Cellular Communication Flashcards
Types of intercellular communication by chemicals
Endocrine
Paracrine
Autocrine
Signaling molecule is secreted by a cell and transported through the circulation where it acts on a distant target cell
Endocrine cell signaling
Chemical signaling molecule is released by one cell and acts locally to regulate the behavior of a neighboring cell
Paracrine cell signaling
A cell responds to a signaling molecule that it also produced
Autocrine cell signaling
Any chemical that binds to a receptor is a ____
Ligand
What is another name for ligand?
First messenger
What results from signal recognition and transduction of an extracellular message ?
Second messenger or
Catalytic cascade
Four types of receptor-based signal transducers
- Transmembrane G protein couple receptors
- Transmembrane ligand-gated ion channels
- Transmembrane enzyme-linked receptors
- Soluble intracellular (nuclear) receptors
What are the four categories of small, hydrophilic chemical messengers?
Amino acids
Biogenic amines
Choline esters
Idothyronines
Four examples of amino acid chemical messengers
Glycine
Glutamate
GABA
Aspartate
Five examples of biogenic amine chemical messengers
Dopamine
Norepinephrine
Epinephrine
Serotonin (5-HT)
Histamine
Example of a choline ester
Acetylcholine
Two idothyronines
Thyroxine (T4)
Triiodothyronine (T3)
What chemical messengers are derived from tyrosine?
Dopamine
Norepinephrine
Epinephrine
Idothyronines (T4 and T3)
What are some general features of small, hydrophilic chemical messengers?
Polar molecules that are ionized at physiologic pH
Need cell-surface receptors to cross plasma membranes
Stored in vesicles in the cells that synthesized them
Typically released by exocytosis (excluding T3 and T4)
Three general categories of lipophilic chemical messengers
Steroids
Eicosanoids
Other
Examples of endogenous steroids
Aldosterone
Cortisol
Testosterone
Progesterone
Estrogens
Examples of eicosanoids
Prostaglandins
Leukotrienes
Thromboxanes
Two miscellaneous lipophilic chemical messengers
Vitamin D3
Retinoids
What are general characteristics of peptide and protein chemical messengers?
Usually polar (hydrophilic)
Do not readily cross plasma membranes = usually bind to cell surface
Synthesized as precursor molecules
Stored in vesicles in the cells that synthesized them
Circulate in the blood stream as unbound molecules
What is the sequence of signal transduction through G protein-coupled receptors?
First messenger (ligand) > GPCR > Effector > Second messenger > Cellular response
What are the three components of signal transduction through GPCRs?
- A plasma membrane receptor with seven transmembrane helical segments
- A guanosine nucleotide- binding protein activates the effector enzyme or pathway
- An effector (usually an enzyme) in or associated with the plasma membrane that generates an intracellular second messenger
What are the heterotrimeric G protein families?
Gs
Gi
Gq
G12, 13
Enzyme that produces cyclic adenosine monophosphate
Adenylyl cylase
Enzyme that produces inositol triphosphate (IP3) and diacylgycerol (DAG)
Phospholipase C
Enzyme that produces eicosanoids
Phospholipase A2
Intercellular junction that helps the nervous system communicate
Synapse
Two types of synapses
Chemical
Electrical
Which type of synapse is most prevalent?
Chemical
Signals flow directly from one cell to another in a bi-directional fashion
Electrical synapses
Signal travels in one direction from the presynaptic membrane to the postsynaptic membrane across a synaptic cleft
Chemical synapses
Two types of receptors at chemical synapses
Ion channels (ionotropic)
Heterotrimeric G proteins (metabotropic)
Three signals that open pores in gated ion channels
Membrane voltage (electrical)
Chemicals (ligands)
Pressure (mechanical)
Primary neurotransmitter of peripheral efferent neural pathways
Acetylcholine
Where does ach synthesis take place?
Presynaptic nerve terminal
Type of Ach receptor that is ionotropic
Nicotinic
Type of Ach receptor that is metabotropic
Muscarinic
Ach substrates
Acetyl-CoA
Choline
Primary excitatory neurotransmitter in the brain
Glutamate
Responses to glutamate
Motor neuron activation
Pain pathway transmission
Elevated pain sensation (hyperalgesia)
Memory formation
Cerebral neurotoxicity
Primary inhibitory neurotransmitter in the brain
GABA
Primary inhibitory neurotransmitter in the spinal cord and lower brainstem
Glycine
Where is glutamate synthesized?
In the brain (it cannot cross BBB)
What alpha G protein subunit results in the increased production of cAMP from adenylyl cyclase?
Gs
What G protein alpha subunit stimulation results in decreased production of cAMP from adenylyl cyclase?
Gi
What enzyme produces cAMP?
Adenylyl cyclase
What enzyme produces inositol triphosphate?
Phospholipase C (PLC)
What enzyme produces diacylglycerol?
Phospholipase C
What enzyme produces eicosanoids?
Phospholipase A2 (PLA2)
What is the precursor for cAMP?
Adenosine triphosphate (ATP)
What is the precursor for DAG and IP3?
Phosphatidylinositol 4,5-bisphosphate (PIP2)
What G protein and substance are responsible for DAG and IP3 production?
Gq
Ca++
What second messenger binds to Ca++ channels on the endoplasmic reticulum resulting in Ca++ release from ER into the cytoplasm?
IP3
What second messenger acts as a docking site for and activator of protein kinase C (PKC)?
DAG
What second messengers leave the cell and bind to GPCR on the surface of target cells?
Eicosanoids
What enzyme liberates arachidonic acid from the cell membrane?
Phospholipase A2 (PLA2)
What is the precursor for prostaglandins, thromboxanes, leukotrienes, and CYP450 monooxygenases?
Arachidonic acid
What is the precursor for endocannabinoids?
Arachidonic acid
What family of enzymes catalyze the addition of phosphate groups to their groups?
Kinases
Ion movement during direct excitatory response
Na+ into the cell
Ca++ into the cell
Ion movement during direct inhibitory response
Cl- into the cell
Signal transduction of Nm ACh receptors
Opens nonselective cation channels > Na+ influx
Signal transduction of Nn ACh receptors
Opens nonselective cation channels > Na+ influx
Location of Nm ACh receptors
Skeletal muscle at the neuromuscular junction
Location of Nn ACh receptors
Autonomic ganglia
Adrenal medulla
CNS
Response to Nm ACh receptor stimulation
End-plate depolarization and skeletal muscle contraction
Response to Nn ACh receptor stimulation
Depolarization of postsynaptic postganglionic neuron
Secretion of catecholamines
Arousal, attention, analgesia
Signal transduction pathway of M1 ACh receptor
Gq > PLC > increase IP3 & increase DAG > increase Ca++ > increase PKC
Signal transductions (2) of M2 ACh receptor
Beta/ gamma subunit of Gi > increase K+ channel (GIRK) opening
Gi > inhibits AC > decrease cAMP
Signal transduction of M3 ACh receptor
Gq > PLC > increase IP3 & increase DAG > increase Ca++ > increase PKC
Signal transductions (2) of M4 ACh receptor
Beta/ gamma subunit of Gi > increase K+ channel (GIRK) opening
Gi > inhibits AC > decrease cAMP
Signal transduction of M5 ACh receptor
Gq > PLC > increase IP3 & increase DAG > increase Ca++ > increase PKC
Locations of M1 ACh receptors
Autonomic ganglia
CNS
Locations of M2 ACh receptors
Cardiac nodal tissue
Cardiac muscle tissue
Locations of M3 ACh receptors
Smooth muscle
GI
Locations of M4 ACh receptors
CNS
Locations of M5 ACh receptors
CNS
Response to M1 ACh receptor stimulation
Autonomic- excitatory
Arousal, attention, analgesia
Response to M2 ACh receptor stimulation
Slowed spontaneous depolarization (decrease chronotropy); hyperpolarization
Decreased contractility (inotropy); Decreased Dromotropy
Response to M3 ACh receptor stimulation
Smooth muscle contraction
Increased salivary secretions
Response to M4 ACh receptor stimulation
Presynaptic autoreceptors > negative feedback to suppress ACh release
Response to M5 ACh receptor stimulation
Promotes dopamine release, dilation of cerebral arteries
Two of the main ionotropic glutamate receptors
NMDA
AMPA
How are AMPA receptors activated?
Binding of two glutamate molecules
What conditions must be met for full NMDA activation?
Binding of two glutamates
Binding of two glycine molecules
Depolarizing voltage change
Glutamate receptor that has non-selective cation channels that are highly permeable to Na+, but poorly permeable to Ca++
AMPA receptor
Glutamate receptor that has non-selective cation channels that are highly permeable to Ca++, but poorly permeable to Na+
NMDA receptor
Glutamate receptor that has Mg++ bound in the resting state
NMDA receptor
Glutamate receptor that depolarizes the postsynaptic membrane d/t glutamate release
AMPA receptor
How is the Mg++ block relieved on the NMDA receptor?
Depolarization caused by AMPA receptor activity
How is glutamate receptor activation terminated?
- Transmitter reuptake by presynaptic glial transporters
- Transmitter diffusion out of the synaptic cleft
- Receptor desensitization
What is exicitoxicity?
Neuronal injury initiated by excessive glutamate receptor activity
The majority of hypnotics target what receptor?
GABAa receptor
Pentameric ligand-gated Cl- channel
GABAa receptor
How are GABAa receptors activated?
By binding of two GABA molecules
What type of receptor are GABAb receptors?
Metabotropic
Amino acid neurotransmitter formed from serine in an enzyme-catalyzed reaction
Glycine
Glutamate is converted to GABA by what type of enzymatic reaction?
Decarboxylation
The 5 biogenic amine neurotransmitters
Dopamine
Norepinephrine
Epinephrine
Serotonin
Histamine
The 3 catecholamines
Dopamine
Norepinephrine
Epinephrine
Most biogenic amine neurotransmitter receptors are what type of receptor?
Metabotropic
What type of receptor is the 5-HT3 serotonin receptor?
Ionotropic
All catecholamines are synthesized from what amino acid?
L-tyrosine
Serotonin is synthesized from what amino acid?
Tryptophan
Histamine is synthesized from what amino acid?
Histidine
How is tyrosine generated if tyrosine supply is low?
Cells can generate tyrosine from phenylalanine by hydorxylation
What is the rate limiting step to in catecholamine synthesis?
Tyrosine hydroxylation by the enzyme tyrosine hydroxylase to form L-DOPA
What two enzymes metabolize catecholamines?
Monoamine oxidase
Catechol-O-methyltransferase (COMT)
What is the end-product of catecholamine metabolism?
Vanillylmandelic acid (VMA)
What is the major metabolite of dopamine?
Homovanillic acid (HVA)
What is the metabolite of serotonin?
5-hydroxyindoleacetic acid (5-HIAA)
What cells synthesize histamine in the periphery?
Mast cells
Basophils
What is the major metabolite of histamine?
Imidazole acetic acid
What enzymatic reaction is present in ALL biogenic amine neurotransmitter biosynthesis?
Decarboxylation
Where is the largest concentration of dopaminergic neurons in the brain?
Substantia nigra
Where is the major concentration of noradrenergic neurons in the CNS?
Locus coeruleus in the pons
Where are the two major groups of adrenergic neurons in the CNS?
Rostral ventrolateral medulla
Nucleus tractus solitarius
Describe the release of norepinephrine in the peripheral nervous system
From the postganglionic sympathetic neurons onto target tissues
Describe the release of epinephrine in the peripheral nervous system
From chromaffin cells of the adrenal medulla into the circulation in response to stress
What is the relationship between isoproterenol and alpha- and beta- adrenergic receptors?
Isoproterenol activates beta adrenergic receptors, but alpha adrenergic receptors are poorly activated by isoproterenol
Norepinephrine preferentially binds to what receptors?
Alpha 1
Alpha 2
Beta 1
Low concentrations of epinephrine has predominantly what effects?
Beta
Higher concentrations of epinephrine has predominantly what effects?
Alpha-1
Where are serotonin receptors located?
Rostral raphe nuclei > thalamus, limbic system, and cortex
Caudal raphe nuclei > spinal cord and within brainstem
Where is the highest density of histamine-containing neurons?
Turberomammillary region of the hypothalamus
D2, D3, D4 alpha subunit
Gi
Alpha-1 alpha subunit
Gq
Alpha-2 alpha subunit
Gi
Beta (1,2,3) alpha subunit
Gs
5-HT1 alpha subunit
Gi
5-HT2 alpha subunit
Gq
5-HT4 alpha subunit
Gs
Molecule composed of 5-carbon sugar (pentose), a nitrogenous base, at least one phosphate group
Nucleotide
What are the main pruinergic transmitters?
ATP, ADP, and adenosine
What does a sharp increase in adenosine levels in the extracellular fluid indicate?
Acute oxygen deficiency (stroke, MI, angina pectoris)
How are purinergic neurotransmitters metabolized?
5’-AMP
Role of P2X receptors on sensory nerves
Detecting and signaling tissue damage and inflammation
How is platelet aggregation induced?
ADP binding to P2Y receptors
What signaling complex activates nitric oxide synthase?
Ca++/ Calmodulin
The 5 types of enzyme-linked receptors
- Receptor guanyly cyclases
- Receptor tyrosine kinases
- Tyrosine kinase-associated receptors
- Receptor serine/ threonine kinases
- Receptor tyrosine phosphatases
Cytosolic, heme-containing enzyme activated by nitric oxide
Soluble guanylyl cyclase
Guanylyl cyclase ligands
Atrial natriuretic peptide (ANP)
Brain atrial natriuretic peptide (BNP)
C-type natriuretic peptide (CNP)
Group of enzyme-linked receptors that work in pairs
Receptor tyrosine kinases
Receptor tyrosine kinases’ ligands
Hormones
Growth factors
Genetically regulated cell death
Apoptosis