Seven transmembrane domain receptors Flashcards
Examples of seven-transmembrane domain receptors
- Beta androgenic receptor
- alpha androgenic receptor
- muscarinic cholinergic receptor
- VIP (vasoactive intestinal polypeptide (important for front part of the eye) and angiotensin II both affect blood vessels
- 5HT (Serotonin)
- DA (dopamine)
- SP (pain receptor and neurotransmitter in the spinal cord)
- Leutinizing hormone, folicle stimulating hormone, and thyroid stimulating hormone.
- Rhodopsin
- Platelet activating factor
Where on the receptor are binding sites for signaling molecules located?
Within the extracellular loops. This is also a great target for drugs and can influence the ability of the G protein to produce a result.
Internal loops are associate with what
The g-protein, microtubules, and cytoskeletal structures.
What happens when the first messenger binds to its receptor?
Intracellular calcium levels increase. Ca2+ is the second messenger and can enter through the membrane via Ca2+ channels or it can be released from the ER. (Calcium cannot be free in the cytosol because it can cause excitotoxicity- cell dies from over working itself).
An example of a cytotoxic disease, one where calcium is free in the cytosol and causes excitotoxicity.
ALS
Proteins that bind Ca2+
Calmodulin, calreticulin, and paravalbumin.
What is the role of a second messenger inside the cell
Modifies the signal, like a pansy scheme in reverse. (AKA it amplifies)
This is a slower ionotropic mechanism, but has a much wider effect with a low amount of stimulus.
Calsequesterin
Brings Ca2+ in and out (sequesters and isolates the calcium)
When Ca2+ is released from the ER, it is typically mediated by
IP3
4 alpha G-protein subunit types and their role when activated by GTP (Transducers)
Gs- adenylyl cyclase stimulation (increase CAMP)
Gi/o- adenylyl cyclase inhibitor (ion channels inhibitor CAMP phospholipase)
Gq- Phospholipase C activation. (increase DAG and IP3)
G1- Transducin cGMP phosphodiesterase found in the rod outer segment (activates Rho)
Kinase that can autophosphorylate itself
Tyrosine kinase can add a phosphate to itself or other tyrosine residues.
What does an activated protein kinase do?
Add Phosphates to serine or threonine residues to mobilize Ca2+
Protein kinases can be dependent on
CAMP, cGMP, PKc, calmodulin
Structure of tyrosine kinase
Exists as a single unit molecule (inactive monomers), but when it becomes a dimer, it can add phosphate groups to serine or threonine residues on molecules. Can mobilize Ca2+ and bring proteins to itself.
Inactive and active tyrosine kinase
Inactive- monomers not together
active- when phosphorylated, 2 monomers will form a dimer.
4 second messengers
cAMP, IP3, Arachindonic Acid (AA), and DAG
Requirements for a first messenger
Must be external
Calcium can be considered 2 things in a cascasde
Second messenger and a secondary effector
cAMP system-
- External signal
- Receptor it binds
- Transducer
- Primary effector
- Second messenger
- Secondary effector
- NE
- B-adrenergic receptor
- Alpha subunit is Gs, which means it acts to increase cAMP.
- Adenlylyl cyclase
- cAMP
- cAMP dependent protein kinase (PKA)
Phosphoionsitol system
- External signal
- Receptor it binds
- Transducer
- Primary effector
- Second messenger
- Secondary effector
- ACh
- Muscarinic ACh receptor
- Go (same Gi) ion channel inhibitor of cAMP phospholipases
- phospholipase C
- IP3 is created from PIP2 and goes to the ER to release calcium stores. Ca2+ activates DAG, which activates PKC.
- Ca2+ release from ER due to IP3 and Protein Kinase C activated by DAG
Arachinodic acid system
- External signal
- Receptor it binds
- Transducer
- Primary effector
- Second messenger
- Secondary effector
- Histamine
- Histamine receptor
- Go/i, which is an ion channel inhibitor of cAMP phospholipase
- Phospholipase A2
- Arachidonic acid
- 5 lipoxygenase, 12 lipoxygenase, and cyclooxyrgenase
cAMP pathway. PKA activation causes phosphorylation of ___
CREBP, cAMP response element binding protein, which modifies DNA.
What is adenylyl cycalse
An integral membrane bound enzyme that synthesizes cAMP when stimulated
IP3 is made by the hydrolysis of _____ and by which enzyme
PIP2, a phospholipid that is located in the plasma membrane by phospholipase C.
Calmodulin can bind to how many molecules of calcium?
- Discovered at St. Jude.
Rho
A type of GTPase that reorganizes the cytoskeleton through serine or threonine protein kinases
Eicosinoids are made where and derived from what by what enzyme
Made in the plasma membrane, derived from arachidonic acid by PLA2 (phospholipase A2)
Cyclooxygenase pathway (AA)
Produces prostaglandins, which have vascular and inflammation actions. Activates smooth muscle and regulates blood flow locally.
Produces thromboxjnes, which assist with blood clotting and other vascular actions.
Lipooxygenase pathway (AA)
Produces leukotrienes, which mediate allergic and inflammatory reactions.
Role of prostaglandins
Activates smooth muscle and regulates blood flow locally. Has vascular and inflammation actions
Produced through the cyclo-oxygenase pathway.
Structure and role of leukotrienes
Has 3 conjugate double bonds.
Involved with vascular contraction and permeability regulators. Mediates allergic and inflammatory response.
Activated through the lipo-oxygenase pathway.
NSAIDS and COX inhibits which AA pathway
Inhibits the cyclo-oxygense pathway, inhibiting the production of prostaglandins and thromboxjnes, both which play a role in blood clotting/blood flow and inflammation.
