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resorcinol
01-27-2009, 05:36 PM
that you may encounter if you're looking up literature on opioids exists.

One that I recently discovered was a different, shorter way to describe the three important subtypes.

OP1 receptor = delta opioid receptor
OP2 receptor = kappa opioid receptor
OP3 receptor = mu opioid receptor

I mention this only because I've come across several pieces of medical / pharmacological literature on opioids that never once mention mu, delta or kappa. They ONLY mention OP1, OP2, and OP3 receptors.

The synonyms for these receptors that refer to the same receptor can cause confusion. Hence the clarification above: what each OPx receptor corresponds to the names we're more familiar with, the mu delta kappa naming convention, since I'm seeing the abandonment of that nomenclature in quite a bit of academic articles.

Most important thing to remember is that mu opioid receptor is the OP3 receptor, since that's the one we're most interested in since it's primarily responsible for the anti-nociception / analgesia opioids produce and almost entirely responsible for the euphoric recreational effects.

I kinda actually like the new nomenclature better. Typing out mu opioid receptor repeatedly in a post gets tedious, and just typing mu receptor is vague and not a good practice because for people not well versed in opioids and their pharmacology, they have no way of knowing that a "mu receptor" is an opioid receptor. Sure, on opiophile, the context makes it clear. Otherwise though, being clear directly is a good thing.

Adoption of this new nomenclature allows for clarity without the tedium of typing mu opioid receptor out.... a long receptor name compared to most other receptors.

OP3 receptor is short, and provides clarity that one is talking about the opioid receptors (or at least it will if that nomenclature begins to take over). Its better because shorter names are just easier to use. CB1 receptor is the cannabinoid receptor responsible for the psychactive effects of MJ, which acts as a partial agonist of that receptor. It's a short name, and the CB indicates that cannabinoid receptors are the receptors being referred to. OP3 receptor is a nomenclature more similar to that used for the cannabinoid receptors, in that "OP" cues up "ok, we're talking about opioid receptors" in the reader (this will become more true as the nomenclature is switched over to this version). OP3 receptor agonism is responsible for the desired effects of opioids just like CB1 receptor agonism is responsible for the desired effects of MJ.

It also makes sense to use similar receptor nomenclature for cannabinoid and opioid receptors since they're both neuromodulatory transmitter systems and function in remarkably similar ways, just in different areas of the brain.

CB1 receptors are PRE synaptic and their agonism inhibits the release of GABA from the axon terminal resulting in less stimulation of post-synaptic GABA(B) receptors and increased action potential firing in these post synaptic neurons. OP3 agonists (what we more commonly call mu opioid agonists using the old naming system) do the exact same thing. The effects of MJ and opioids are so different because CB1 receptors are expressed in different areas of the brain than OP3 receptors, with some overlap.

The CB1 receptors are located in brain regions that increased synaptic activity of post-synaptic neurons results in the thought changes and perceptual changes of the MJ high. CB1 receptors are not present prolifically in the VTA region, so their effect on dopaminergic neuron firing is minimal.

OP3 receptors are highly expressed in the VTA, and thus their disinhibition of post synaptic neurons when bound by an agonist (since these post synaptic neurons in the VTA are dopaminergic and project into the nucleus accumbens... this is the mesolimbic pathway portion of the limbic system) tends to cause intense euphoria because of the neurons they disinhibit (dopamine inter-neurons in the "pleasure pathway" of the brain!).

So in a lot of ways, having opioid receptor nomenclature match cannabinoid receptor nomenclature makes a lot of sense.

The most important thing to remember is that OP3 receptor is the mu opioid receptor, so OP3 receptors are likely the ones you're interested the most in when looking at opioid scholarly literature.

Narkotikon
01-27-2009, 05:39 PM
That's interesting. I've never heard of the OP1, 2, 3 thing before. Usually it's either delta, kappa, or mu, or the Greek letters for d, k, m.

blutuesday
01-27-2009, 06:49 PM
omg..thank you SO much for posting this,.


you have no IDEA how much u helped me.

Do u mind if I copy and paste this into word pad for my own personal reference on my laptop?

Mayo
01-29-2009, 12:34 PM
Do you know what group of people (scientists) introduced this CB or OP convention
resorcinol? Was it biochemists, molecular biologists, cell biologists, neurobiologists, pharmacologists, etc?

I remember when I was young and seeing the delta-9 THC thing.
We all thought we were so smart, 'the delta means it needs heat to be activated'. :rolleyes:

I never went to high school, so even through college gen chem the delta meant heat,
or a change in temp (delta-H). (This was before there was much of anything on the internet.)
It wasn't until I opened my biochem textbook that I realized the delta was the biochemist's convention
for stating the location of double bonds in a hydrocarbon chain..

So I was just wondering who began using the convention you are talking about.
Who names receptors?

resorcinol
02-01-2009, 08:50 PM
omg..thank you SO much for posting this,.


you have no IDEA how much u helped me.

Do u mind if I copy and paste this into word pad for my own personal reference on my laptop?

No problem, you can copy it to word pad :)


Do you know what group of people (scientists) introduced this CB or OP convention
resorcinol? Was it biochemists, molecular biologists, cell biologists, neurobiologists, pharmacologists, etc?

I remember when I was young and seeing the delta-9 THC thing.
We all thought we were so smart, 'the delta means it needs heat to be activated'. :rolleyes:

I never went to high school, so even through college gen chem the delta meant heat,
or a change in temp (delta-H). (This was before there was much of anything on the internet.)
It wasn't until I opened my biochem textbook that I realized the delta was the biochemist's convention
for stating the location of double bonds in a hydrocarbon chain..

So I was just wondering who began using the convention you are talking about.
Who names receptors?

I'm not sure who started this convention Mayo. I just know it's out there because I've seen it while scouring articles about opioids. I've seen it used exclusively over mu, delta, kapps.

I'll look into it b/c I'd like to know too. If you want to know now, you can look into it too of course.


I do want to say one thing though.

I really, sincerely hope that nobody here thinks I'm trying to be an intellectual snob or faux-intellectual or whatever. I've NEVER claimed to be infallible, nor have I EVER claimed that there are no mistakes in my posts of a technical nature. In fact I'm sure there ARE mistakes. I'm NOT perfect and I know that.

I only write stuff that is technical in nature to try to enrich the board. I mean, without that kind of stuff, the board will get stale....

It'll be "How do I break down avinza for IV" or "Is oxycontin more bioavailable orally or nasally or rectally" or "how bad are done w/ds really / do they really last a month or longer?" or "Morphine sucks orally" or "Oxycontin vs morphine IV and oral" or "bupe doesn' seem to have a blocking effect for ME" or "bupe does/doesn't stop cravings for ME" or "does the naloxone in suboxone have any effect" etc etc etc.... threads that tend to recur even though they've already been thoroughly hashed out.

Yes, sometimes the stuff I try to post about pushes me right to the limits and sometimes past my formal education status currently, but I'm not a total theorist either (not that there's anything wrong with that).

In the other thread you mentioned knowing about blots and immunoassays and PCR ---- that's awesome and I'm very glad that you have found enough motivation in your life to enter a productive career. BUT that doesn't mean I'm totally clueless about the actual procedures and only understand in theory (again, not that there's anything wrong with that ... only knowing in theory is better than not knowing at all).

I've done ELISA, western blotting, and a PCR with taq polymerase in a biochemistry lab. I've done separation based on polarity (A/B), synthesis of aspirin, and a few others in orgo chem lab (I ADMITTEDLY only took orgo chem I lab ... I took orgo chem II also but not the lab since my addiction made it necessary for me to move back home for awhile and take classes at a university more locally). So yeah, I'm NOT anywhere near as experienced as you or robojunkie. I'm acutely aware of that. That's why I often refer people to you guys when I'm not sure (well, robojunkie mostly honestly, i wasn't aware you were a chemist until very recently).

But I'm no pretender either.

Sure sometimes I try to post about stuff that really pushes the limits of concepts that I've grasped into the realm of what I haven't quite grasped yet, but that often helps me learn.

I don't just use science and interest / aptitude in it as a "status symbol". Status is meaningless to me. It is in fact one of the reasons I can get so apathetic about school and American society in general.

I have a genuine interest. I wouldn't have spent $500 on labware in 10th grade in high school if it was superficial. I wouldn't have spent countless hours doing experiments with my best friend if it was superficial. Nor would I have petitioned the school to allow me and a chemistry professor I'm friends with to start a chemistry club, where we'd bimonthly do different experiments in inorganic chem to help interested students learn more that the rote textbook learning allows. I was president of the chemistry club for all of senior year, a junior took over for me when I graduated from high school. AFAIK the club is still going , and is more successful than ever this year. The year I got it started w/ one of the professors we only got about 6 members. I've heard through the grapevine that membership this year (2008-2009) is 25 kids. I was a HS senior in 2006-2007.

None of this is directed at you in particular Mayo, I just wanted to clarify that because I realize it could definitely come off that way.

I just know there's an air of mistrust... almost a miasma of poisoned air that has hit opiophile with a vengeance after the oxycontinously and dboyjake "scandals".

... and I want to promise you guys that I'm not some pretender. The persona I am on opiophile is the real me. There's no facade. I only conceal details about certain things to protect my ability to use this site without worrying about loosing a valuable resource for support from other people with this forbidden love of a very special class of chemicals.

Edit: Also, I'm really not sure it particularly matters who names receptors. If I had to guess I'd say the discoverers do, but sometimes if a naming system deemed more suitable or concise begins to make its way into widespread usage... it could take over. I could see this happening with "delta opioid receptor" "kappa opioid receptor" and "mu opioid receptor" becoming OP1 receptor, OP2 receptor, and OP3 receptor respectively. It's a possibility for a number of reasons. Opioid really need not be spelled out, since it's jargon to the average person anyway. Also, the names are so long. Yes, "delta" for example is really a greek symbol that's one character, but with a standard keyboard that'll take you longer to type than just typing delta will. That's just a few superficial reasons. The more scientific reason is to more closely resemble the endocannabinoid neurotransmitter system receptor naming scheme, since that neurotransmitter system functions very similarly to the opioidergic neurotransmitter system. I believe the differences in effect of agonists on the receptor that produces the most desired psychoactivity in each system has much to do with receptor distribution in the brain (CB1 is the receptor that is recreationally targeted with agonists in the endocannabinoid system, OP3 / mu opioid is the receptor that is recreationally targeted most often with agonists in the endogenous opioid system --- both work by inhibiting GABA release onto post synaptic dendrites that contain inhibitory GABA(B) receptors, so the quite different psychoactive effects seem to be due to the fact that CB1 is dense and sparse in different brain areas than where OP3 is dense and sparse, with some minor overlap of course). If I'm incorrect about OP3 and CB1 receptors having very similar if not identical effect of preventing GABA release into certain synapses in which the post synaptic neurons contain primarily inhibitory GABA(B) receptors (which are GPCRs unlike the ionotropic A subtype), please correct me. I'm certain that this is what opioids do, but not sure about cannabinoids.

OP3 agonism slows nociception for the same reason it inhibits GABA release from the terminal button just near where the OP3 receptors are located on the terminal button at the end of axons. The difference is that on the nerves that carry pain signals the neurotransmitter released that is modulated by OP3 is excitatory, so when OP3 agonists attenuate action potential propagation along a neuron carrying a pain signal, the release of the exititory neurotransmitter is decreased, thus the receiving dendrites are depolarized and action potential initiation is more likely to fail. This attenuates the pain signals. This is the exact opposite of what happens in the VTA where OP3 agonism's action potential propagation attenuation on the sending neuron projecting into the VTA decreased the release of the inhibitory neurotransmitter GABA from the terminal button which stimulates inhibitory GABA(B) GPCRs that hyperpolarize the dopaminergic neuron that projects from the VTA to the NAc. When mu agonism on the sending neuron causes attenuation of the action potential and significantly less GABA release, the GABA(B) receptors on the receiving dopaminergic neuron are stimulated less, thus the neuron is not as hyperpolarized, and action potentials successfully fire more frequently --- and when these action potentials reach the terminal buttons in the NAc containing dopamine, dopamine is released. More mu binding in VTA --> less hyperpolarizaiton by GABA binding to GABA(B) receptor at the dendrites of the dopaminergic neurons carrying signals from VTA to NAc --> dopaminergic neuron less hyperpolarized, action potentials fire more frequently than normal --> this much higher than normal frequency of action potentials reaches the terminal buttons of the dopamine neuron in the NAc and much more dopamine is released than normally due to more action potentials coming down the pike --> euphoria. In this way opioids are not properly categorized as "downers" IMO, since they inhibit areas of CNS where they decrease the release of exitatory neurotransmitters (like on neuronal pathways that carry nociceptive signals (pain)), but excite other areas where they inhibit the release of inhibitory neurotransmitters (like the mesolimbic "reward" pathway, VTA --> NAc). They're "neuromodulators".

The opioidergic neurotransmitter system is a neuromodulator system. Other neuromodulator neurotransmitter systems are the cannabinoid system (target of mary jane and synthetic CB1 agonists) and the adenosine system (target of coffee and pure caffeine isolate, and related purine derivative compounds like theophylline; they're antagonists of multiple adenosine receptor subtypes)

Mayo
02-02-2009, 03:01 AM
hmmm..I'm not sure why you mentioned some of that resorcinol, but I hope it wasn't because of what I said.
I was just strolling down memory lane for a brief moment. honestly. It seems like you got defensive there,
but I wasn't trying to question your understanding or anything like that.

Sometimes I wonder why you go into as much detail as you do, when it doesn't always seem relevant or necessary,
but I usually find these topics interesting, tho not really why I spend time here at the 'phile.
And maybe you think it is all relevant, which is great. I have no issue with that, or you. More power to you IMO.
But I go to other websites for serious discussions about science, which I have to anyway for my work (its expected of me).

I did look a little into receptor naming conventions/authority, but just online, and didn't find out much.
I do know figuring these things out is almost always a combined effort involving a few different disciplines.
I'll find out soon and let you know if you don't post it first. Maybe there isn't such an authority for this, like IUPAC.
I'll ask the director of research here, he probably knows. And if he looks at me like I'm stupid, that's OK,
he does that pretty much every time I speak to him...egomaniac that he is - MD and PhD, ooooooh :rolleyes:
he's very smart, but you don't have to be a dick about it, right?

Where did you do the molecular biology techniques you mentioned?
I didn't do them until grad school, well, besides some basic DNA isolation and PCR in microbiology.
But then I was heavy into chem as an undergrad, didn't get serious about biochem and mol bio till later.
The school I went to was 'old school' in that sense, only offered undergrad degrees in chemistry and biology.
Which is great for learning the basics, but bad for getting a job outside of chemistry.



Also, I'm really not sure it particularly matters who names receptors

It matters to me, a little. I like to know who is responsible for what in the field of biochemistry.
And I think it is a biochem or mol bio issue, tho those in highly specialized fields like neurobiology may object.
After all, there are receptors outside the brain, right? :p

resorcinol
02-02-2009, 06:49 AM
No, it wasn't on the defensive b/c of your post per say, but for some reason it made me think about what people think about the stuff I post here. I'm a bit self conscious still to this day by nature; I've been burned a few too many times by people I thought were friends (and once by a more than friend which I talked about in the HIV thread). I wanted to assert that I'm no faker I suppose because I detect a general suspicious environment surrounding the site recently (understandably, after several recent incidents).

I understand why you care who names receptors. I'm just genuinely not sure when this OPx naming system appeared first. I've just been seeing it in academic papers increasingly often. It might be time to do some digging to find out.

I do hope I get a chance to gain more lab experience, which I will if I decide on moving down the path towards being a psychiatrist, which requires a full MD doctorate degree (ie lots of organic chem and biochem courses and their lab requirements).

Admittedly most of my understanding is purely theoretical at this time. Much of the organic reactions I understand in theory I've never actually DONE or even seen for that matter. To that effect, robojunkie and you are far more qualified in the field. I also wanted to make it clear that I'm aware of that fact completely (I lack lab experience). There are also some orgo reactions that are very complex and beyond my understanding... something I hope to remedy through more schooling.

I mean, I know the stuff orgo I and II teach you. Nucleophilic substitution (SN1, SN2), addition reactions (electrophilic, nucleophilic, FR), aromatic nucleophilic substitution, electrophilic substitution, etc. Also a few specialty reagents that are widely useful like grignard compounds (R-MgBr) that attack eletrophilic carbons. Of course redox too. But theory and practice are different. It's not so tough to understand some orgo reactions in theory but many (most might even be fair to say... since chemical equilibrium complicates so many reactions, and often more than one thing is going on simultaneously) of them are very tempermental and requre skill that I know I don't have yet.

EDIT: I knew it would seem as if my post (the one above) was a defense of myself against your post, but that wasn't my intention which is why I said

"None of this is directed at you in particular Mayo, I just wanted to clarify that because I realize it could definitely come off that way."

in the above post. It just triggered me to question myself (lord knows it doesn't take much) and my own motivations with regard to this board. If that makes sense (it probably might not make sense but I can't explain my trigger for thinking about something very well sometimes).

I mean Shelley made a valid point in a post on my profile that I might be annoying to some opiophiles (she was referring to my gay related threads, but I realized it could also apply to my extensive, somewhat off topic threads of a very technical nature). I responded to her in a way "she didn't expect" (her words) because she has / had a valid point. Shelley and I have reached a mutual respect for each other now despite our differences of opinion (yes shelley, the sentiment of MAD RESPECT is mutual).

The reason for OT posts from me outnumbering opioid related posts nowadays is simple: I'm on a very super slow taper that is so slow that it's almost maintenance. There isn't much to say about that without becoming repetitive. Yet, I don't want to leave opiophile, so I post about what I can that is at least somewhat "fresh". Yeah I break the rules and catch a buzz once in a blue moon, but there ain't much to say about that either.

I know my readership is probably restricted to a few posters in threads like this (I'm not counting the ones who graze the post then move on to the next in "new threads" ... counting those, readership is definitly larger obviously), but I'm OK with that.

I would stop doing this-or-that if an admin or mod had a problem with something, but otherwise I see it as OK. I've always been one of the members here that has stood behind OT posting as being OK, and part of that is because I post OT sometimes --- a lot more now that I'm on "boring maintenance with slow taper" status.

Also, even among the using actively to get high daily crowd which I belonged to not that long ago, things can get stale. I mean how many threads do we really need about shooting up Avinza? I don't have a PROBLEM with questions being repeated -- to be clear on that point, but it DOES get boring, that's nearly undeniable.

I think anything more I might say would be classed "rambling" by my own standards too, so that's about it.

Edit again: I said "The difference is that on the nerves that carry pain signals the neurotransmitter released that is modulated by OP3 is excitatory, so when OP3 agonists attenuate action potential propagation along a neuron carrying a pain signal, the release of the exititory neurotransmitter is decreased, thus the receiving dendrites are depolarized and action potential initiation is more likely to fail." in my post above. Perfect example of a mistake due to typing faster than thinking (bolded part is the error / incorrect part). I meant ".... the receiving dendrites are not as depolarized and action potential initiation is more likely to fail". (correction is bolded).

Now I won't ramble anymore, but I HAD to fix that or it would annoy the HELL out of me seeing it there.

Mayo
02-15-2009, 03:53 PM
I have not received a difinitive answer as to who is responsible for naming receptors, because apparently there is no one answer.
Even how receptors should be named is still a matter of contention, and depends largely on what type of scientist is asked.

A biochemist may say since receptors are proteins, they should be named by listing the amino acid sequence or
advocate for IUPAC to be the responsible entity (not likely).

A pharmacologist may say it should be based on the type of ligand (drug), agonist/antagonist result etc,
and in this case the international union of pharmacology, committee on receptor nomenclature seems to be the responsible entity.

Medical researchers may say the receptor should be named based on its biological function, like protein allergen receptor,
and is most like the position of pharmacologists, tho may say the AMA should be the leading authority (HA!).

Molecular biologists may say that allele type and locus should be considered in naming criteria,
and would like to see the genetics society of america in charge (just kidding).

Anyway, all I have determined is that there apparently is no overall authority.
There should be one, but given the many kinds of receptors and the many types of scientists involved in this research,
I guess it will take even more time to work this out.

Ickyuck
02-15-2009, 03:59 PM
Holy crap I came across this subject like a month ago and was totally miffed by these seemingly re-named receptors. Thank You Resorcinol Very Much So. :)