Signal Transduction Flashcards
what is the homeostatic reflex arc?
Note the autonomic response
Ligands: agonist vs antagonist
- signal increase
- signal decrease
What are the classes for Biogenic Amine NTs?
- catecholamines (NorE, Epi, Dopamine)
- Esters (Ach)
- Indolamines (Histamine, 5-HT)
Catecholamines are sympathetic or parasympathetic?
Post-ganglionic sympathetic
Acetylcholine is used where?
- autonomic ganglia
- skeletal muscle
(postganglionic parasympathetic)
What are the peptide NTs?
dont need to memorize NVM
Amino Acid NTs
- Excitatory (glutamate, Aspartate)
- inhibitory (GABA, Glycine)
NT: other
what are the steps of G-protein Cycling?
- agonist binds receptor in lock and key
- receptor associates with G-protein
- GTP enters and replaces GDP
- Aplha-GDP and Beta/gamma subunits dissociate and start activating downstream protiens
- alpha subununit hydrolyes GTP
- subunits reunite
the alpha subunit GTPase activity- this acts like a timer. Therefore, the subunit is on a timer, and the signal does not stay on forever.
Different alpha subunits …?
have different downstreatm effects (2nd messengers/ion channels)
B-gamma subunit
???
slide 13 (relisten)
What are the three alpha subunit families?
s- stimulates AC
i- inhibits AC
q- phospholipidase C (ca2+ levels increase in the cell??)
What does Adenylate Cyclase and cAMP do?
AC converts ATP-Mg2+ to cAMP
cAMP activates PKA
phosphodiesterases (PDE) get rid of CAMP (regulation). Everything is a balancing act.
How does PKA activity affect function?
varies- can increase or decrease (enzymes, pumps, channels)
what are the families of Adenylate cyclase?
ADCY1, ADCY2, …, ADCY10, just note that there are many families
isoforms differ in acticity modulation??
what are the components of the PLC system?
the end result: increased intracellular Ca2+
What are the components of the Guanylate Cyclase system?
- ca2+ calmodulin complex activates NO synthase (CM-Ca2+)
note the presence of PDE to break down cGMP (Viagra is an example, it prevents breakdown of cGMP resulting in vasodilation)
NO is made where and acts where?
- Vascular endothelial cells
- nearby smooth muscle cells
it increases cGMP resulting in vasodilation
ACh is found where?
PNS and CNS
What two types of receptors does ACh bind?
- nicotinic receptor
- muscarinic receptors
Nicotinic Receptor Mechanism
ACh opens
What are the subtypes of nicotinic receptors?
- alpha and beta subunits
- Skeletal muscle (N1 or Nm)
- Autonomic ganglia (N2 or Ng)
other ligand gated channels
Muscarinic Receptors
- not channles
- assoc. with G-proteins
- 5 subtypes (m1-m5)
m1,3,5 receptors function
Activate Phospholipase C through Gq
PLC activation —> increased IP3 –> increased intracellular Ca++
Increased intracellular Ca++ —>
Activation of Ca++-sensitive K+ & Cl- channels.
* Generally, cause smooth muscle contraction
m2 and m4 receptor function
- Gi -coupled inhibition of adenylate cyclase
- Gi -coupled activation of certain (e.g., GIRK) K+ channels ??
Sometimes you see these called** Gk** or Go coupled
* Classic example will be M2 receptors in heart
* Generally, have an inhibitory effect
What are the three familes of Adrenergic Receptors?
sympathetic Nervous System
- G-protein Association
Adrenergic receptor are coupled to cellular processes through…?
G-proteins
B-Adrenegeric receptors are coupled to which G protein?
what is the end result?
- Gs, which stimulates cAMP which increases PKA act.
- tend to relax smooth muscle
alpha1 adrenergic receptor is couples to what G protein?
Gq, which activates PLC, which increases either
- IP3 and DAG
- **Ca2+ channels **
tend to contract smooth muscle
alpha 2 adrenergic receptor
Gi -mediated inhibition of adenylate cyclase.
* Decreased cAMP
* Decreased PKA activity.
Gi – activates K+ channels
* Hyperpolarizes cell membranes
* Classic example is presynaptic inhibition of neurons
- tends to inhibit (i.e. pre-synaptic neurotransmitter release)
Adrenergic Receptor Review
