2. Receptors G-protein coupled receptors Ion Channel Receptors
Receptor-enzymes Cytosolic-nuclear receptors 3. G-protein coupled
receptors 4. G-protein coupled receptor: GPCR Examples: Adrenergic
receptors Muscarinic ACh receptors GABAB receptors Metabotropic
Glutamate receptors Dopamine receptors Metabotropic Serotonin
receptors 5. G-protein coupled receptor: GPCR More
exampleshormones: Angiotensin receptor Bradykinin receptor Thrombin
receptor FSH receptor LH receptor TSH receptor ACTH receptor 6.
GPCR structure A single subunit with 7 transmembrane segments out
in 7. A depiction of how GPCRs activate signaling 8. Ligand + GPCR
GPCR* GPCR* abg a + bg signaling abg Heterotrimeric GTP-binding
protein (G protein) GPCR G-protein coupled receptor signalin g
Another depiction of how GPCRs activate signaling 9. Heterotrimeric
GTP-binding proteins cycle between GTP- and GDP-bound state Binding
of ligand to G-protein coupled receptor facilitates exchange of GTP
for GDP, a and bg dissociate a b g GDP a b g GTP INACTIVE ACTIVE
10. Heterotrimeric G proteins Activated by binding of ligand to
7-transmembrane receptor (G-protein coupled receptor) Ligand
binding causes dissociation of a and bg subunits Dissociation
allows GDP to exchange for GTP GTP binding causes conformational
change, a subunit can now interact with effector (e.g. AC) GTP is
hydrolyzed to GDP, a subunit dissociates from effector Signal is
terminated 11. Adenylate cyclase Membrane protein makes cAMP from
ATP ATP cAMP 12. Three major families of G-proteins Gs couples to
Adenylate Cyclase stimulates AC activity increases cAMP activates
Protein Kinase A Gi couples to Adenylate Cyclase inhibits AC
activity decreases cAMP inhibits Protein Kinase A Gq couples to
Phospholipase C increases diacylgyclerol (DAG) increases IP3
increases intracellular Ca2+ 13. Gs Gi Gq b-adrenergic receptor
ACTH receptor FSH receptor a2-adrenergic receptor M2 muscarinic
receptor a1-adrenergic receptor M1, M3 muscarinic receptors
Angiotensin receptor cAMP PKA activity cAMP PKA activity PLC
activity DAG, IP3 Ca2+ PKC activity G-protein Receptor examples
Signaling pathway 14. cAMP-dependent stimulation of glucose
liberation from glycogen 15. bAR a b g GTP AC PKA cAMP-dependent
stimulation of cardiac muscle contraction Ca2+ Ca2+ Ryanodine
Receptor Sarcoplasmic reticulum bAR = b-adrenergic receptor 16.
cAMP is constantly inactivated by phosphodiesterase (active)
(inactive) Theophylline blocks the phosphodiesterase 17.
Phospholipase C activation produces Diacylglycerol and IP3 PI 4,5
biphosphate (PIP2) Plasma membrane lipid plasma membrane
Diacylglycerol (DAG) Inositol 1,4,5-triphosphate (IP3) cytosolic
messenger plasma membrane 18. a1-adrenergic receptors acting on
vascular smooth muscle: PLC IP3 Ca2+ calmodulin myosin light chain
kinase Myosin-P contraction An example of the Gq signaling pathway
19. IP3 receptors: intracellular calcium channels 20. Controlling
intracellular calcium levels IP3 receptors Ca2+ Intracellular Ca2+
levels are
