Chapter 18

What are the 5 types of biosignaling?
1.   communication
2. Signaling via   molecules
3.   intercellular communication
4.   vesicles
5.  communication

What is an example of direct cell-to-cell communication?

Two types of receptor-mediated intercellular communication are   receptors and   receptors

Examples of extracellular vesicles include  ,  ,  ,
  vesicles.

  modes of action not well known at this
time, but soon will become important – especially in the fields
of chronic diseases, chronic infections, acute infections,
cardiovascular diseases and mental illnesses

“A key is useless without a matching lock, and
an   is useless
without a   in its target cell.

 : a molecule on the cell surface, in the
cytoplasm or in the nucleus that interacts with
other molecules and produces a response.

What is an example of a fast response speed for a ligand and receptor?

What is an example of a slow response speed for a ligand and receptor?

  a molecule that binds to its
receptor

  a ligand that causes the receptor to activate a response in the cell.

  a ligand that causes thereceptor to become inactive.

What are 8 examples of endogenous ligands?

What are the three opiod agonists of µ-receptor, endogenous ligand β endorphin, endomorphine-1.2?

Beta blockers function as  .

What are two examples of inhibitors of Beta-adrenergic receptors?

What are the endogenous ligands for β endorphin, endomorphine-1.2?

Where are membrane bound receptors located? How do they work?

-They are embedded in the membrane with ligand facing the  
-Binding on the outside activates the receptor, sending a singal  of the cell

Intracellular receptors: ligands can transverse the plasma membrane and bind
receptors  

Cytoplasmic receptors - a type of   receptor that bind ligands in cytoplasm, becomes activated, then move into the   to  

Nuclear receptors - a type of   receptor were the ligand enters the nucleus to bind its receptor, activates it, then bind   & promote  

 receptors - Involved in rapid synaptic signaling between
electrically excitable cells.

G-protein coupled receptors (GPCR) -  transmembrane protein,   regulate the activity of a target protein through a   ( )

Enzyme-linked receptors -   transmembrane protein, Function   as   or directly associated with  they activate

Ligand-gated ion channels are what type of receptor?

G-protein-coupled receptors are what type of receptor?

What type of cells are ligand-gated channels most important for?

How do ligand gated challenels transduce signals?

What type of response do ligand-gated channels allow for (slow or fast)?

What are the 5 steps for ligand channel functioning?
1. Before binding, it is in a   conformation
2. Ligand binds to ligand  site
3. Channel  so that ions can pass and induce a response
4. Ligand 
5. Protein conformation of channel  

What type of ion channels are used by neurotransmitters?

What are the four steps of neurotrasmitter signaling?
1. Action potential at   axon
2. Vesicles loaded with neurotransmitters fuse with   and release  
3. Ligand binds to  site at  channel
4. Ions pass through and alter the  , triggering voltage gated channels to respond

Na+ channel that allows positive ions to flow  cell   membrane

1. Cl- channels - allow negative ions to flow   membrane
2. K+ channels - allow positive ions to flow    membrane

TEST QUESTION: What are cholinergic receptors? Where are they found?
Receptors activated by  . They are found in the   and  

TEST QUESTION: What are the two subtypes of cholinergic receptors? What are they named after?
 and  . They are named after the drugs they with.

TEST QUESTION: Nicotinic receptors (nAChR) are    

TEST QUESTION: Nicotinic receptors (nAChR) are made of   subunits, arranged   around a  

TEST QUESTION: What are the two types of nicotinic receptors (nAChRs)
1.  type
2.   type

TEST QUESTION: Neuronal-type nicotinic receptors (Nn): found in both   and  : located   from other types of receptors

TEST QUESTION: Muscle-type nicotinic receptors (Nm): are found   on neuromuscularjunctions: responsible for  .

TEST QUESTION: Muscarinic receptors (mAChR) respond to both   and   and are metabotropic receptors, or  , that use   to
propagate the signal.

TEST QUESTION: How many subtypes of muscarinic receptors are there
  subtypes,   (We need to know subtypes  ,  , and   for the exam)

TEST QUESTION: A M1 receptor is   protein-coupled. It increases  . It is found in the  .

TEST QUESTION: A M2 receptor is   protein-coupled. It increases  

TEST QUESTION: A M3 receptor is   protein coupled. It increases  

Briefly glance at chart in case she frames a question around sympathetic versus parasympathetic systems and one of the receptors she talks about

In the sympathetic nervous system, pre-ganglionic neurons release  
that binds to   in post-ganglionic neurons on target cells

In the sympathetic nervous system, post-ganglionic neurons then release  ( ) that go on to bind receptors at target tissues.

Some sympathetic post-ganglionic neurons release , which binds to   receptors on target cells.

In the parasympathetic nervous system, pre-ganglionic neurons release   that binds to   in postganglionic neurons

In the parasympathetic nervous system, post-ganglionic neurons then release
  that go on to bind   on target cells

Describe what happens at the neuromuscular junction in the somatic nervous system (5 steps)
1. Ach is released following an  
2. Ach binds to nicotinic receptors on  , causing contraction
3. Nitchontine receptors are   receptors with  units
4. 2 AChs bind to  alpha units, opening the channel
5. They are excitatory ligand gated ion channels that let  and  (causes DEPOLARIZATION and action potential)

Voltage-gated  are essential contributors to neuronal
 , making them the most commonly targeted ion channel family by toxins found in  

What are two examples of acetylcholine nicotine receptor anatagonists found in nature?
1.  
2.  

A voltage gated soudium channel is also referred to as a  

CLINCIAL CORRELATION: The naturally occurring marine toxinstetrodotoxin (TTX) and saxitoxin (STX) interact strongly with the   region to occlude the   pathway.

A g-protein coupled receptor has   polypeptide chain with   transmembrane (TM) domains.

In a g-protein coupled receptor, the  terminal of this long protein is exposed to the outside of the cell and the   terminal is exposed to the inside of the cell.

G-protein receptors can have one signal molecule that can interact with many different types of receptors and have  

  are the largest family of cell-surface molecules involved in signal transmission

In a trimeric receptor, there are  possible outcomes based on the rank order of  concentration

GPCRs act  on a second protein (enzyme or channel)

A GPCR use a   protein

A trimeric GTP-binding protein has   and   subunits that have   domains that anchor them to the   of the plasma membrane and a   binding domain

When a trimeric GTP-binding protein is GDP bound, it is  . When it is GTP bound, it is  

A muscarinic receptor is also called a  . They interact with cytoplasmic proteins after binding 

What are the three subunits of G-proteins?
1.  
2.  
3.  

The alpha and gamma subunits of g-proteins are anchored
to   and interact with the
 .

The alpha unit of a g-protein is bound to   (  state)

The activated alpha of a g-protein is able to  

To act on other proteins, the alpha subunit of a g-protein uses the
energy from  , which leaves   bound and sends
alpha back to beta-gamma.

The cAMP-dependent pathway, also known as the adenylyl cyclase (AC) pathway, is a   signaling cascade

What are the 4 steps of the Gs cAMP-dependent pathway
1. M1 activates the   and interacts with on membrane
2. Activated AC uses ATP to make   which  
3. PKA has a catalytic subunit that   other proteins to trigger a response
4. Beta 2 adrenergic receptors bind to  and are coupled with GS (stimulates adenylate cylase)

Describe the 5 steps of the activation of a Gq alpha subunit
1.  ,  , and   activate the Gq-alpha subunit, leading to an interation with  
2. PLC clevaes   into   and 
3. IP3 makes   channel open, causing  
4. DAG binds to   which needs   to activate
5. PKC   other protiens and triggers cell response

M1 or M4: Activation of Gi- alpha subunit also interacts with  
and   it

For a receptor interacting with a Gi subtype, inhibition of AC causes a
  feedback on effects of Gs.

Clinical Correlation: Histamine GPCRs are involved in allergies and asthma because histamine stumulates  . Treatment is a   that brochodilates.

In asthma treatment, after the physiologic effect is
accomplished (ex: vasodilation),
receptor desensitization occurs
via  

In the treatment of asthma, the   number of the airway smooth
muscle cell surface is  by endocytosis (internalization) or degradation (downregulation)

In asthma treatment,   also affect the regulation of histamine GPCRs through heterologous regulation, leading to a   towards vasodilation.

Protease-activated receptors (PARs) are a
unique family of GPCRs that are  following   of
their extracellular  .

What are the 5 important functions of protease activated receptors?

What are the 4 ways that enzyme linked receptor signaling is tightly regulated?

Protease Activated Receptors (PARs) was first described in   and
associated with   disease.

During injury, the activated platelets aggregate and release a cascade of  , which increase  concentration. Thrombin promotes the formation of a
 in an attempt to fix the lesion.

The part of the GPCR that is
(anchored in the membrane) now has
an exposed  site, so it
activates itself and causes 

One thrombin molecule can activate   and lead to ampolification

Receptor tyrosine kinases (RTK2) phosphorylate Tyr
residues on the  of the receptor.

Before binding ligands, the receptor tyrosine kinases are found as
individual units on the  

After binding ligand (hormone), the receptor tyrosine kinases dimerize, which causes the cytoplasmic domains to be   and  

In a receptor tyrosine kinase, the cytoplasmic domains  each other

Receptor Tyrosine Kinase (RTK)s =   genes

What is the largest of the enzyme coupled receptor class:?

A tyrosine kinase has  transmembrane segment. Can activate  signaling pathways.

What are the 6 shared steps of tyrosine kinase phosphates?
1. ligand binds the receptor
2. receptor joins and  
3. intrinsic enzyme, the  , becomes active
4. Receptor  the opposite tyrosine residues
(= ).
5. The phosphorylated tyrosine residues activate the   signaling
proteins.
6. Activated intracellular signal proteins trigger an intracellular
signaling pathway

What are 3 features of receptor tyrosine kinases?
(1) High   affinity
(2)  activity that causes autophosphorylation.
(3) Activation of effectors to generate a  

What are the four steps of insulin action?
1. Food intake
 
blood glucose
2. stimulates
pancreas to   insulin
into the
bloodstream
3. Insulin finds
 
expressing IR
4. IR kinase
enzyme is
activated which  

Unlike other
RTKs, the
insulin receptor
is a , but
it’s just not
active before
binding insulin.

When blood glucose levels are high, the pancreas releases insulin which is a  / 

Binding of inulin in target tissues receptors activates the   of their cytoplasmic tails.

Insulin binds to the extracellular
  and the  auto-phosphorylate.

Insulin uses energy from ATP to
transfer   to the   of the receptor.

Phosphorylated insulin receptor sends
signal to causes mobilization of
  transporters.

Vesicles with   transporters fuse to the membrane, allowing glucose toenter the target cells.

What are the four insulin effectors in order?

Binding of insulin is followed by
internalization of the  

Once inside the cell, the insulin is degraded in the  

Some of the insulin receptor gets degraded as well, but most are   back to the cell surface.

Interferon receptor with Janus kinase involving the   signaling pathway. Interferon is the first line of defense against  

During chronic stress, IFN signaling is   and the individual becomes more prone
to developing  .

Intracellular receptors are only available to   that diffuse through the
membrane

All intracellular receptors act as ligand-activated  

Steroid receptors are located in the  .When steroid binds, the complex is translocated to the nucleus (via  ). In the nucleus, they act on the DNA as enhancers of  

What are the two groups of intraceullar receptors?

Thyroid hormones receptors normally sit on
the DNA, gene expression.

When  binds, it displaces
a co- repressor from the receptor and
allows binding of co- activator protein,
which   gene expression.

The tyroid hormone receptors have a   that binds   ( ) and a   region that interacts with the hormone.

The DNA sequences that are bound by
these thyroid hormone receptors are called