agonists
Cariprazine
Stimulates / Inhibits D3/D2
Agonist / Antagonist
Works like dopamine but only 40-60%
Depression and Schizophrenia
What are the Vasopressin Receptors
V1- Smooth Muscles
V2- Kidney
Why do we administer Desmopressin if Antidiuretic Hormone is Low
Because administering Vasopressin directly would mean that both V1 and V2 receptors would be affected.
So smooth muscles and the kidneys would be affected.
Desmopressin
V2 Receptor Agonist
GPCR Steps
1) Agonist Binds R —-> R*
2) Receptor / G-protein Interaction a-GDP to a-GTP.
3) G-protein dissociates from Receptor.
4) a and by subunits dissociate.
5) Subunits interact with effectors.
6) Termination and subunits bind again.
What converts GDP to GTP
GEF
Guanine exchange factor
e.g: Active G-prot coupled Receptor
What inactivates GTP to GDP
GAP
GTPase Activating Protein
What types of receptors are Adrenergic R
All G Protein coupled receptors
Gs Proteins Examples
B - Adrenergic R
ACTH R
Glucagon R
What does PDE do? What can inhibit it>
Metabolizes cAMP to AMP
Caffeine, leads to more alertness.
G i/o Protein Examples
a2 - Adrenergic R
Opiate R
Cannabinoid R
Somatostatin R
Effects of G i/o Proteins
Inhibition of Adenylyl Cyclase (no cAMP)
Activation of K Channels
Inhibition of Ca Channels
Phospholipase A2 Activation
3 Paths of Arachidonic acid Signaling
Cyclooxygenase
Lipoxygenase
Epoxygenase
What does Arachidonic acid in cyclooxygenase path produce?
Prostaglandins
Therefore, blocking COX helps with fever inflamation and pain.
What Mediates Transducin and Gustducin actions?
cGMP —> GMP
G q/11 Protein Examples
a1 R
Angiotensin R
Events after Gq/11 activation
1) a subunit activates Phospholipase C.
2) PLC acts on PIP2
3) DAG+ IP3
4) DAG activates PKC
5) IP3 –> R –> Opens Ca flux from ER to cytoplasm.
What does Capacitive Ca entry do?
Ensures that Ca stores in cell (ER) do not get depleted
Capacitive Ca mechanism / SOC
STIM-1 Ca Sensor
Orai-1 Ca Channel
What happens in response to increased Ca (Signal)
Ca binds Calmodulin, forms complx
Ca-Calmodulin activate CAM Kinases
CAMK phosphorylate target proteins
Ga 12/13 Protein examples
Thrombin R
Angiotensin R
G 12/13 Protein mech
1) a 12/13 - GTP activates GEF (Rho)
2) Rho - GTP
3) Rho Kinases
Actions of Gt (Transducin) and Gg (Gustducin) Protein
1) at/g - GTP Activate PDE
2) PDE metabolizes cGMP to GMP
What is Desensitization
The deactivation of a G-protein coupled receptor
2 Methods of desensitization
Agonist dissociation
B-Arrestin Binding
Types of Cholinergic receptors
Nicotinic / Ion channels
Muscarinic / GPCRs
Receptor Tyrosine Kinases Ligands
Growth Hormone
Insulin
Activation mech of Tyrosine Kinase receptors
1) Agonist Binding
2) Receptor dimerization
3) Autophosphorylation of Tyr
RAS Pathway
1) Ligand binds to RTK
2) RTK autophosphorylation
3) SH2 binds phosphotyrosine
4) SOS binds (GEF)
5) RAS (GDP to GTP)
6) MAPK Phosphorylates cytosolic proteins and nucleus.
What inhibits apoptosis and keeps cell survival
PI 3 Kinase
What type of R is ANP-receptor
Guanylyl cyclase R
Guanylyl Cyclase / ANP Receptor mech
1) ANP (Agonist) binds GC.
2) GC makes cGMP
3) PKg —-> Smooth m relaxation
What is JAK
Tyrosine Kinase
(Janus Faced Kinase)
Cytokine receptor examples
Growth Hormone R
Prolactin R
JAK can phosphorylate
Receptors
Other JAK
STAT proteins
What does phosphorylation of STAT proteins lead to?
This effects the nucleus
Leads to up/down reg. of gene expression (Slow)
What type of Agonists are used for Intracellular R
Lipid permeable agonists
Types of Intracellular Receptors
Cytosol (Type-I) / Glucocorticoid R
Nucleus (Type-II) / Thyroid HR R
Can lipid permeable Agonists be used other than Intracellular receptors
Yes, in Plasma m. R (Faster)
in Cannabinoid R and Prostaglandin R
NO Signaling
1) NO made by NOS
2) NO binds Guanylyl Cyclase
3) GTP —> cGMP
(Leads to vasodilation)
2 Examples of Gene regulation
cAMP
JAK - STAT Pathway
5 mechanisms of Intracellular Ca homeostasis
1) Gq
2) PLC
3) Voltage gated channel
4) Ligand-Gated channels
5) CICR
6) RYR (Ryanodine R)
OFF mechanism of Ca signaling
1) SERCA (Sar/endo Ca ATPase)
2) PMCA (P.m. Ca ATPase)
3) NCX (Na/Ca exchanger)
What activates the endocytosis of a GPCR
Arrestin Binding
