Cellular Communication Flashcards
Which cell signaling method involves a chemical molecule released by one cell that acts locally on a neighboring cell?
Paracrine cell signaling
Which cell signaling method uses a chemical secreted into the blood that acts on a distant target cell?
endocrine cell signaling
Neurotransmitter signaling is a specific form of which type of cell communication method?
Paracrine signaling
Define signal transduction.
Signal transduction is the conversion of extracellular information into an intracellular chemical change.
Identify the 4 categories of receptor-based signal transducers.
- G protein-coupled receptors (GPCRs)
- Gated ion channels
- Enzyme-linked receptors
- Soluble nuclear receptors
What is another name for a chemical that binds to a receptor?
Ligand/1st messenger
What family of enzymes catalyzes the addition of a phosphate group to a molecule?
Kinases
Id the general feature of signal transduction shown on the card.
Specificity
Id the general feature of signal transduction shown on the card.
Feedback or desensitization
Id the general feature of signal transduction shown on the card.
Compartmentalization
Id the general feature of signal transduction shown on the card.
Amplification
Is thyroxine :
a. small hydrophilic molecules
b. lipophilic molecules
c. peptide/protein molecules
A. small hydrophilic molecules
Is Substance P:
a. small hydrophilic molecules
b. lipophilic molecules
c. peptide/protein molecules
C. Peptide/protein molecules
Is Calcitriol:
a. small hydrophilic molecules
b. lipophilic molecules
c. peptide/protein molecules
B. Lipophilic molecules
Is Angiotensin II:
a. small hydrophilic molecules
b. lipophilic molecules
c. peptide/protein molecules
C. Peptide/Protein molecules
Is aldosterone:
a. small hydrophilic molecules
b. lipophilic molecules
c. peptide/protein molecules
B. Lipophilic molecules
Is nitric oxide (NO):
a. small hydrophilic molecules
b. lipophilic molecules
c. peptide/protein molecules
B. Lipophilic molecules
Is insulin:
a. small hydrophilic molecules
b. lipophilic molecules
c. peptide/protein molecules
C. Peptide/protein molecules
Is Acetylcholine (ACh):
a. small hydrophilic molecules
b. lipophilic molecules
c. peptide/protein molecules
A. Small hydrophilic molecules
Is GABA:
a. small hydrophilic molecules
b. lipophilic molecules
c. peptide/protein molecules
A. Small hydrophilic molecules
Which categories of signaling molecules are stored in vesicles in the cell that synthesized the molecules?
- small hydrophilic chemical messengers
- peptide and protein chemical messengers
Which lipophilic chemical messengers are not derived from cholesterol?
- Eicosanoids
- Retinoids
- Endocannabinoids
Dopamine, Epi, NE, and the iodothyronines are derived from which amino acid?
Tyrosine
What are the 4 classifications of receptors?
Receptor classifications:
* ion channel
* GPCR
* Enzyme-linked receptor
* intracellular receptor
Describe the general architecture of the G-protein 2nd messenger system
- 1st messenger (extracellular signal)
- Receptor (responds to the extracellular signal)
- G protein (turns on/turns off an effector)
- Effector (activates/inhibits the 2nd messenger)
- 2nd messenger (primary intracellular signal)
- Enzymatic cascade
- Cellular response (causes a physiologic change)
Remember that 2nd messengers are tissue specific.
What 2nd messenger system is associated with teh alpha-1 receptor? What other receptors share a similar pathway?
Other receptors that share a similar 2nd messenger pathway:
* Histamine -1
* Muscarinic-1
* Muscarinic-3
* Muscarinic-5
* Vasopressin-1 (vascular)
What 2nd messenger system is associated with teh alpha-2 receptor? What other receptors share a similar pathway?
Other receptors that share a similar 2nd messenger pathway:
* Muscarinic-2
* Dopamine-2 (presynaptic)
What 2nd messenger system is associated with teh beta-1 AND beta-2 receptor? What other receptors share a similar pathway?
Other receptors that share a similar 2nd messenger pathway:
* Histamine-2
* Vasopressin-2 (renal)
* Dopamine-1 (postsynaptic)
Describe the autonomic innervation of the heart.
- SNS: The cardiac accelerator fibers arise from T1-T4
- PNS: Vagus nerve (CN X)
Id each as either a G-alpha or a G-beta/gamma subunit target effector
- adenylyl cyclase
- Gi,0 regulated potassium channels (GIRK)
- Beta-adrenergic receptor kinase (BARK)
- Voltage-gated calcium channels
- Phospholipase C (PLC)
- Phospholipase A2 (PLA2)
G-alpha subunit target effector
* PLC
* PLA2
* adenylyl cyclase
G-alpha beta/gamma subunit target effector
* Voltage-gated calcium channels
* GIRK
* BARK
Describe the activity in this step of the G-protein cycle.
Resting GPCR
GDP-alpha,beta,gamma G protein is associated with a 7-TM receptor. This is the resting, inactive, OFF state
Describe the activity in this step of the G-protein cycle.
GTP-load Alpha subunit
Ligand binding to the receptor causes a conformational change in the receptor. The recepotr conformation change promotes exchange of GDP for GTP on the alpha subunit.
Describe the activity in this step of the G-protein cycle.
Activate/ON G protein
The activated G protein dissociates from the 7-TM receptor. The GTP-loaded alpha subunit dissociates from teh beta/gamma complex.
Describe the activity in this step of the G-protein cycle.
Alpha subunit interacts with Effector
The GTP-alpha subunit diffuses to an interacts with its downstream effector.
Describe the activity in this step of the G-protein cycle.
Beta/Gamma can interact with an effector
The beta/gamma complex diffuses to an interacts with a downstream effector.
Describe the activity in this step of the G-protein cycle.
GTPase activity restores the resting state
The intrinsic GTPase activity of the subunit hydrolyzes GTP to GDP + Pi. The heterotrimeric complex is reformed and associates with the 7-TM receptor.
Which heterotrimeric G protein subunit contains the intrinsic GTPase activity?
The alpha subunit
What is the signal transduction sequence through GPCRs?
First messenger (ligand) –> GPCR –> Effector –> Second messenger –> cellular response
List the 4 subfamilies of heterotrimeric G proteins.
- Gs
- Gi.0
- Gq,11
- G12,13
Identify each as: cAMP, DAG, IP3, or ionized calcium
- Lipid second messenger
- Generated from PIP2 and diffuses in the cytoplasm
- Targets ligand-activated Ca++ channels on the ER
- Activates PKA
- IP3 releases it from the ER
- Removed from the cytoplasm by pumps and transporters
- Binds to calmodulin
- ATP is the precursor
- Generated from PIP2 and stays in the plasma membrane
- Adenylyl cyclase catalyzes production
cAMP
* Activates PKA
* ATP is the precursor
* Adenylyl cyclase catalyzes production
DAG
* Lipid second messenger
* Generated from PIP2 and stays in the plasma membrane
IP3
* Generated from PIP2 and diffuses in the cytoplasm
* Targets ligand-activated Ca++ channels on the ER
Ionized calcium
* IP3 releases it from the ER
* Removed from the cytoplasm by pumps and transporters
* Binds to calmodulin
Which G protein alpha subunit activates adenylyl cyclase?
G-alpha S activates adenylyl cyclase
Which 2 calcium transporters are found in the plasma membrane?
- The sodium-calcium exchanger (NCX)
Ca++ ATPase pump (pump, PMCA)
What enzyme family catalyzes the addition of a phosphate group to a substrate?
Kinases catalyze the addition of a phosphate group to their substrates
What enzyme produces IP3 and DAG from PIP2?
Phospholipase C (PLC)
The two types of synapses in the human body are: (select 2)
a. chemical
b. thermal
c. mechanical
d. electrical
Electrical and chemical
There are 2 types of synapses in the human body - electrical and chemical.
Electrical, chemical, mechanical, and thermal are all types of energy, but only chemical and electrical synapses are currently known to exist in the human body.
Identify each as either an ionotropic receptor or metabotropic receptor
- Nicotinic AChR
- Conformational change sets in motion a biochemical cascade
- 5-HT3R
- Slower synaptic response
- Opioid receptor
- Conformational change gates a pore
- Muscarinic AChR
- Fast synaptic response
Ionotropic Receptor
* Nicotinic AChR
* 5-HT3R
* Conformational change gates a pore
* Fast synaptic response
Metabotropic Receptor
* Conformational change sets in motion a biochemical cascade
* Slower synaptic response
* Opioid receptor
* Muscarinic AChR
List two gases that are unconventional neurotransmitters.
Nitric oxide (NO) and carbon monoxide (CO)
What structure connects cells at an electrical synapse?
Gap junctions (connexions form gap junctions)
Which protein in the docking complex is the calcium sensor?
Synaptotagmin
Name 3 signals that open pores in gated ion channels.
- membrane voltage (electrical)
- chemicals (ligands)
- pressure (mechanical)
Id each neurrotransmitter as a biogenic amine, AA neuropeptide, or nonconventional:
1. Norepinephrine
2. vasoactive intestinal peptide (VIP)
3. Serotonin
4. Glycine
5. Dopamine
6. opioids
7. Nitric oxide (NO)
8. Substance P
9. Glutamate
10. Anandamide
11. GABA
Biogenic amine
* norepinephrine
* serotonin
* Dopamine
Neuropeptide
* VIP
* Opioids
* Substance P
Amino acid
* Glycine
* Glutamate
* GABA
Nonconventional
* NO
* Anandamide
Where are nicotinic ACh receptors NOT located?
a. autonomic ganglia
b. neuromuscular junction
c. chromatin cells in the adrenal medulla
d. sinoatrial node
D. Sinoatrial node
Nicotinic ACh receptors are ligand-gated ion channel receptors (ionotropic receptors). They’re located at the NMJ in skeletal muscles, at autonomic ganglia, on chromatin cells of the adrenal medulla, and in the CNS.
At the SA node, ACh binds to muscarinic ACh receptors, which are GPCRs (metabotropic receptors)
Identify each as belonging to a muscarinic AChR OR a nicotininic ACh
- nonselective cation channel
- presynaptic autoreceptors
- metabotropic
- slowed spontaneous depolarization of SA node
- binding of 2 ACh molecules for full activation
- airway smooth muscle
- ionotropic
- coupled to heterotrimeric G protein
- secretion of catecholamines from adrenal medulla
- neuromuscular junction
Nicotinic AChR
* nonselective cation channel
* binding of 2 ACh molecules for full activation
* ionotropic
* neuromuscular junction
* secretion of catecholamines from adrenal medulla
Muscarinic AChR
* presynaptic autoreceptors
* metabotropic
* slowed spontaneous depolarization of SA node
* airway smooth muscle
* coupled to heterotrimeric G protein
What is the primary inhibitory neurotransmitter in the spinal cord?
glycine
Which neurotransmitter is associated with excitotoxicity?
Glutamate
Which GABA receptor is metabotropic?
GABA-B receptor
Glutamate is converted to GABA by what type of enzymatic reaction?
Decarboxylation
What two binding sites are located in the NMDA receptor channel (pore)?
- Mg++
- Ketamine/PCP
All catecholamine neurotransmitters are derived from which amino acid?
L-tyrosine
What enzymatic reaction is present in ALL biogenic amine neurotransmitter biosynthesis?
Decarboxylation
Identify the 2 subtypes of monoamine oxidase (MAO).
- MAO-A preferentially metabolizes dopamine, serotonin and epi.
- MAO-B metabolizes dopamine more rapidly than NE and serotonin.
What end-product of NE metabolism is excreted in the urine?
Vanillylmandelic acid (VMA)
The largest concentration of dopaminergic neurons in the brain is in what structure?
Substantia nigra
What cells in the adrenal medulla release epinephrine into the circulation?
Chromaffin cells
Ondansetron targets which specific serotonin receptor?
The ionotropic 5-HT3 receptor
Are GTP and ATP classified as purines or pyrimidines?
Purines
What enzyme converts ATP to adenosine in the synaptic cleft?
Ectonucleotidase
Are all neuropeptide receptors inotropic or metabotropic?
Metabotropic
What signaling complex activates nNOS?
Ca++/CaM (calmodulin) complex
An activity-dependent increase in synaptic efficacy is called:
Long-term potentiation
What cytosolic heme-containing enzyme is activated by NO?
soluble guanylyl cyclase (sCG)
