Lecture 5: Chemical Signaling by Neurotransmitters and Hormones Flashcards
Describe the structure of chemical synapses and their possible locations on a neuron.
List and provide examples of the various classes of neurotransmitters along with their respective mechanisms of synthesis and inactivation.
Discuss the processes involved in neurotransmitter release and recycling.
Describe the locations and functions of neurotransmitters outside of the central nervous system.
Describe the differences between ionotropic and metabotropic receptors with respect to their structure and signaling mechanisms.
Define allosteric modulation of neurotransmitter receptors and explain why allosteric modulators are sometimes preferable to receptor agonists or antagonists in treating neuropsychiatric disorders.
Describe the major second-messenger systems used in neurotransmission, including the identity of each second messenger and its respective protein kinase.
Define synaptic plasticity and describe the various forms of plasticity that have been identified.
Explain the similarities and differences between hormones and neurotransmitters.
List the major endocrine glands and their associated hormones.
Describe the central vasopressin and oxytocin systems and their roles in regulating social behaviour in animals.
Discuss the symptoms of autism spectrum disorder, the basis for hypothesizing that oxytocin could be used therapeutically to treat this disorder, and the status of clinical oxytocin research.
What is synaptic transmission?
Communication between neurons occurs at synapses via chemical neurotransmitters that cross the synaptic cleft.
Describe traits of transmission.
Transmission is one-way, from presynaptic cell to postsynaptic cell.
What are synaptic vesicles?
in the pre-synaptic neuron contain neurotransmitters.
What are the types of synapses?
Axodendritic – axon to dendrite
Axosomatic – axon to cell body
Axoaxonic – axon to axon
Neuromuscular junction – axon to muscle
What are electrical synapses?
electric current flows along specialized proteins
What are mixed synapses?
both chemical and electrical transmission
How many chemicals have been identified as neurotransmitters?
100
Where are neurotransmitters manufactured? And what does that mean?
In presynaptic cells, which also have a way to inactivate them.
Where are receptors for neurotransmitters located? And what do they do?
Receptors for the chemical are located on the postsynaptic cell and mediate the response of that cell.
What are the requirements to be classified as a neurotransmitter?
- Synthesis and Storage
- Release
- Receptor Binding
- Inactivation Mechanism
- Consistent Effect
Describe synthesis and storage for neurotransmitters.
The substance must be synthesized within the neuron and stored in vesicles at the nerve terminal
Describe release for neurotransmitters
Upon stimulation, the substance should be released from the presynaptic neuron.
Describe receptor binding for neurotransmitters
Must bind to specific receptors on the postsynaptic cell (except autoreceptors) to produce a response.
This interaction should lead to a physiological effect, such as altering the postsynaptic cell’s electrical activity or influencing other cellular functions.
Describe inactivation mechanisms for neurotransmitters
There must be a mechanism to inactivate
Enzymatic degradation: enzymes break down the neurotransmitter.
Reuptake: neurotransmitter molecules are reabsorbed by the presynaptic neuron.
Diffusion: the neurotransmitter diffuses away from the synaptic cleft.
Describe consistent effects for neurotransmitters
When the substance is experimentally applied to the synapse, it should mimic the effect of endogenous release and consistently produce the same effects on the postsynaptic cell.
What are some chemical substances encompassed by neurotransmitters?
Amino acids and monoamines
Acetylcholine (ACh)
ATP and adenosine
Neuropeptides, lipids, and gases
(Some neurons produce more than one type of neurotransmitter.)
How are neuropeptides different to other transmitters?
Neuropeptides Are Synthesized by a Different Mechanism Than Other Transmitters
How are most transmitters synthesized?
In the axon terminals.
How are neuropeptides synthesized?
From precursor proteins that are synthesized in the cell body and shipped to the axon terminals.
What is the speed of replenishment of neuropeptides?
Slower than for small-molecule transmitters.
What are neuromodulators?
Chemicals That Do Not Act Like Typical Neurotransmitters
What do neuromodulators do?
Altar the action of standard neurotransmitters, diffuse away from the site of release to influence more distant cells called volume transmission (Some transmitters may act in both ways)
What does Classical Transmitter Release Involve?
Exocytosis and Recycling of Synaptic Vesicles
What is transmitter release triggered by?
Ca2+ influx at membrane depolarization.
What does Ca2+ do in vesicles?
Ca2+ mediates release of transmitter from vesicles by exocytosis.
Where are transmitters released?
Only at active zones.
What is critical in vesicles for docking and how are they recycled?
Several proteins are critical in vesicle docking and exocytosis.
Vesicles are recycled by endocytosis.
What are the three models of vesicle recycling?
Clathrin-mediated endocytosis
Ultrafast endocytosis
Kiss-and-run
What is bulk endocytosis?
Recycles large amounts of vesicle membrane during high rates of neuronal activity.
What several mechanisms control the rate of neurotransmitter release by nerve cells?
Rate of cell firing.
Probability of transmitter release – synapses vary in the probability that vesicles will undergo exocytosis.
Presence of autoreceptors.
What are the mechanisms of neurotransmitter inactivation?
Enzymatic breakdown within or near the synaptic cleft.
Removal from synaptic cleft by transporter proteins on the axon terminal membrane (reuptake).
Uptake by postsynaptic cell or glial cells.
What are receptors?
Receptors are proteins on plasma membranes of a neuron, muscle cell, or secretory cell.
What do transmitters do with receptors?
Transmitters bind to specific sites on receptors, which produces a response in the receiving cell.
What are the possible effects of receptor activation?
excitatory or inhibitory
What are receptor subtypes?
Different varieties of receptors for the same neurotransmitter.
What are Ionotropic Receptors?
Consist of Multiple Subunits That Together Form an Ion Channel
What is the Resting state of an ionotropic receptor?
ion channel closed
What opens an ionotropic receptor channel?
Neurotransmitter binding
What closes an ionotropic receptor channel?
When transmitter dissociates.
How fast are ionotropic receptor channels and what is their selectivity?
Receptor channels act rapidly and are selective for specific ions, such as Na+, Ca2+, and Cl–
What can happen to ionotropic receptor channels if used to frequently?
Can undergo desensitization.
What do metabotropic receptors Consist of?
a single subunit that works by activating G proteins
What are the effects of metabotropic receptors?
Act slower but response lasts longer.
How are metabotropic receptors activated?
Activate G proteins when transmitter binds.
What do G proteins do to enzymes?
G proteins open ion channels, or stimulate or inhibit membrane effector enzymes.
What are effector enzymes involved in?
synthesis or breakdown of second messengers.
What do second messengers activate?
protein kinases that phosphorylate another protein molecule.
What do the added phosphate groups do and what do they include?
alter functioning of the protein Includes cAMP, gAMP, Ca2+, and phosphoinositide.
What are cAMP and cGMP inactivated by?
phosphodiesterases (PDEs)
What might Inhibitors of specific PDEs be useful for?
in treating various CNS disorders.
What does the phosphoinositide second-messenger system do?
breaks down a phospholipid in the cell membrane to form two second messengers: diacylglycerol (DAG) and inositol trisphosphate (IP3).
What do DAG and IP3 cause?
Increased Ca2+ that activates protein kinase C (PKC). Ca2+ also activates calcium/calmodulin kinase II (CaMKII).
What are the additional binding sites of metabotropic receptors?
allosteric sites
What do allosteric modulators do?
bind to allosteric sites and modify (positively or negatively) the effects of an agonist.
What do allosteric modulators have potential for?
treating psychiatric and neurological disorders.
What do Tyrosine Kinase Receptors do?
Mediate the action of neurotrophic factors.
What do neurotrophic factors stimulate?
survival and growth of neurons during early development and are involved in neuronal signaling.
What do Tyrosine Kinase Receptor systems generally participate in?
Regulation of long-term changes in gene expression and neuronal functioning.
What do drugs that can alter all aspects of synaptic transmission do?
Increase or decrease transmitter synthesis and block transmitter breakdown or inhibit reuptake.
What do autoreceptor agonist and antagonists do?
Autoreceptor agonists reduce transmitter release, autoreceptor antagonists enhance release by mimicing or inhibiting transmitter’s effect on receptors.
What are structural changes associated with synaptic plasticity?
loss of synapses or growth of new ones, change in dendritic length, branching, or spine density.
What are functional changes associated with synaptic plasticity?
strength of existing synapses.
What can neurons do with their dendrites?
Neurons can rapidly change the size and shape of dendritic spines, grow new spines, and/or lose existing ones. (Many abused drugs produce changes in neuron dendrites)
What are Hormones?
secreted by endocrine glands; circulate in the bloodstream.
What do target cells have?
hormone-specific receptors
What can the same substance do?
sometimes acts as both a neurotransmitter and a hormone.
What are the respective hormones from the Adrenal glands?
Adrenal medulla secretes epinephrine (EPI) and norepinephrine (NE) (monoamines).
Adrenal cortex secretes glucocorticoids (steroid hormones).
What are the respective hormones from the Gonads?
Ovaries secrete estrogens and progesterone.
Testes secrete androgens (e.g., testosterone).
What does the Islets of Langerhans in the pancreas do?
secretes insulin and glucagon (peptide hormones) – regulation of glucose.
What does the Thyroid gland do?
secretes thyroxine (T4) and triiodothyronine (T3) – regulate energy metabolism.
What does the Pineal gland do?
secretes melatonin – control of sleep and other rhythms.
What does the Pituitary gland do?
secretes hormones that control other glands.
What does the Anterior pituitary do?
secretes stimulation hormones: TSH, ACTH, FSH, LH, GH, and PRL.
What does the hypothalamus do?
Secretes releasing hormones to trigger secretion of stimulating hormones by the anterior pituitary.
What is the cause of the endocrine working slowly compared to other systems?
Because this control system consists of multiple layers, the endocrine system works more slowly than chemical communication by neurotransmitters.
What is the process of hypothalamic releasing hormones?
1.released by neurons in the median eminence.
2.Blood vessels in pituary stalk carry them to the anterior pituitary.
What hormones stimulate each other?
Thyrotropin-releasing hormone (TRH) stimulates TSH, corticotropin-releasing hormone (CRH) stimulates ACTH, gonadotropin-releasing hormone (GnRH) stimulates FSH and LH.
What are Mechanisms of Hormone Action?
Most peptide hormones act through membrane metabotropic receptors.
Insulin uses tyrosine kinase receptors.
Steroid and thyroid hormones operate mostly through intracellular receptors in the cell nucleus; function as transcription factors.
Why is The Endocrine System Important to Pharmacologists?
Drugs can adversely alter endocrine function.
Hormones may alter behavioral responses to drugs.
Hormones sometimes have psychoactive properties.
Because pituitary hormones are controlled by neurotransmitters in the brain, the endocrine system can tell us if a neurotransmitter system has been altered.
What is an example of the importance of the endocrine system?
Hormone Prolactin is inhibited by DA acting on D2 receptors expressed in the pituitary gland
DA comes from neurons at the base of the hypothalamus
Drugs used to treat schizophrenia are D2 antagonists (blocks D2 receptors)
Results in elevated prolactin levels in blood
Therefore, circulating prolactin can be used as a biomarker for D2 receptor occupancy
Negative effects of to high prolactin, e.g. mood disturbances
What is a definition of the Adrenal gland in the endocrine system?
Found over the kidney
Derived from nervous system tissue
Receives preganglionic fibers of the sympathetic nervous system
Chromaffin cells – secrete epinephrine and norepinephrine
Fight or flight
Stimulate glucose release from the liver
Glucocorticoids – cortisol in humans, (steroids)
Maintain glucose balance
What is a definition of gonads (ovaries and testes) in the endocrine system?
Estrogen, progestins
Androgens (testosterone)
Determine physical differences
Can also act on the brain
What is a definition of the pituitary gland in the endocrine system?
Secretes several hormones
Eamples include Thyroid stimulating hormone, adremocortictropic hormone, growth hormone
Also connects to the hypothalamus
Releases hypothalamic releasing hormones
Why is the endocrine system important in neuropharmacology?
Therapeutic and absued drugs alter secretion of hormones (Alcoholism leads to decrease testosterone)
Hormones alter sensitivity to drugs (Estogen and responses to drugs of abuse)
Secretion of pituitarty hormones is controlled by neurotransmitters, ‘window to the brain’
(Are particular NTs altered in disease/injury)
What is a definition of Allosteric modulators?
Both types of receptors can be affected by allosteric modulators
Both types of receptors contain additional binding sites, allosteric sites
Drugs that bind, alter the function, allosteric modulators
Can be positive or negative
Only work in the presence of agonist, not alone.
Important target in neuro disorders, allows for grater subtype specificity
Define transmitter and peptide differences?
