Neuropeptides and Their Receptors Quiz

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Questions and Answers

What characterizes the majority of neuropeptide receptors?

They are primarily ionotropic receptors.

They are exclusively found in the gastrointestinal tract.

They are mediated through G protein-coupled receptors. (correct)

They directly activate ligand-gated ion channels.

What is the primary function of Substance P in the central nervous system?

Mediates synaptic inhibition.

Regulates memory consolidation in the hippocampus.

Conveys information about pain and temperature. (correct)

Acts as an excitatory neurotransmitter for muscle contractions.

Which of the following best describes the process of converting pre-propeptides into active neuropeptides?

Only occurs in the axon terminal.

Resembles transcription factors binding to DNA.

Directly synthesized in the synaptic cleft.

Involves several modifications in the Golgi apparatus. (correct)

What distinguishes endocannabinoids from conventional neurotransmitters?

They are produced in postsynaptic neurons and act on cannabinoid receptors. Signup and view all the answers

Which category do the majority of opioid peptides fall into based on their function?

Compounds that mimic the actions of morphine. Signup and view all the answers

What role do GABAergic neurotransmitters play in relation to cannabinoids?

They inhibit GABA release due to cannabinoid receptor activation. Signup and view all the answers

What is a common characteristic of the five categories of neuropeptides?

They serve distinct physiological functions in the body. Signup and view all the answers

What is the primary action of fentanyl as an opioid peptide?

It selectively stimulates opioid receptors with high potency. Signup and view all the answers

What is the primary function of G-protein-coupled receptors in neurotransmission?

Activate effector systems through G-proteins Signup and view all the answers

Which secondary messenger is specifically mentioned as being involved in excitation by NMDA receptors?

Ca2+ Signup and view all the answers

How do muscarinic acetylcholine receptors primarily differ from nicotinic receptors?

Nicotinic receptors are classified as ionotropic channels Signup and view all the answers

What is the role of G-proteins in G-protein-coupled receptor signaling?

They undergo a conformational change and activate effector proteins Signup and view all the answers

What type of glutamate receptor requires both glutamate and a postsynaptic depolarization to open?

NMDA receptor Signup and view all the answers

In cholinergic neurons, what is the impact of ACh binding to muscarinic receptors in the hippocampus?

Activation of excitatory synaptic transmission Signup and view all the answers

Which neurotransmitter plays a critical role in the plasticity and information storage of synapses?

Glutamate Signup and view all the answers

Which GABA receptor is known to be ionotropic and primarily allows the influx of Cl-?

GABAA Signup and view all the answers

What physiological effects does norepinephrine influence?

Arousal, attention, and sleep Signup and view all the answers

What is the primary function of the AMPA receptor?

Mediate fast excitatory post-synaptic responses Signup and view all the answers

Which neurotransmitter is synthesized from tryptophan and regulates mood and sleep?

Serotonin Signup and view all the answers

What role do second messenger cascades play in G-protein-coupled receptor signaling?

Amplify the signaling response Signup and view all the answers

What is the unique feature of NMDA receptors compared to other glutamate receptors?

They allow for calcium ion entry Signup and view all the answers

Which statement is true about the effects of ATP in neurotransmission?

It serves as a co-transmitter and is excitatory Signup and view all the answers

Study Notes

Neurotransmitters

Three classes of neurotransmitters: amino acids, amines, and peptides.
Neurotransmitter systems: defined by the molecule, synthetic machinery, packaging, reuptake and degradation, etc.
Acetylcholine (Ach): First identified neurotransmitter.

Studying Neurotransmitter Systems

Neurotransmitter criteria: Synthesis and storage in presynaptic neuron, released by presynaptic axon terminal, produces response in postsynaptic cell mimicking the response produced by the release of neurotransmitter from the presynaptic neuron.

Transmitter-Gated Channels

Fast synaptic transmission, sensitive detectors of chemicals and voltage.
Regulate flow of large currents.
Differentiate between similar ions.
Sensitive to specific neurotransmitter binding.

G-Protein-Coupled Receptors

Three steps: Binding of neurotransmitter to receptor protein, activation of G-proteins, activation of effector systems.
Basic Structure of G-Protein-Coupled Receptors (GPCRs): Single polypeptide with seven membrane-spanning alpha-helices.
Ubiquitous G-Proteins: GTP-binding (G-) protein, signals from receptor to effector proteins.
Five steps in G-protein operation: Inactive: Three subunits - a, b, and g - “float” in membrane (a bound to GDP), Active: Bumps into activated receptor and exchanges GDP for GTP, Ga-GTP and Gbg - Influence effector proteins, Ga inactivates by slowly converting GTP to GDP, Gbg recombine with Ga-GDP.
GPCR Effector Systems:
- Shortcut Pathway: From receptor to G-protein to ion channel, fast and local
- Second Messenger Cascades: G-protein couples neurotransmitter with downstream enzyme activation, slower in action.

Neurotransmitter Chemistry: Cholinergic (Ach) Neurons

Basal Forebrain: Nucleus basalis, medial septal nucleus, nucleus of diagonal band.
- Project to hippocampus, amygdala and cerebral cortex.
- Learning and memory.
- Loss leads to Alzheimer's disease
Pedunculopontine nucleus and laterodorsal tegmental nucleus: Project to reticular formation and thalamus.
- Arousal and sleep/wake cycle.

Nicotinic Ach Receptor

Non-selective ionotropic cation channels that generate excitatory post synaptic responses.
Needs two Ach molecules to bind to function.
Can bind nicotine (euphoria, relaxation, addiction).
Snake venom (ɑ-bungarotoxin) binds and closes channel, leading to paralysis (in muscles).
Receptor has five subunits, each with large extracellular region and four membrane spanning domains.
Opening of channel leads to Ach effects (skeleton muscle contraction, fine-tuning of neuron function in the CNS, leading to attention and arousal).

Muscarinic Ach Receptors

Muscarine (poisonous alkaloid found in some mushrooms).
Metabotropic receptor.
Mediates most effects of Ach in brain, only one Ach needed to bind.
Found in corpus striatum where they activate K+ channels to exert inhibitory influence on dopamine mediated motor effects.
Found in hippocampus where they close K+ channels and can lead to excitatory synaptic transmission.
Mediate peripheral cholinergic responses of autonomic effector organs (heart, smooth muscle, exocrine glands): Inhibit heart rate by vagus nerve innervation.
mAChR blockers useful clinically: Atropine - Used to dilate pupil, Scopolamine - Prevents motion sickness, Ipratropium - Useful in asthma

Glutamate

Most important transmitter for normal brain function: Nearly all excitatory neurons in CNS are glutamatergic.
More than half of all brain synapses release glutamate.
Precursor is glutamine, taken up by System A transporter 2.
Glutaminase key enzyme.
Removed from synapse by Excitatory Amino Acid Transporters.
Glutamate-Glutamine Cycle with Glial Cells.

AMPA Receptor

Ionotropic glutamate receptor cation channel.
ɑ-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate.
Allows passage of Na+ and K+.
Produces excitatory postsynaptic responses, EPSCs are larger and faster than other glutamate receptors.
Tetramer.

NMDA Receptor

Ionotropic glutamate receptor.
Unique pore allows Na+, K+, AND Ca2+ entry.
Excitatory postsynaptic potentials increases Ca2+ (which can act as a secondary messenger).
Mg2+ blocks the pore when cell is hyperpolarized: Imparts unique voltage dependence to current flow, removal of Mg2+ removes this behavior.
Pass cations only when postsynaptic membrane potential is depolarized (need both glutamate and postsynaptic depolarization to open): May represent some form of synaptic information storage and synaptic plasticity.
Also requires co-agonist glycine for gating.

Metabotropic Glutamate Receptors

Three classes of exist.
Can lower postsynaptic responses that can excite or inhibit postsynaptic cells.
Many lead to inhibition of postsynaptic Ca2+ and Na+ channels.

GABA

Inhibitory neurotransmission.
ˠ-aminobutyric acid.
One third of synapses use GABA.
Most found in local circuit interneurons as well as in the striatum, and cerebellar Purkinje cells.
Glucose converted to glutamate (TCA cycle), glutamate converted to GABA via glutamic acid decarboxylase: Need pyridoxal phosphate for synthesis, comes from vitamin B6.
Transported into vesicles via vesicular inhibitory amino acid transporter (VIAAT).
Removal involves Na+ dependent co transporters and breakdown in glial or neurons to succinate.

GABA Receptors

GABAA: Ionotropic anion channel (mainly Cl-), Pentamer: 19 subunit types, pore is lined with positive charged amino acids.
- Benzodiazepines (Valium; anxiety) enhance opening of channel.
- Hypnotics (Ambien; sleep) enhance opening of channel.
- Barbiturates (pentobarbital; anesthesia and epilepsy) enhance opening of channel.
- Ethanol binds and alters ionotropic GABA receptor activity.
GABAB: Metabotropic and inhibitory, Activates K+ channels, Blocks Ca2+ channels

Glycine

Half of inhibitory synapses in spinal cord.
Synthesized from serine by serine hydroxymethyltransferase.
Transported into vesicles via vesicular inhibitory amino acid transporter (VIAAT).
Removed from synapse by glycine transporters.

Ionotropic Glycine Receptors

Pentamer.
Ligand gated Cl- channels.
Influx of Cl- inhibits postsynaptic neuron.
Blocked by strychnine (toxic alkaloid chemical in some plants).

Biogenic Amines: Catecholaminergic Neurons

Dopamine

Mesostriatal Pathway: Substantia nigra-striatum (putamen and caudate nucleus)
- Coordination of body movements.
- Defective in substantia nigra in Parkinson’s disease (leads to motor dysfunction).
Mesolimbocortical Pathway: Ventral Tegmental Area-amygdala, nucleus accumbens, cortex, hippocampus (Rewards Pathway)
- Motivation, reward, reinforcement.
Produced by DOPA decarboxylase from DOPA.
Loaded into vesicles via vesicular monoamine transporter (VMAT).
Terminated by reuptake in neuron or glia via Na+ dependent dopamine co-transporter (DAT)
- Cocaine and amphetamines inhibit.
Monoamine oxidase (MAO) and catechol O-methyltransferase (COMT) break down dopamine.
Activates metabotropic Dopamine receptors, act by either activating or inhibiting adenylyl cyclase.

Norepinephrine

Noradrenaline.
Synthesized within locus coeruleus (brainstem), project to cerebral cortex, thalamus, pons, cerebellum, and spinal cord.
Influences mood, sleep, wakefulness, arousal, attention, feeding, and sexual behavior.
Requires dopamine β hydroxylase, produces norepinephrine from dopamine.
Loaded into vesicles via VMAT.
Cleared by norepinephrine transporter (NET).
Degraded by MAO and COMT.
Acts on ɑ and β adrenergic receptors: G protein coupled receptors.

Epinephrine

Adrenaline.
Found at lower levels than other catecholamines.
Lateral tegmental system and in medulla (project to thalamus and hypothalamus).
Regulate respiration and cardiac function.
Produced by Phenylethanolamine-N-methyltransferase.
Loaded into vesicles by VMAT.
Acts on ɑ and β adrenergic receptors.

Histamine

Found in hypothalamic connections to all regions of brain and spinal cord, tuberomammillary nucleus of hypothalamus.
Mediates arousal and attention, controls reactivity of the vestibular system.
May influence brain blood flow.
Produced from histidine via histidine decarboxylase.
Transported into vesicles via VMAT.
Can be taken up by monoamine transporter.
Degraded by histamine methyltransferase and MAO.
Four histamine receptors, all metabotropic, many antagonists exist (basis of antihistamine agents (Benadryl)).

Serotonin

5-hydroxytryptamine (5-HT).
Pons and upper brainstem with projections to forebrain, Raphe nuclei (brainstem)-cortex, thalamus, hypothalamus, cerebellum.
Regulate anxiety, mood, sleep, and wakefulness, target for numerous antipsychotic drugs (depression and anxiety).
Synthesized from tryptophan (tryptophan-5-hydroxylase).
Loaded into vesicles by VMAT.
Signaling terminated by Specific Serotonin Transporter (SERT), target of many SSRIs (Prozac, Fluoxetine, Zoloft).
Degraded by MAO.

5HT Receptors

Most are metabotropic: Implicated in regulation of circadian rhythms, motor behaviors, emotional states, and mental arousal, impairments implicated in depression, anxiety disorders, schizophrenia.
LSD (lysergic acid diethylamide) causes hallucinations by activation of receptors.
Also mediate satiety and decreased food consumption, which is why certain serotonergic drugs are useful in eating disorders.
One group (5-HT3) are ligand gated ion channels: nonselective cation channel (excitatory PSP), targets for Kytril and Zofran (used to prevent postoperative nausea).

ATP and Purines

ATP found in all synaptic vesicles: Co-transmitter.
Excitatory in motor neurons of spinal cord, sensory and autonomic ganglia, possibly in hippocampus.
Ionotropic purinergic receptors: P2X receptors, nonselective cation channel, excitatory PSPs, mechanosensation and pain.
Metabotropic purinergic receptors: A2A adenosine target of caffeine (antagonist), may be responsible for stimulant effects of coffee.

Neuropeptides

Hormones that act as neurotransmitters.
Pre-propeptides first formed in soma ER.
Signal sequence removed to form propeptide.
Moves to Golgi and packaged into vesicle, further modifications (cleavage, glycosylation, phosphorylation, disulfide bond formation).
Grouped into five categories: Brain-Gut peptides, Opioid peptides, Pituitary peptides, Hypothalamic releasing hormones, ‘All Other’ Peptides.
Virtually all receptors mediated through G protein coupled receptor.

Substance P

Brain Gut Peptide.
Hypotensive agent.
11 amino acid peptide.
Hippocampus, neocortex, and gastrointestinal tract, conveys information about pain and temperature.
Spinal Cord: Sensory neurotransmitter, inhibited by opioid peptides (pain suppression).

Opioid Peptides

Bind to the same postsynaptic receptors activated by opium (analgesic), one opium poppy main ingredient is morphine.
Discovered in 1970s when looking for endorphins (endogenous compounds mimicking actions of morphine).
More than 20 opioid peptides discovered in three classes: Endorphins, Enkephalins, Dynorphins.
Depressants in the CNS.
Most likely involved in sexual attraction, aggressive and submissive behaviors.
May be involved in psychiatric disorders (schizophrenia and autism).
Fentanyl: Selective agonist of opioid receptors, 80X analgesic potency of morphine.

Endocannabinoids

Unconventional Neurotransmitter.
Interact with cannabinoid receptors, target of Δ9-tetrahydrocannabinol.
Unsaturated fatty acids.
Produced in post synaptic neurons through rise in Ca2+.
Terminated by carrier mediated transport back to postsynaptic neuron.
Hydrolyzed by fatty acid hydrolase.
CB1 Receptors: Metabotropic receptor, synaptic regulation in hippocampus and cerebellum, inhibit GABA release from presynaptic membrane.

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Test your knowledge on neuropeptides and their receptors with this quiz. Explore the functions of Substance P, the conversion of pre-propeptides, and the differentiation of endocannabinoids from traditional neurotransmitters. Perfect for students of neuroscience.