Podcast
Questions and Answers
What is the structural feature that gives pentameric superfamily receptors their name?
What is the structural feature that gives pentameric superfamily receptors their name?
- Pore opening
- TMD helices
- Cys-cys looping (correct)
- Charged residues
Which drug acts as a competitive antagonist of most GABAAR's?
Which drug acts as a competitive antagonist of most GABAAR's?
- Barbiturates
- Allosteric modulator
- Bicuculline (correct)
- Benzodiazepines
Which drug enhances the actions of GABA and known to be more selective?
Which drug enhances the actions of GABA and known to be more selective?
- Bicuculline
- Barbiturates
- Allosteric modulator
- Benzodiazepines (correct)
Which drug can act alone or enhance the actions of GABA and is less selective, making it more dangerous?
Which drug can act alone or enhance the actions of GABA and is less selective, making it more dangerous?
Which subunits are selective for benzodiazepines in GABAAR receptors?
Which subunits are selective for benzodiazepines in GABAAR receptors?
Which drug acts on all GABAA receptors?
Which drug acts on all GABAA receptors?
What effect is mediated by the α2 subunit of GABAAR receptors when benzodiazepines are present?
What effect is mediated by the α2 subunit of GABAAR receptors when benzodiazepines are present?
How can the effects of benzodiazepines be eliminated?
How can the effects of benzodiazepines be eliminated?
Which drug binds to the TM domain of GABA receptors and enhances GABA?
Which drug binds to the TM domain of GABA receptors and enhances GABA?
Which drug directly stimulates GABA receptors at high concentrations?
Which drug directly stimulates GABA receptors at high concentrations?
Which drug alters the pore conformation of M2 in GABA receptors?
Which drug alters the pore conformation of M2 in GABA receptors?
Which drug is an allosteric enhancer of GlyRs?
Which drug is an allosteric enhancer of GlyRs?
Which drug is an antagonist of 5HT3R?
Which drug is an antagonist of 5HT3R?
Which drug is used to treat IBS?
Which drug is used to treat IBS?
Which type of receptors are voltage dependent and can be blocked by Mg2+?
Which type of receptors are voltage dependent and can be blocked by Mg2+?
What is the role of glycine in NMDA-R activation?
What is the role of glycine in NMDA-R activation?
What is the structure of excitatory GluR's?
What is the structure of excitatory GluR's?
Which molecules act as agonists on GluR's?
Which molecules act as agonists on GluR's?
Which type of receptors have increased selectivity for their respective receptors due to increased rigidity?
Which type of receptors have increased selectivity for their respective receptors due to increased rigidity?
Which binding site on AMPA-R's is responsible for uncompetitive antagonists?
Which binding site on AMPA-R's is responsible for uncompetitive antagonists?
Which part of GluR's structure contains the selectivity filter on the pore?
Which part of GluR's structure contains the selectivity filter on the pore?
What confers selectivity in the M2 helices of the structure?
What confers selectivity in the M2 helices of the structure?
What happens to the α-helices when the pore is closed?
What happens to the α-helices when the pore is closed?
What occurs to the helices when the pore opens?
What occurs to the helices when the pore opens?
Study Notes
Structural Features and Drug Interactions
- Pentameric superfamily receptors are characterized by their five subunit structure, which forms a central pore.
- Competitive antagonists of most GABA(A) receptors include Flumazenil, which reverses the effects of benzodiazepines.
- The drug Clonazepam enhances the actions of GABA and has a higher selectivity for specific receptors.
- Alcohol can act alone or enhance GABA’s actions but is less selective, increasing the risk of misuse and dangerous side effects.
GABA(A) Receptor Specifics
- Benzodiazepines selectively interact with the α1, α2, α3, and α5 subunits of GABA(A) receptors.
- Diazepam acts on all GABA(A) receptors, making it a broad-spectrum anxiolytic.
- The α2 subunit of GABA(A) receptors mediates anxiolytic effects when benzodiazepines are present.
- Effects of benzodiazepines can be eliminated using Flumazenil, a specific antagonist for benzodiazepine binding sites.
GABA and Its Enhancers
- The drug Thiopental binds to the transmembrane (TM) domain of GABA receptors and enhances GABA activity.
- High concentrations of Propofol directly stimulate GABA receptors.
- The drug Etomidate alters the pore conformation of the M2 segment in GABA receptors.
- The allosteric enhancer, Strychnine, enhances Glycine receptors (GlyRs).
Receptor Types and Their Mechanisms
- 5HT3R antagonists include Ondansetron, used to treat nausea.
- Linaclotide is specifically indicated for treating Irritable Bowel Syndrome (IBS).
- Voltage-dependent receptors can be blocked by Mg²⁺ ions, impacting their excitability.
NMDA and Excitatory Receptors
- Glycine acts as a co-agonist for NMDA receptor (NMDA-R) activation, necessary for channel opening.
- Excitatory Glutamate receptors (GluRs) consist of tetrameric structures with four subunits.
- Natural agonists for GluRs include glutamate and aspartate.
- Rigid receptor structures lead to increased selectivity for their respective ligands, enhancing pharmacological precision.
AMPA Receptor Structural Insights
- The GluR subunits contain a binding site for uncompetitive antagonists, specifically at the AMPA receptors (AMPA-R).
- The selectivity filter within the pore region of GluRs is located at the M2 helices.
- Selectivity in M2 helices is conferred by specific amino acids present in the sequence.
- Upon closure of the pore, the α-helices bend inward, maintaining structural integrity.
- When the pore opens, the helices undergo a conformational change, allowing ion flow and receptor activation.
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Description
Test your knowledge on pentameric superfamily receptors and excitatory ionotropic glutamate receptors with this quiz. Identify various receptors and their functions, including nAChR, 5-HT3 R, GlyR, GABAAR, AMPA, NMDA, Kainate, and ATP receptors. Explore the effects of endogenous ligands on ion channels.
