Proteopedia - User contributions [en]

Mu Opioid Receptor

2018-04-30T20:14:50Z

Jamie Heet:

== Mu Opioid Receptor==
<StructureSection load='4n6h' size='340' side='right' caption='Human Delta Opioid 7TM Receptor'scene=''>
Opioid receptors are G-protein coupled receptors (GPCR), which bind endogenous opioid peptide neurotransmitters (such as enkephalins and endorphins) and exogenous synthetic opiate drugs (such as morphine, codeine, and heroin) as ligands to hinder pain-signaling in the brain, peripheral nerves, and digestive tract. μ-opioid receptors are one of the four major classes of opioid receptors, which also includes δ-opioid receptors, κ-opioid receptors, and nociceptin opioid receptors. The μ-opioid receptor MOR-1 is expressed by the gene OPRM1 in vertebrates. <ref>DOI: 10.1124/pr.112.007138</ref> MOR-1 has important implications as a target for pain relievers as well as a treatment for drug abuse.

== Structural highlights ==

The molecular structure of MOR-1 was better understood after its cloning in 1993. According to the American Society for Pharmacology and Experimental Therapeutics, the amino acid sequence of MOR-1 is 60-70% homologous to the other classes of opioid receptors. The difference between MOR-1 and the other opioid receptor proteins lies in its extracellular N-terminus, intracellular C-terminus, and second and third extracellular loops. The μ-opioid receptor is a<scene name='77/778329/7tm/1'> 7-multispanning integral membrane protein</scene> found in dorsal root ganglion cells and peripheral nerve cells in humans, with its binding site exposed to the extracellular surface. The transmembrane domain of MOR-1 will dimerize at TM5 and TM6 to form oligomers. <ref>DOI: 10.1124/pr.112.007138</ref> The active site of the receptor, where opioid molecules bind, is between TM3, TM5, TM6, and TM7. <ref>DOI: 10.1016/j.str.2011.08.003</ref>

== Function ==

MOR-1 is a G-protein coupled receptor (GPCRs), which binds extracellular signaling molecules including exogenous opiate drugs (such as morphine, codeine, and heroin) and endogenous opioid peptide neurotransmitters (such as enkephalins, endorphins, and dynorphins) as ligands to hinder pain-signaling. Endogenous opioids play a role in naturally reducing sensations of pain felt by the body. However, they do not evoke as powerful a physiological response as exogenous opioids. <ref>DOI: 10.1124/pr.112.007138</ref>

In the presence of a signaling molecule, an active G protein will have GTP bound, to promote an intracellular signaling cascade. After the G protein has transduced the signal, it exchanges GTP for GDP and becomes inactive until another signaling molecule binds to the GPCR.

In the case of the μ-opioid receptor, the binding of an opioid signaling molecule induces a conformational change in the receptor that activates an inhibitory G-protein (Gαi/o). This results in the dissociation of the G-protein complex. The Gα subunit then inhibits adenylyl cyclase. The Gβγ subunit acts to inhibit Ca2+ channels while activing K+ channels. While much has been learned about μ-opioid receptors since their discovery in 1973, there is still much that is unknown about their structure and activation mechanism. Thus, further research into this area is needed. <ref>DOI: 10.1016/j.str.2011.08.003</ref>

== Disease ==

μ-opioid receptors are the only opioid receptors that are linked with physical dependence to opioids. A study by Matthes et al. found that mice lacking μ-opioid receptors showed no physical response or dependence after being injected with morphine. They also did not observe these effects when δ-opioid receptors and κ-opioid receptors were present in the mice injected with morphine. These results suggest that only μ-opioid receptors are involved in physical response and dependence secondary to opioids. <ref>DOI: 10.1038/383819a0</ref>

== Relevance ==

According to the National Institute on Drug Abuse, 115 Americans die every day as a result of opioid overdose. Furthermore, the opioid crisis our country faces has two million Americans directly in its grips. <ref name= "Article 1" >National Institute on Drug Abuse. “Opioid Overdose Crisis.” NIDA, 6 Mar. 2018, www.drugabuse.gov/drugs-abuse/opioids/opioid-overdose-crisis. </ref>. The opioid drug class includes the controlled substances morphine, fentanyl, codeine, hydrocodone, and oxycodone as well as the illegal substance, heroin. The aforementioned drugs act at opioid receptors in the brain and provide pain relief in addition to a sense of euphoria and sedation. Exogenous opioids that result in physical dependence act specifically at μ-opioid receptors (MOR). <ref>DOI: 10.1016/j.aat.2010.12.008</ref> To wage a successful war against opioids in the United States, we must fully understand the science behind opioid addiction.

The biochemistry of opioid addiction points to the ventral tegmental area (VTA) of the brain, the reward center. In this area, there are a high concentration of μ-opioid receptors on the surfaces of neurons. When exogenous opioid agonists are present, they bind to the active site of the μ-opioid receptor. This sends a signal along the axon of the neuron to activate dopaminergic neurons. Upon activation of dopaminergic neurons, dopamine is released into the synapse and binds to post-synaptic receptors. The binding of dopamine results in feelings of euphoria. Exogenous opioids produce larger amounts of dopamine than endogenous opioids. When exogenous opioids are abused, the behavior of abusing them is reinforced by the feelings of pleasure from dopamine. Overtime, an addicted person develops a tolerance and more opioids are needed in order to release the same amount of dopamine as the first use. <ref name= "Article 2" > Contet, Candice, et al. “Mu Opioid Receptor: a Gateway to Drug Addiction.” Current Opinion in Neurobiology, 19 May 2004, pp. 370–378., doi:10.1016/s0959-4388(04)00072-8. </ref>.

</StructureSection>
== References ==
<references/>

Mu Opioid Receptor

2018-04-30T20:13:54Z

Jamie Heet: New page: == Mu Opioid Receptor== <StructureSection load='4n6h' size='340' side='right' caption='Human Delta Opioid 7TM Receptor'scene=''> Opioid receptors are G-protein coupled receptors (GPCR), ...

== Mu Opioid Receptor==
<StructureSection load='4n6h' size='340' side='right' caption='Human Delta Opioid 7TM Receptor'scene=''>

Opioid receptors are G-protein coupled receptors (GPCR), which bind endogenous opioid peptide neurotransmitters (such as enkephalins and endorphins) and exogenous synthetic opiate drugs (such as morphine, codeine, and heroin) as ligands to hinder pain-signaling in the brain, peripheral nerves, and digestive tract. μ-opioid receptors are one of the four major classes of opioid receptors, which also includes δ-opioid receptors, κ-opioid receptors, and nociceptin opioid receptors. The μ-opioid receptor MOR-1 is expressed by the gene OPRM1 in vertebrates. <ref>DOI: 10.1124/pr.112.007138</ref> MOR-1 has important implications as a target for pain relievers as well as a treatment for drug abuse.

== Structural highlights ==

The molecular structure of MOR-1 was better understood after its cloning in 1993. According to the American Society for Pharmacology and Experimental Therapeutics, the amino acid sequence of MOR-1 is 60-70% homologous to the other classes of opioid receptors. The difference between MOR-1 and the other opioid receptor proteins lies in its extracellular N-terminus, intracellular C-terminus, and second and third extracellular loops. The μ-opioid receptor is a<scene name='77/778329/7tm/1'> 7-multispanning integral membrane protein</scene> found in dorsal root ganglion cells and peripheral nerve cells in humans, with its binding site exposed to the extracellular surface. The transmembrane domain of MOR-1 will dimerize at TM5 and TM6 to form oligomers. <ref>DOI: 10.1124/pr.112.007138</ref> The active site of the receptor, where opioid molecules bind, is between TM3, TM5, TM6, and TM7. <ref>DOI: 10.1016/j.str.2011.08.003</ref>

== Function ==

MOR-1 is a G-protein coupled receptor (GPCRs), which binds extracellular signaling molecules including exogenous opiate drugs (such as morphine, codeine, and heroin) and endogenous opioid peptide neurotransmitters (such as enkephalins, endorphins, and dynorphins) as ligands to hinder pain-signaling. Endogenous opioids play a role in naturally reducing sensations of pain felt by the body. However, they do not evoke as powerful a physiological response as exogenous opioids. <ref>DOI: 10.1124/pr.112.007138</ref>

In the presence of a signaling molecule, an active G protein will have GTP bound, to promote an intracellular signaling cascade. After the G protein has transduced the signal, it exchanges GTP for GDP and becomes inactive until another signaling molecule binds to the GPCR.

In the case of the μ-opioid receptor, the binding of an opioid signaling molecule induces a conformational change in the receptor that activates an inhibitory G-protein (Gαi/o). This results in the dissociation of the G-protein complex. The Gα subunit then inhibits adenylyl cyclase. The Gβγ subunit acts to inhibit Ca2+ channels while activing K+ channels. While much has been learned about μ-opioid receptors since their discovery in 1973, there is still much that is unknown about their structure and activation mechanism. Thus, further research into this area is needed. <ref>DOI: 10.1016/j.str.2011.08.003</ref>

== Disease ==

μ-opioid receptors are the only opioid receptors that are linked with physical dependence to opioids. A study by Matthes et al. found that mice lacking μ-opioid receptors showed no physical response or dependence after being injected with morphine. They also did not observe these effects when δ-opioid receptors and κ-opioid receptors were present in the mice injected with morphine. These results suggest that only μ-opioid receptors are involved in physical response and dependence secondary to opioids. <ref>DOI: 10.1038/383819a0</ref>

== Relevance ==

According to the National Institute on Drug Abuse, 115 Americans die every day as a result of opioid overdose. Furthermore, the opioid crisis our country faces has two million Americans directly in its grips. <ref name= "Article 1" >National Institute on Drug Abuse. “Opioid Overdose Crisis.” NIDA, 6 Mar. 2018, www.drugabuse.gov/drugs-abuse/opioids/opioid-overdose-crisis. </ref>. The opioid drug class includes the controlled substances morphine, fentanyl, codeine, hydrocodone, and oxycodone as well as the illegal substance, heroin. The aforementioned drugs act at opioid receptors in the brain and provide pain relief in addition to a sense of euphoria and sedation. Exogenous opioids that result in physical dependence act specifically at μ-opioid receptors (MOR). <ref>DOI: 10.1016/j.aat.2010.12.008</ref> To wage a successful war against opioids in the United States, we must fully understand the science behind opioid addiction.

The biochemistry of opioid addiction points to the ventral tegmental area (VTA) of the brain, the reward center. In this area, there are a high concentration of μ-opioid receptors on the surfaces of neurons. When exogenous opioid agonists are present, they bind to the active site of the μ-opioid receptor. This sends a signal along the axon of the neuron to activate dopaminergic neurons. Upon activation of dopaminergic neurons, dopamine is released into the synapse and binds to post-synaptic receptors. The binding of dopamine results in feelings of euphoria. Exogenous opioids produce larger amounts of dopamine than endogenous opioids. When exogenous opioids are abused, the behavior of abusing them is reinforced by the feelings of pleasure from dopamine. Overtime, an addicted person develops a tolerance and more opioids are needed in order to release the same amount of dopamine as the first use. <ref name= "Article 2" > Contet, Candice, et al. “Mu Opioid Receptor: a Gateway to Drug Addiction.” Current Opinion in Neurobiology, 19 May 2004, pp. 370–378., doi:10.1016/s0959-4388(04)00072-8. </ref>.

</StructureSection>
== References ==
<references/>

2018-04-30T01:54:00Z

Jamie Heet:

[http://www.example.com link title]{{Sandbox_Reserved_Telford2018}}
== Mu Opioid Receptor==
<StructureSection load='4n6h' size='340' side='right' caption='Human Delta Opioid 7TM Receptor'scene=''>
This is a default text for your page ''''''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

Opioid receptors are G-protein coupled receptors (GPCR), which bind endogenous opioid peptide neurotransmitters (such as enkephalins and endorphins) and exogenous synthetic opiate drugs (such as morphine, codeine, and heroin) as ligands to hinder pain-signaling in the brain, peripheral nerves, and digestive tract. μ-opioid receptors are one of the four major classes of opioid receptors, which also includes δ-opioid receptors, κ-opioid receptors, and nociceptin opioid receptors. The μ-opioid receptor MOR-1 is expressed by the gene OPRM1 in vertebrates. MOR-1 has important implications as a target for pain relievers as well as a treatment for drug abuse.

== Structural highlights ==

The molecular structure of MOR-1 was better understood after its cloning in 1993. According to the American Society for Pharmacology and Experimental Therapeutics, the amino acid sequence of MOR-1 is 60-70% homologous to the other classes of opioid receptors. The difference between MOR-1 and the other opioid receptor proteins lies in its extracellular N-terminus, intracellular C-terminus, and second and third extracellular loops. The μ-opioid receptor is a 7-multispanning integral membrane protein found in dorsal root ganglion cells and peripheral nerve cells in humans, with its binding site exposed to the extracellular surface. The transmembrane domain of MOR-1 will dimerize at TM5 and TM6 to form oligomers. The active site of the receptor, where opioid molecules bind, is between TM3, TM5, TM6, and TM7.

== Function ==

MOR-1 is a G-protein coupled receptor (GPCRs), which binds extracellular signaling molecules including exogenous opiate drugs (such as morphine, codeine, and heroin) and endogenous opioid peptide neurotransmitters (such as enkephalins, endorphins, and dynorphins) as ligands to hinder pain-signaling. Endogenous opioids play a role in naturally reducing sensations of pain felt by the body. However, they do not evoke as powerful a physiological response as exogenous opioids.

In the presence of a signaling molecule, an active G protein will have GTP bound to it so it can initiate an intracellular signaling cascade. After the G protein has transduced the signal, it exchanges GTP for GDP and becomes inactive until another signaling molecule binds to the GPCR.

In the case of the μ-opioid receptor, the binding of an opioid signaling molecule induces a conformational change in the receptor that activates an inhibitory G-protein (Gαi/o). This results in the dissociation of the G-protein complex. The Gα subunit then inhibits adenylyl cyclase. The Gβγ subunit acts to inhibit Ca2+ channels while activing K+ channels. While much has been learned about μ-opioid receptors since their discovery in 1973, there is still much that is unknown about their structure and activation mechanism. Thus, further research into this area is needed.

== Disease ==

μ-opioid receptors are the only opioid receptors that are linked with physical dependence to opioids. A study by Matthes et al. found that mice lacking μ-opioid receptors showed no physical response or dependence after being injected with morphine. They also did not observe these effects when δ-opioid receptors and κ-opioid receptors were present in the mice injected with morphine. These results suggest that only μ-opioid receptors are involved in physical response and dependence secondary to opioids.

== Relevance ==

According to the National Institute on Drug Abuse, 115 Americans die every day as a result of opioid overdose. Furthermore, the opioid crisis our country faces has two million Americans directly in its grips. The opioid drug class includes the controlled substances morphine, fentanyl, codeine, hydrocodone, and oxycodone as well as the illegal substance, heroin. The aforementioned drugs act at opioid receptors in the brain and provide pain relief in addition to a sense of euphoria and sedation. Exogenous opioids that result in physical dependence act specifically at μ-opioid receptors (MOR). To wage a successful war against opioids in the United States, we must fully understand the science behind opioid addiction.

The biochemistry of opioid addiction points to the ventral tegmental area (VTA) of the brain, the reward center. In this area, there are a high concentration of μ-opioid receptors on the surfaces of neurons. When exogenous opioid agonists are present, they bind to the active site of the μ-opioid receptor. This sends a signal along the axon of the neuron to activate dopaminergic neurons. Upon activation of dopaminergic neurons, dopamine is released into the synapse and binds to post-synaptic receptors. The binding of dopamine results in feelings of euphoria. Exogenous opioids produce larger amounts of dopamine than endogenous opioids. When exogenous opioids are abused, the behavior of abusing them is reinforced by the feelings of pleasure from dopamine. Overtime, an addicted person develops a tolerance and more opioids are needed in order to release the same amount of dopamine as the first use.

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

Contet, Candice, et al. “Mu Opioid Receptor: a Gateway to Drug Addiction.” Current Opinion in Neurobiology, 19 May 2004, pp. 370–378., doi:10.1016/s0959-4388(04)00072-8.

Matthes, Hans W. D., et al. “Loss of Morphine-Induced Analgesia, Reward Effect and Withdrawal Symptoms in Mice Lacking the µ-Opioid-Receptor Gene.” Nature, vol. 383, no. 6603, 1996, pp. 819–823., doi:10.1038/383819a0.

National Institute on Drug Abuse. “Opioid Overdose Crisis.” NIDA, 6 Mar. 2018, www.drugabuse.gov/drugs-abuse/opioids/opioid-overdose-crisis.

Pasternak, G. W., and Y.-X. Pan. “Mu Opioids and Their Receptors: Evolution of a Concept.” Pharmacological Reviews, vol. 65, no. 4, 2013, pp. 1257–1317., doi:10.1124/pr.112.007138.

Pasternak, Gavril, and Ying-Xian Pan. “Mu Opioid Receptors in Pain Management.” Acta Anaesthesiologica Taiwanica, vol. 49, no. 1, Mar. 2011, pp. 21–25., doi:10.1016/j.aat.2010.12.008.

Serohijos, Adrian W.r., et al. “Structural Basis for μ-Opioid Receptor Binding and Activation.” Structure, vol. 19, no. 11, 9 Nov. 2011, pp. 1683–1690., doi:10.1016/j.str.2011.08.003.

2018-04-11T19:36:59Z

Jamie Heet:

Sandbox Reserved 1449

2018-04-11T19:36:02Z

Jamie Heet:

{{Sandbox_Reserved_Telford2018}}
== Delta Opioid Receptor==
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
This is a default text for your page ''''''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

here is my great <scene name='77/778329/4ej4_with_nitrosomething/1'>scene</scene>

== Function ==

== Disease ==

== Relevance ==

== Structural highlights ==

== dlfkaslkdfj ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

http://www.rcsb.org/structure/4N6H

Sandbox Reserved 1449

2018-04-11T19:34:24Z

Jamie Heet:

{{Sandbox_Reserved_Telford2018}}
==Your Heading Here (maybe something like 'Structure')==
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
This is a default text for your page ''''''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

here is my great <scene name='77/778329/4ej4_with_nitrosomething/1'>scene</scene>

== Function ==

== Disease ==

== Relevance ==

== Structural highlights ==

== dlfkaslkdfj ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

http://www.rcsb.org/structure/4N6H

2018-04-11T19:04:41Z

Jamie Heet:

{{Sandbox_Reserved_Telford2018}}
Uricase
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>

Uricase is an enzyme that catalyzes the conversion or uric acid to allantoin. Uric acid is
an acidic waste product that your body passes through urine. It is a normal byproduct of the
breakdown of foods that contain purines. Normally, the kidneys filter out uric acid from your
blood; if too much builds up, it can lower the pH of your blood and urine and lead to a painful
joint condition called gout and other complications. The reason I chose uricase is because it
monitors the uric acid levels in our body. Interestingly, humans have naturally selected to
terminate uricase. Because of the absence of uricase in humans, we may go through many
complications caused by uric acid build up. Scientists are studying why natural selection would
allow the accumulation of uric acid even though there are psychological complications of
crystalized monosodium urate acutely causing liver and kidney damage or chronically causing
gout.

== Function ==
<Structure load='4EJ4' size='350' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' />
== Disease ==

== Relevance ==

== Structural highlights ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>