Actual Number of Opiate Receptors

[daddysgone]

Does anyone have any info on the approximate number of opiate receptors the average person has in their brain? Specifically the number of mu receptors. Obviously no one can give an exact number- but on what order of magnitude. Do they number in the hundred? thousands? more?? any ideas?

ps-neglecting the effects of any down-regulation.

 

[wungchow]

Well, let's say you took 100mg of oxycodone = 0.1 grams.

The MW of oxycodone is 315.364 g/mol

.1 g oxy = .000317 moles

.000317 moles * (6.02 x 10^23 molecules/mole) = 1.908 *10^20 molecules

I would say the number of receptors is at least 10^20.

 

[MurphyClox]

???

And why are 100 mg oxycontin thought be be equivalent to the number of µ-receptors? Is there any special reason?

 

[wungchow]

I'm just getting a general idea for the order of magnitude. Safe to say the # of molecules in 100mg of oxycodone is occupying enough receptors in an opiate-naive individual to be within a couple orders of magnitude of the total # of receptors.

 

[MurphyClox]

OK, that makes sense to me. But I fear, the number could still be significantly higher (several magnitudes). Personally, I have no idea whatsoever...

 

[Hammilton]

I have seen some older researcher that showed receptor proliferation was at least part of what causes tolerance.

 

[daddysgone]

So any other opinions on this matter?
Wungchow- that is an interesting and clever method you employed, and my guess is that your answer probably got us in the right ballpark, but i also guess that we are dealing with a HUGE ballpark. I think that your math likely proved the MINIMUM number of receptors to be found, but i dont see why its not possible that we might have way way way more then that. My thinking is that perhaps we only need a tiny fraction of our receptors activated to produce an effect. So, those 100 mg of oxy might all reach a receptor, but perhaps that still leaves 99% of our receptors unoccupied. then again- it could be just the opposite- that a signifigant percentage of our receptors need to be activated to produce an effect.
If the latter is true, then your math probably gets us pretty close to an answer. If the former is true, then theres no telling how many receptors we are dealing with.

Surely, there must be an answer out there regarding this. I can't imagine the medical field has not explored this and found an answer.

 

[nuke]

An adult brain has roughly 100 billion neurons... mu-opioid receptors are fairly common and present throughout the body, not just in the brain.

Here's a study on receptor density in primates and brain regions:

The aim of this study was to investigate the relative density of µ-, -, and -opioid receptors (MOR, KOR, and DOR) and guanosine 5'-O-(3-[35S]thio)triphosphate ([35S]GTPS) binding stimulated by full agonists in cortical and thalamic membranes of monkeys. The binding parameters [Bmax (femtomoles per milligram)/Kd (nanomolar)] were as follows: [3H][D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO) (MOR; 80/0.7), [3H]U69593 [(5,7,8)-(–)-N-methyl-N-(7-(1-pyrrolidinyl)-1-oxaspiro(4,5)dec-8-yl) benzeneacetamide] (KOR; 116/1.3), and [3H][D-Pen2,D-Pen5]-enkephalin (DPDPE) (DOR; 87/1.3) in the cortex; [3H]DAMGO (147/0.9), [3H]U69593 (75/2.5), and [3H]DPDPE (22/2.0) in the thalamus. The relative proportions of MOR, KOR, and DOR in the cortex were 28, 41, and 31% and in the thalamus were 60, 31, and 9%. Full selective opioid agonists, DAMGO (EC50 = 532–565 nM) and U69593 (EC50 = 80–109 nM) stimulated [35S]GTPS binding in membranes of cortex and thalamus, whereas SNC80 [(+)-4-[(R)--((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethyl-benzamide] (DOR; EC50 = 68 nM) was only active in cortical membranes. The magnitudes of [35S]GTPS binding stimulated by these agonists were similar in the cortex, ranging from 17 to 25% over basal binding. In the thalamus, DAMGO and U69593 increased [35S]GTPS binding by 44 and 23% over basal, respectively. Opioid agonist-stimulated [35S]GTPS binding was blocked selectively by antagonists for MOR, KOR, and DOR. The amount of G protein activated by agonists was highly proportional to the relative receptor densities in both regions. These results distinguish the ability of opioid agonists to activate G proteins and provide a functional correlate of ligand-binding experiments in the monkey brain. In particular, the relative densities of opioid receptor binding sites in the two brain areas reflect their functional roles in the pharmacological actions of opioids in the central nervous system of primates.

http://jpet.aspetjournals.org/cgi/content/abstract/306/1/179

My guess is it's in the hundreds of millions, discounting receptors elsewhere in the body.

edit: billion not million, hah

 

[mad_scientist]

Google says that there are more like 100 billion neurons in the brain, possibly up to as many as a trillion. Now obviously not all of those will express mu-opioid receptors, but the ones that do will have hundreds of individual receptor complexes per cell I would imagine.

Obviously not all of those will be occupied at one time, remember that drugs don't simply bind to a receptor and then stay bound for the entire duration of the drug effects, instead drug molecules will be binding and unbinding to each receptor hundreds of times a second, with higher affinity drugs binding more often and for longer each time (hence the receptor spends a higher proportion of its time in the occupied and active state)

Also you are correct in saying that you don't need anything near 100% receptor occupancy in order to get a 100% response inside the cell, due to the large number of individual receptors per neuron. And remember that at any one time a large proportion of the opioid molecules will be bound to other non functional targets like plasma proteins, or just floating around in the bloodstream and tissues, so the proportion of opioid molecules that are in the immediate vicinity of the active site of a mu-opioid receptor (and hence available for binding) will always be fairly low compared to the total number of molecules in the body.

I would estimate the total number of receptors to be in the low trillions.

 

[nuke]

^^ Right you are, haha, we'd be some pretty dumb humans in that case.