View source for Tutorial:The opioid receptor, a molecular switch

[[Image:Receptor.gif|frame|200|Conceptual model of the opioid receptor. Parts of the receptor between the two cardboard pieces are integrated in the cell membrane, with other parts sticking out and reaching into the cell]]
The '''opioid receptor''', a protein on the surface of nerve cells, binds to opioids such as morphine, oxicodone, heroin, and fentanyl, leading to the inability to feel pain. Repeated intake of opioids changes the response to these molecules, and can lead to addiction. 

== About this page ==
This article explains, at a level appropriate to high school students or beginning college students, how the opioid receptor is switched on and off, and what happens inside the brain as a consequence. Five student-made videos accompany this article, and are referenced below. Other pages related to this topic, typically using more technical terms and assuming some prior knowledge in biochemistry, are:
* [[Opioids]]
* [[Opioid receptor]]
* [[G protein-coupled receptor]]
* [[Mu Opioid Receptor Bound to a Morphinan Antagonist]]

== Relevance ==
When we want to turn on the lights in a dark room, we don't have to climb up a ladder to screw in a light bulb. All we have to do is flip a switch. A biological cell has switches, too, called receptors. Most are on the cell surface with a part sticking out, ready to bind to a signaling molecule. Another part of the receptor reaches into the inside of the cell, transmitting the signal. The opioid receptor can be switched on to relieve pain, for example during surgery. Tragically, it is very easy to become physically dependent on the signaling molecules. The ongoing opioid crisis in the USA shows how addictive opioids are (e.g. morphine, oxicodone, heroin, and fentanyl), with overdose deaths decreasing average life expectancy across the US population significantly.

== Natural Function ==
[[Opioid receptor|Opioid receptors]] are proteins found in neurons, the cells that allow us to think, to observe our surroundings with our senses and to move our muscles. Like all cells, neurons have a water-insoluble structure called membrane (or lipid bilayer) surrounding them, keeping molecules from moving into and out of the cell. Opioid receptors are integrated into this membrane with parts reaching out of the cell and parts reaching into the cell, allowing it to act like a switch that is turned on from the outside and affects the inside of the cell. 

The human body has different types of opioid receptors called mu, kappa and delta; the mu receptor in particular is responsible for the addictive nature of morphine and other similar opioids involved in the 2010s opioid crisis. A conceptual model of the opioid receptor integrated into the membrane is shown at the top of the page. It shows that the protein is made of a single chain that passes across the membrane multiple times (this structure is shared with a larger group of so-called [[7 pass transmembrane receptors]])

[[Image:Endocytosis.jpg|thumb]]
These opioid receptors interact with opioids via a process known as ligand binding[https://en.wikipedia.org/wiki/Ligand_(biochemistry)#Receptor/ligand_binding_affinity]. When an opioid molecule binds to its receptor, the shape of the receptor changes (a so-called conformational change[https://en.wikipedia.org/wiki/Conformational_change] occurs). This change in the receptor causes it to release a [[GTP-binding protein]] (otherwise known as a G protein), which signals the inside of the cell to behave differently, for example not to cause the sensation of pain. Also, by signalling to other neurons via dopamine binding to the [[dopamine receptor]], large doses of opioids can result in a feeling of pleasure.

The part of the receptor that interacts with the G proteins can also bind to another protein in the cell called [[arrestin]]. Arrestin, as its name suggest, stops a given receptor from always being on. When arrestin is bound, the receptor and a bit of the membrane it is integrated in form a tiny cell-like structure called a vesicle with the opioid binding site pointing inside (see figure at right). Due to increased acidity in the vesicle, the opioid receptor releases the bound opioid.  Then, one of two events may occur; either the receptor is delivered back to the cell membrane, or it is broken down into its building blocks.

To see the physical model of the receptor in action, you can watch a 4:35 min. video [https://www.youtube.com/watch?v=8BcINeVoOWQ (video <span class="fas fa-video" style="color:#338fff"></span>)] that connects the activity of a human individual with the switching of the receptor in the cell.

== Tolerance and Abuse==
[[Image:OpioidWaves.JPG|thumb|Structure of oxycodone with a background of the three waves of the Opioid Crisis: 1) Prescription Pain Medication (in gray) 2) Heroin (in orange) 3) Non-Prescribed (Black Market) Fentanyl (in navy)]]
When opioids are taken on a regular basis, the body adapts and shows less of a reaction. This is called [https://en.wikipedia.org/wiki/Drug_tolerance tolerance]. Once someone is tolerant to opioids, a higher dose is necessary to give the same pain relief. Tolerance also lowers the dopamine-releasing effects brought about by the presence of opioids in the body.  The interaction between opioid receptor and arrestin, discussed in the previous section, is thought to play a role in tolerance. The adaptations in the body also are responsible for [https://en.wikipedia.org/wiki/Drug_withdrawal withdrawal] when not taking opioids for a while, inflicting crippling side-effects and cravings for the next drug dose. Going through multiple cycles of drug intake, withdrawal and craving can lead to a harmful behavior of seeking drugs even though the patient is aware of the dangers of overdose and the toll addiction has on an individual and their community.

This fictional account [https://vimeo.com/377826595 (video <span class="fas fa-video" style="color:#338fff"></span>)] tells a story of how initial exposure through prescribed medication leads to medication abuse and to switching to the even more addictive drug heroin. While some prescription medications include abuse-deterrent features, these have not prevented prescription drug abuse.[https://www.youtube.com/watch?v=n-azUelCgJg (video <span class="fas fa-video" style="color:#338fff"></span>)] .

==Overdose and Treatment==
When untreated, opioid overdose kills people because they stop breathing. The drug naloxone[https://en.wikipedia.org/wiki/Naloxone] can prevent overdose deaths when administered in time [https://youtu.be/_LFWsDXLnkI (video)]<span class="fas fa-video" style="color:#338fff"></span>.

When pregnant mothers take opioids, either self-administered or as part of a opioid maintenance therapy, the fetus will be exposed to the opioids and will become tolerant before birth. At birth, the baby may experience what is called Neonatal Abstinence Syndrome (NAS) [https://www.youtube.com/watch?v=gxQcXtS6lG4 (video)]<span class="fas fa-video" style="color:#338fff"></span>, in which the baby develops withdrawal symptoms after the supply of opioids via the umbilical chord is cut off. The withdrawal after birth inflicts a myriad of health complications. However, if medical support is available and the condition is diagnosed in time, there are multiple treatment options that help the baby to transition to an opioid-free life.

== Structural highlights ==

<StructureSection load='' size='340' side='right' caption='' scene='83/830406/Gpcr/3'>
You can check out the <scene name='83/830406/Gpcr/1'>structure</scene> in the window on the right. It shows the mu opioid receptor <jmol>
  <jmolLink>
    <script>select *:R; selectionHalos ON; delay 0.5;selectionHalos OFF; </script>
    <text>(☼)</text>
  </jmolLink>
</jmol> bound to a peptide ligand <jmol>
  <jmolLink>
    <script>select *:D; selectionHalos ON; delay 0.5;selectionHalos OFF; </script>
    <text>(☼)</text>
  </jmolLink>
</jmol>  and a G protein <jmol>
  <jmolLink>
    <script>select *:A or *:B or *:C; selectionHalos ON; delay 0.5;selectionHalos OFF; </script>
    <text>(☼)</text>
  </jmolLink>
</jmol>. The G protein ("G" because it binds to GTP) consists of three parts A <jmol>
  <jmolLink>
    <script>select *:A; selectionHalos ON; delay 0.5;selectionHalos OFF; </script>
    <text>(☼)</text>
  </jmolLink>
</jmol>, B <jmol>
  <jmolLink>
    <script> select *:B; selectionHalos ON; delay 0.5;selectionHalos OFF; </script>
    <text>(☼)</text>
  </jmolLink>
</jmol>, and C <jmol>
  <jmolLink>
    <script> select *:C; selectionHalos ON; delay 0.5;selectionHalos OFF; </script>
    <text>(☼)</text>
  </jmolLink>
</jmol>). 

Try rotating the molecule after turning off the automatic spinning (+/- spin button). Zooming in on the <scene name='83/830406/Peptide/2'>signalling molecule</scene>, you see it is deeply buried within the protein. Binding results in a change of shape of the receptor (not shown here) to relay the signal to the inside of the cell.

In the 21st century opioid crisis in the USA, the crisis started with prescription opioids like <jmol><jmolLink><script> set refreshing false; load $oxycodone; background image "http://proteopedia.org/wiki/images/6/66/OpioidFatality2.JPG";  select _C; color mediumpurple; hide _H; moveto 1.0 { -977 204 68 164.66} 5.0 -34.67 36.52 {-0.1478 -0.08705 0.2597} 7.521992 {0 0 0} 0 0 0 3.0 0.0 0.0; set refreshing true; moveto 1.0 { -1000 21 -14 66.69} 46.78 -22.06 -16.47 {-0.81575 0.02959999999999985 -0.13314999999999988} 7.056706882620149 {0 0 0} 0 0 0 3.0 0.0 0.0; set zshade on; set zshadepower 1; set spinY 0; set spinX 90; spin on;</script><text>oxycodone</text></jmolLink> </jmol>, then transitioned to use of <jmol><jmolLink><script>set refreshing false; load $heroin; background image "http://proteopedia.org/wiki/images/e/e6/OpioidFatality3.JPG"; select _C; color orange; hide _H; set zshade on; set zshadepower 1; moveto 1.0 { 970 216 -113 30.11} 5.0 -8.1 36.32 {-0.1478 -0.08705 0.2597} 7.521992 {0 0 0} 0 0 0 3.0 0.0 0.0; set refreshing true; moveto 1.0 { 997 68 23 122.37} 42.42 3.87 -19.17 {-0.1478 -0.08705 0.2597} 7.521992 {0 0 0} 0 0 0 3.0 0.0 0.0; set spinY 0; set spinX 90; spin on;</script><text>heroin</text></jmolLink></jmol>, and was made worse when street drugs started to by mixed with <jmol><jmolLink><script>set refreshing false; load $fentanyl; select _C; color black; hide _H; set zshade on; set zshadepower 1; background image "http://proteopedia.org/wiki/images/5/51/OpioidFatality4.JPG"; moveto 1.0 { 802 6 -597 24.36} 5.1 32.85 34.38 {-1.40835 0.0738 -0.28485} 9.158728 {0 0 0} 0 0 0 3.0 0.0 0.0;; set refreshing true; moveto 1.0 { -997 -67 -31 130.64} 55.02 -9.39 -19.75 {-1.40835 0.0738 -0.28485} 9.158728 {0 0 0} 0 0 0 3.0 0.0 0.0; set spinY 0; set spinX 90; spin on;</script><text>fentanyl</text></jmolLink></jmol>.

To explore how naloxone reverses an overdose, let's look at the situation during an overdose. The opioid receptor binding pocket is occupied by <scene name='83/830406/Competition/2'>the opioid agonist</scene>. Every couple of minutes, an agonist molecule will leave the binding site. In the absence of naloxone, another agonist will bind (or the <jmol><jmolLink><script>ago0 = [ {-27.674 -8.743 -15.007},{-27.434 -7.353 -14.448},{-26.336 -8.407 -14.33},{-25.984 -8.850999999999999 -12.878},{-25.934 -10.308 -12.595},{-25.51 -10.46 -11.222},{-25.414 -11.906 -10.78},{-26.812 -12.526 -10.96},{-27.699 -11.843 -10.09},{-26.844 -13.782 -10.383},{-26.608 -13.297 -9},{-27.656 -12.441 -8.864},{-28.181 -11.619 -7.974},{-28.156 -12.113 -6.708},{-29.107 -10.618 -8.263},{-29.238 -10.14 -9.555},{-28.429 -10.775 -10.475},{-28.499 -10.494 -11.86},{-27.259 -10.996 -12.682},{-27.26 -12.476 -12.41},{-26.332 -13.147 -13.263},{-28.656 -13.091 -12.522},{-28.674 -14.519 -12.044},{-28.226 -14.446 -10.537},{-28.194 -15.779 -9.909},{-29.302 -16.538 -9.812},{-30.419 -16.187 -10.19},{-29.118 -17.898 -9.138},{-30.172 -18.853 -9.723},{-30.053 -19.003 -11.252},{-31.056 -19.22 -11.934},{-28.801 -18.878 -11.772},{-28.86 -19.034 -13.196} ]
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ago3 = [ {-36.84158564082973 -32.66185684829452 7.16662312494797},{-35.62570139945715 -33.53068900655996 6.904064193761661},{-36.3677546932709 -32.90591952253823 5.725308917643899},{-37.06556618116485 -33.91216863871839 4.761013400932432},{-38.486778628905945 -33.660358717149606 4.411463773861838},{-38.87369010965448 -34.66920030680424 3.45201228835142},{-40.31375316443563 -34.54477199782743 2.9978845594253425},{-41.194663750126935 -34.66365370269441 4.255289697105706},{-40.99888425987067 -35.960119955197314 4.794737236089999},{-42.5234445669975 -34.76492936348708 3.887086246215187},{-42.364414697329984 -36.05862066779089 3.1766762873025662},{-41.85974643721047 -36.82351601342778 4.1815549155213585},{-41.449205034077224 -38.05869196973595 4.4033771715545615},{-42.22756673376903 -38.99790171640941 3.80383141332889},{-40.67029809559661 -38.45638213342365 5.488800828424376},{-39.926601939454166 -37.52562148447318 6.192725285808963},{-40.084161827962255 -36.22808570661334 5.750365944653884},{-39.48565745320267 -35.12930178778769 6.411087075785401},{-39.4368098601945 -33.81316118140558 5.556291300825402},{-40.88938441092798 -33.56166868292871 5.2543580337425055},{-41.0680967013473 -32.26995769279973 4.672482930964366},{-41.78247355466624 -33.74122539411837 6.483071250405995},{-43.24323762428267 -33.693718537955256 6.119886130205508},{-43.44812536706979 -34.886531053783834 5.113754272575438},{-44.84595885575936 -34.98497156810353 4.656952342808898},{-45.855336044938475 -35.200905352684615 5.521639737559974},{-45.70856988159373 -35.3708711514085 6.731327846355468},{-47.25235216098608 -35.2783262943533 4.905130232933843},{-48.2574644105956 -34.81181110950708 5.971563047504285},{-47.97797792879537 -33.37846895850485 6.463416262042113},{-48.256068667049746 -33.0538523285792 7.619059626092044},{-47.41731353196401 -32.5312296483475 5.557121615996971},{-47.21446506069619 -31.249525656510087 6.16677756406305} ]
anta0 = [ {-26.799271161772232 -12.477052503830866 -10.877820350599679},{-27.35330289625398 -12.33541094249787 -12.286362705408472},{-26.94166361556608 -13.834001058706782 -10.201398116693426},{-27.327900844160254 -10.846984870006597 -12.646334124381745},{-29.067270294546397 -9.84723067451403 -9.371840330883519},{-29.17317221514851 -10.427793308645949 -8.118832289782986},{-25.85274598673054 -8.977733373535035 -13.080417687236116},{-26.826143474001718 -13.01608861604138 -14.119341826476155},{-28.052481583189817 -11.927215777608726 -5.917527731797067},{-28.577311744533382 -11.643018071432433 -7.787887965962726},{-28.644320696735555 -15.405681174835635 -9.946589626825787},{-28.78655312636625 -12.860657456902388 -12.347379809477857},{-28.775395817562256 -14.355982320258217 -12.02305260203125},{-26.530031191127698 -13.063056870842399 -13.199991991553626},{-28.728634333144264 -12.195731331905826 -6.554568888889412},{-28.150685392545313 -14.582294665233416 -10.679139428724662},{-27.81731774868598 -12.269846470837347 -8.781640266073456},{-24.40407768765259 -8.597806465708203 -13.248194693872133},{-27.18313381377088 -13.461621027175042 -8.81134487113218},{-25.362572319065883 -11.961838916265222 -10.826062698469896},{-25.360056029433608 -10.489961628153335 -11.25680303443448},{-28.2239037829546 -9.98129638259427 -11.77628762767387},{-23.97478629918635 -8.14537733220789 -14.400149342696853},{-28.326190970125552 -10.46323152687754 -10.365370302652549},{-25.943142392306157 -10.361912026120638 -12.59702828149235},{-27.67835260275166 -11.62075490336792 -10.000375600449027},{-26.031485633003008 -14.425099007980318 -10.303057078039878},{-27.679736558270406 -10.745438489931537 -13.67294698859603},{-24.978344932962926 -12.047448215599161 -9.80966741924235},{-24.73922964727268 -12.543940442554348 -11.504952834363461},{-29.4006835830534 -12.332859208435444 -11.617720991204237},{-29.190048830912133 -12.706630952417473 -13.348097463129065},{-25.946945122278763 -9.904452996033879 -10.549095747194201},{-24.335473613060323 -10.118404437393696 -11.270670840803527},{-27.829269522036846 -8.965199555889608 -11.770614985377748},{-29.222554629673446 -9.963014564817485 -12.21253375256956},{-29.565070920823608 -8.910483408597496 -9.5745152091391},{-29.798316181765216 -14.732171894470312 -12.014651842957822},{-28.201937387252414 -14.886926237275965 -12.782838667768456},{-29.745184345881363 -9.913088322900567 -7.361096913848015},{-26.322431808213913 -8.309353033406623 -12.358703858889093},{-26.36378285352084 -8.893706937979587 -14.03951540848719},{-23.71986781623744 -8.698502486477828 -12.418674692148713},{-22.93663192514547 -7.873110949032853 -14.520368818043243},{-24.658996170601505 -8.044681311438264 -15.229669344420277} ]
anta1 = [ {-32.056079299153836 -29.43558870241011 -14.991422281330262},{-33.11737520132215 -30.4484419176138 -15.389899924984544},{-31.590990139689218 -29.44087156066089 -13.54132014866609},{-33.59995285103358 -30.084048378276385 -16.797015066146827},{-34.16316036277222 -26.40781626319583 -15.840281626378179},{-33.64041898482418 -25.5727907234508 -14.866746244507272},{-32.91168694893301 -29.95192367381098 -19.11378969059256},{-33.17039097107015 -32.45606387441976 -15.650044147885204},{-31.43735208056781 -24.633290707414172 -13.250023347645401},{-32.68236247623254 -25.984175830191116 -13.94249785240833},{-32.6237415349424 -29.537261741358158 -11.453670662121999},{-34.288691833719945 -30.401899649029456 -14.410275316318849},{-33.7852481775798 -30.80865614253214 -13.023767938016917},{-32.54740607990175 -31.758751442434967 -15.40359371153873},{-32.21448569833907 -25.14260316785571 -12.982126468662583},{-32.6642974413135 -29.906580873785437 -12.60268283215398},{-32.22411429102106 -27.302268014715445 -14.045890037056079},{-31.776958240958034 -30.264699850415408 -20.05490352145797},{-31.373878397790378 -28.021399859277235 -13.282118778105215},{-30.882693439979978 -29.49546743873305 -15.967028565866844},{-31.408305552804695 -29.19393078717572 -17.375848595047135},{-34.285513994129765 -28.730954344268945 -16.88845457735596},{-31.941252442513527 -31.147897155621173 -21.008293612350762},{-33.72438843580922 -27.71630867990647 -15.945563208432748},{-32.46635026868442 -30.14751479780503 -17.72771367412019},{-32.721421016964634 -28.0844304413431 -15.078776743671689},{-30.670750939512633 -30.0128245180548 -13.422219691123725},{-34.32669551859491 -30.83531119863923 -17.10601875526122},{-30.134866962221352 -28.75334937473051 -15.687680506549754},{-30.438548775039898 -30.49075397108837 -15.946284286718942},{-34.691973155155935 -29.390015685066846 -14.37047306442073},{-35.064762718992455 -31.094795902102728 -14.735202282742566},{-31.809893356379238 -28.18097904944369 -17.40350330614343},{-30.591705624819696 -29.2783098958147 -18.092829008754627},{-34.18343108128642 -28.355639429079442 -17.90675656269318},{-35.34568099380119 -28.860952444936977 -16.67144110627551},{-34.91620506448532 -26.036631812561232 -16.51963704942928},{-34.601280520110805 -30.73147361991359 -12.305374373078017},{-33.42884657377233 -31.838213412196335 -13.055714851561733},{-33.992275585262675 -24.552744607890396 -14.822194534574193},{-33.223990772348856 -28.916825941859784 -19.25252291368404},{-33.75060994650427 -30.61565368321464 -19.322974390709646},{-30.828344109333695 -29.760647188636373 -19.94333106322537},{-31.128070424302305 -31.372028614754477 -21.682716554045882},{-32.88986657413786 -31.65194981740018 -21.119866070583356} ]
anta2 = [ {-30.12867999271322 -25.125521311683777 -21.264783214811697},{-31.262479435589253 -26.138138563521462 -21.254286328862843},{-29.79483641779191 -24.43289397764071 -19.95026890388915},{-31.575397363983445 -26.49787553696342 -22.709727341074718},{-31.786051712274855 -22.80958735474765 -23.758240178608617},{-31.255694056172214 -21.63203775174155 -23.257845305459924},{-30.678220162476055 -27.58101231651991 -24.67962564704571},{-31.52692888711852 -28.00028445440592 -20.503612778877294},{-29.10642414872407 -20.14089707556481 -22.030207191523598},{-30.435994304642325 -21.5818302926794 -22.132271408109595},{-31.00880171231719 -23.413229156680593 -18.241257842899632},{-32.500804420627844 -25.54029788537112 -20.588740714364437},{-32.17040548054702 -25.228687593737643 -19.127561520513925},{-30.850465633353277 -27.310785072961753 -20.549227352135002},{-29.95801185379403 -20.401997847518214 -21.65373760781328},{-30.992486998493465 -24.304007983416753 -19.056437137258495},{-30.127648092814507 -22.799492957827994 -21.515612184912012},{-29.51053499386597 -28.387604358616912 -25.186630622005367},{-29.436666562753235 -23.089157771775195 -20.392207965285305},{-28.890214121419962 -25.733002968224838 -21.920066193842896},{-29.25290438475294 -26.14541287048088 -23.351967086155156},{-32.08766330140391 -25.33402107977635 -23.541740046413146},{-29.693631956923706 -29.61762976669589 -25.59832921029444},{-31.495689326979598 -24.018760510253983 -23.150500608390864},{-30.380602922772017 -27.08370753624756 -23.329848145325812},{-30.621521778456287 -23.96247857967453 -22.08963327860878},{-28.961527649155602 -24.921432892016902 -19.445212951291797},{-32.35539607712643 -27.259201946869855 -22.70547116035972},{-28.08785394171711 -24.995622958046887 -21.942602001286442},{-28.56886798784718 -26.608819667218107 -21.35617625582101},{-32.78503044573256 -24.622275390986463 -21.10311360095253},{-33.321407786135694 -26.25625212501883 -20.633332341914883},{-29.529483618522622 -25.260260311483698 -23.92478262779845},{-28.392706992074192 -26.624086501685248 -23.819886086002633},{-31.854562352566674 -25.524200539223145 -24.589459885327972},{-33.170549568063876 -25.276172077354932 -23.43238170700497},{-32.42884188405809 -22.784174722590496 -24.625738307243928},{-33.03100455950107 -24.755561605337967 -18.654828758369916},{-31.93530607239886 -26.155328916335197 -18.60402068395673},{-31.48850043127928 -20.707586476823476 -23.765263310670427},{-30.854250604812837 -26.737406501558407 -25.347121274247762},{-31.5676311560505 -28.210279549513615 -24.64709267931537},{-28.522794129995074 -27.951507383436095 -25.210582325028028},{-28.85683145429383 -30.195642651035538 -25.961664089346467},{-30.681372820794603 -30.053726741876677 -25.574377507271787} ]
anta3 = [ {-44.40452541742169 -26.79094830268958 -38.09782553518803},{-44.13267699714565 -28.285840137607515 -38.14683470054618},{-45.43821383520574 -26.298698106709907 -37.093679116832064},{-43.27071051632155 -28.55935964328051 -39.38289203172147},{-45.61853168957865 -26.56515523053607 -41.67594864650364},{-46.52790361339627 -25.540868917041987 -41.47057680773078},{-41.08843474823195 -28.170048957151856 -40.35485973266369},{-43.21652580436286 -29.626153645109326 -36.93635615733664},{-47.341780004276835 -23.100450794068045 -40.154551885691795},{-46.77498319167446 -24.979002051360894 -40.21973613952096},{-47.57851812177168 -26.951371155071776 -36.44002604153191},{-45.4457199423656 -29.060248395412422 -38.24695105411422},{-46.266777550754696 -28.799607774021425 -36.982340465756145},{-43.42343489887834 -28.682194430543817 -36.97131681871012},{-47.697641773315645 -23.993879534870093 -40.053299397102954},{-46.494091019740196 -27.327154828735893 -36.81562537724363},{-46.03222579089396 -25.474544039427276 -39.14233281130581},{-39.72732033213607 -27.589037977354764 -40.07038265511415},{-46.07725633883485 -25.206122804219884 -37.819714003696504},{-43.08926797165946 -26.023036303698536 -37.98541346656264},{-42.22066871725118 -26.369619306595915 -39.200889454537744},{-43.953069465903845 -28.234533665293334 -40.701259612462756},{-38.67369303659788 -28.367198633137242 -40.05254320755545},{-44.88544007373822 -27.069713318675987 -40.61587542333599},{-42.00800955276085 -27.819915884646505 -39.26418270420223},{-45.08151243814945 -26.451459757009154 -39.40257652718533},{-44.96431444774695 -25.944991747700463 -36.178000968046966},{-43.03345537610803 -29.623112534754085 -39.39607513924217},{-43.289781981047916 -24.95177146477221 -37.97110343794395},{-42.572294391295614 -26.31252152990077 -37.07041253158148},{-46.0032541507943 -28.723092762339064 -39.120799373628984},{-45.23573759289405 -30.12628328992048 -38.33324002560828},{-42.72103868171063 -26.036957055714172 -40.11032581597547},{-41.25800602483882 -25.865966007804868 -39.11353909532688},{-43.18788959490801 -28.015637518229532 -41.4461122031298},{-44.51543070304103 -29.10896881547759 -41.02846203771027},{-45.48115173622975 -26.971901514132867 -42.66693917077626},{-47.227829189817236 -29.3072598526196 -37.06373060121632},{-45.72837731840831 -29.183168784280895 -36.11571654431266},{-47.07170140857883 -25.15865392303784 -42.32173933998471},{-41.46721822462468 -27.765534807746228 -41.29352862047373},{-41.0117064004967 -29.254645940067107 -40.431343098861525},{-39.620575239633865 -26.531101012599763 -39.8812765107623},{-37.69828811680373 -27.950818492586414 -39.84868288528512},{-38.780438129100126 -29.425135597892243 -40.24164935190731} ]
ROTATE COMPARE {bf0} @{ago1} 100; 
ROTATE COMPARE {bf0} @{ago2} -1; 
ROTATE COMPARE {bf0} @{ago3} -2; 
ROTATE COMPARE {bf0} @{ago2} -1; 
ROTATE COMPARE {bf0} @{ago1} -1; 
ROTATE COMPARE {bf0} @{ago0} 100; 
</script><text>same molecule will rebind</text></jmolLink></jmol>), maintaining the "on" state of the receptor. In the presence of naloxone, however, <jmol><jmolLink><script>ROTATE COMPARE {bf0} @{ago1} 100; 
ROTATE COMPARE {bf0} @{ago2} -1; 
ROTATE COMPARE {bf0} @{ago3} -2; 
ROTATE COMPARE {2.1} @{anta2} -2; 
ROTATE COMPARE {2.1} @{anta1} -1; 
ROTATE COMPARE {2.1} @{anta0} -1;</script><text>naloxone replaces the agonist</text></jmolLink></jmol>. Because naloxone is an antagonist, the receptor is now in the "off" state, saving the patient and causing instant withdrawal symptoms. The opioid that caused the overdose is still there, but it is <jmol><jmolLink><script> 
ROTATE COMPARE {bf0} @{ago2} -1; 
ROTATE COMPARE {bf0} @{ago1} -1; 
ROTATE COMPARE {bf0} @{ago2} -1; 
ROTATE COMPARE {bf0} @{ago3} -2</script><text>blocked from binding to the receptor</text></jmolLink></jmol>.

Select how you want to show the protein:
<jmol>
  <jmolRadioGroup>
    <item>
      <script>select protein and not 1000-1161; isosurface id "isosurface1" select {selected} ignore {not selected} saSurface 1.2;
  isosurface ID "isosurface1" fill noMesh noDots notFrontOnly frontlit;
  color isosurface opaque [xffa500];</script>
      <text>surface</text>
    </item>
    <item>
      <script>select protein and not 1000-1161; spacefill only; isosurface off</script>
      <text>all atoms</text>
    </item>
    <item>
      <script>select protein and not 1000-1161; cartoon only; color group; isosurface off</script>
      <text>rainbow</text>
      <checked>true</checked>
    </item>
   </jmolRadioGroup>
</jmol>


</StructureSection>

== Further reading ==

* [https://ny.pbslearningmedia.org/resource/nva-sci-collectionguide/ NOVA: Addiction]: A teaching guide answering frequently asked questions about opioid abuse and treatment.
* [https://www.nejm.org/doi/full/10.1056/nejmra1507771 Review article] on prescription opioid use and abuse by Nora Volkow and Thomas McLellan
* [https://www.ncbi.nlm.nih.gov/books/NBK22592/ Membrane receptor and G-proteins]: Chapter in the Berg/Tymoczko/Stryer Biochemistry textbook on membrane receptors and events mediated by G-proteins inside the cell.
* [https://www.oercommons.org/courseware/lesson/60267 Lesson plan] for a discussion based on five student-made videos