Term
| What are 3 basic ways to regulate receptor function? |
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Definition
1) uncoupling ligand-binding from conformational change in receptors (desensitization)
2) Uncoupling active conformation of receptor from interacting with effectors
3) Changing number of available receptors by regulating internalization of gene expression. |
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Term
| What kind of desensitization is occurring when continued application of Ach fails to maintain depolarization in skeletal muscle? |
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Definition
| Homologous Desensitization |
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Term
| What kind of desensitization is occurring when continued activation of muscurinic Ach receptors decreases the inducible activity of Adenylyl Cyclase? |
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Definition
| Heterologous Desensitization (involving second messengers) |
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Term
| How is the desensitization of nicotinic Ach receptors difference from B-adrenergic receptors? |
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Definition
1) nAch receptors are rapid, ionotropic receptors
- Desensitized fast
- Intrinsic property of the receptor
- Homologous only
- Uncouples channel function
- Modulated by phosphorylation
2) B-adrenergic receptors are GPCRs
- Desensitization is slow
- Homologous and Heterologous
- Not intrinsic
- Uncouples G protein activation
- Requires phosphorylation of the receptor. |
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Term
True:False
Receptor desensitization is partially due to decreased ligand-binding affinity? |
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Definition
False!
Desensitization involves a lack of coupling between occupancy and confirmation changes in a receptor. The ligand binds just fine. |
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Term
| How is rapid desensitization of ionotropic nicotinic Ach receptors achieved? |
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Definition
Short answer- ligand-bound by a single Ach, but still closed. This desensitization is faster with allosteric covalent regulation of the receptor by phosphorylation.
Explanation- After prolonged Ach exposure, a long-lasting conformational change occurs where the channel no long opens in response to stimulation.
Desensitization can occur without the channel opening and can be initiated by the binding of a single Ach molecule, where only the receptor shell "uncoupled" to receptor-opening is closed.
In this way, the receptor is "ligand-bound," but still cannot open. |
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Term
| What are the different mechanisms of homologous desensitization of beta-adrenergic receptors? |
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Definition
Short-term exposure to ligands
1) low ligand concentration leads to phosphorylation of receptor via PKA at the G-protein binding site.
** This same pathway can be heterologous when postaglandin E1 receptors activate AC to start the cAMP-dependent phosphorylation of B-adrenergic receptors**
2) high ligand concentration leads to activation of B-ark (specific to b-adrenergic receptor), which phosphorylates the C-terminal region of the receptor, which recruits Arrestin to block receptor associations with G proteins.
Prolonged exposure
1) Arrestin-mediated receptor internalization |
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Term
| What are the different functions of Arrestin in GPCR signaling? |
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Definition
1) Enables desensitization from short-term exposure to ligands at high ligand concentrations by inhibiting receptor-G protein interactions.
2) Enables desensitization after prolonged ligand exposure via receptor internalization (endocytosis)
3) Induction of noncanonical signaling through MAPK |
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Term
1) How is B-adrenergic activation associated with negative feedback?
2) How is nicotinic Ach receptor gene expression regulated during muscle development (i.e. denervation)? |
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Definition
1) Receptor activation decreases stability of mRNA encoding the receptor
2) Switching between adult and fetal isoforms and changing the number of nuclei expressing subunit mRNAs in syncytial muscle. |
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