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Norepinephrine (NE)
Catecholamine neurotransmitter that can activate adrenergic receptors, including β adrenergic receptors.
Epinephrine (Epi)
Catecholamine neurotransmitter and hormone that can activate adrenergic receptors.
β adrenergic receptor
Metabotropic GPCR activated by NE or epinephrine. Can activate Gs.
Gs
G protein that activates adenylyl cyclase.
Adenylyl cyclase (AC)
Enzyme that converts ATP into cAMP.
cAMP
Second messenger that activates protein kinase A.
Protein kinase A (PKA)
Protein kinase activated by cAMP. Phosphorylates target proteins.
cAMP pathway
NE or Epi -> β receptor -> Gs -> adenylyl cyclase -> cAMP -> PKA -> protein phosphorylation.
Gq
G protein that activates phospholipase C.
Phospholipase C (PLC)
Enzyme that splits PIP₂ into IP₃ and DAG.
PIP₂
Membrane phospholipid that PLC splits into IP₃ and DAG.
IP₃
Second messenger that binds receptors on the ER and causes stored Ca²⁺ to be released into the cytoplasm.
DAG
Second messenger that remains in the membrane and helps activate PKC.
Protein kinase C (PKC)
Protein kinase activated downstream of DAG and Ca²⁺. Phosphorylates target proteins.
Phosphoinositide pathway
Gq -> PLC -> PIP₂ -> IP₃ + DAG -> Ca²⁺ release -> PKC activation.
Calmodulin (CaM)
Intracellular protein that binds Ca²⁺. The Ca²⁺ and calmodulin complex can activate CaMK.
Ca²⁺/calmodulin complex
Formed when Ca²⁺ binds to calmodulin. Activates proteins including CaMK.
CaMK
Calcium/calmodulin dependent protein kinase. Activated by the Ca²⁺/calmodulin complex and phosphorylates target proteins.
CaMK pathway
Intracellular Ca²⁺ increases -> Ca²⁺ binds calmodulin -> Ca²⁺/calmodulin activates CaMK -> CaMK phosphorylates proteins.
CaMKII
Major CaMK in neurons. Important for synaptic plasticity and changes in synaptic strength.
Protein kinase
Enzyme that adds phosphate groups to proteins and changes their activity.
Protein phosphatase
Enzyme that removes phosphate groups from proteins.
Phosphorylation
Addition of a phosphate group to a protein, which can change that protein's function.
Catecholamines
Family of neurotransmitters containing dopamine, norepinephrine, and epinephrine.
Tyrosine
Amino acid used as the starting material for catecholamine synthesis.
Tyrosine hydroxylase
Enzyme converting tyrosine -> L DOPA. Rate limiting enzyme of catecholamine synthesis.
L DOPA
Precursor converted into dopamine.
DOPA decarboxylase
Enzyme converting L DOPA -> dopamine.
Dopamine (DA)
Catecholamine neurotransmitter and precursor to norepinephrine.
Dopamine β hydroxylase
Enzyme converting dopamine -> norepinephrine.
Norepinephrine (NE) (Synthesis)
Catecholamine made from dopamine and precursor to epinephrine.
PNMT
Enzyme converting norepinephrine -> epinephrine.
Catecholamine synthesis
Tyrosine -> L DOPA -> dopamine -> norepinephrine -> epinephrine.
Serotonin (5 HT)
Monoamine neurotransmitter synthesized from tryptophan.
Tryptophan
Amino acid used as the starting material for serotonin synthesis.
Tryptophan hydroxylase
Enzyme converting tryptophan -> 5 HTP. Rate limiting enzyme in serotonin synthesis.
5 HTP
Intermediate converted into serotonin.
AADC
Enzyme converting 5 HTP -> serotonin.
Serotonin synthesis
Tryptophan -> 5 HTP -> serotonin.
Glutamate
Major excitatory neurotransmitter in the CNS.
AMPA receptor
Ionotropic glutamate receptor responsible for much of fast excitatory transmission. Opening produces a depolarizing current.
NMDA receptor
Ionotropic glutamate receptor that requires glutamate binding and sufficient depolarization to remove its Mg²⁺ block. Allows Ca²⁺ and other cations through.
NMDA Mg²⁺ block
Mg²⁺ blocks the NMDA channel at negative membrane potentials. Depolarization removes the block.
Kainate receptor
Ionotropic glutamate receptor involved in excitatory transmission.
mGluR
Metabotropic glutamate receptor. GPCR that produces slower intracellular signaling.
Acetylcholine (ACh)
Neurotransmitter that acts on nicotinic and muscarinic receptors.
Nicotinic ACh receptor
Ionotropic ACh receptor. ACh binding directly opens a cation channel.
Nicotine
Agonist of nicotinic ACh receptors.
Curare
Antagonist of nicotinic ACh receptors, particularly at the neuromuscular junction.
Muscarinic ACh receptor
Metabotropic ACh receptor that signals through G proteins.
Muscarine
Agonist of muscarinic ACh receptors.
Atropine
Antagonist of muscarinic ACh receptors.
Glycine
Inhibitory neurotransmitter especially important in the spinal cord and brainstem.
Glycine receptor (GlyR)
Ionotropic Cl⁻ channel activated by glycine, producing inhibition.
Glycinergic inhibition
Glycine increases Cl⁻ conductance, making the postsynaptic neuron less likely to fire.
Ionotropic receptor
Receptor that is itself an ion channel and opens directly when neurotransmitter binds.
Metabotropic receptor
Receptor that changes cell activity through intracellular signaling rather than being an ion channel itself.
GPCR
G protein coupled receptor. Metabotropic receptor that activates a G protein.
G protein
Intracellular signaling protein that connects activated GPCRs to effectors.
Effector
Protein controlled by a G protein, such as adenylyl cyclase, PLC, or an ion channel.
First messenger
Extracellular signaling molecule, such as a neurotransmitter, that binds a receptor.
Second messenger
Intracellular signaling molecule that carries and amplifies a signal inside the cell. Examples include cAMP, IP₃, DAG, and Ca²⁺.
Membrane delimited pathway
Pathway where a G protein directly regulates a nearby membrane protein without using a diffusible second messenger.
Agonist
Molecule that binds to and activates a receptor.
Antagonist
Molecule that binds to a receptor and prevents its activation.
PKA Activation
Activated by cAMP.
PKC Activation
Activated downstream of DAG and Ca²⁺.
CaMK Activation
Activated by Ca²⁺ + calmodulin.