Tuesday, May 22, 2012

Similarities between neurotransmitter receptors

I did some BLAST comparison in NCBI to check which neurotransmitter receptors were similar and possibly related from some common ancestor gene. Gene duplication can create several copies of gene that can evolve in different directions.
I compared human receptors with fruit flies (drosophila melanogaster) receptors and there didn't seem many differences between searching human proteins or fruit fly proteins. Seems like these receptors formed some time before humans and flies separated in evolution.
In general if  receptor was ion channel then it was similar to other ion channel type proteins and rest of receptors use G proteins that inhibit or enhance metabolism with way more complex mechanisms than ion channels that let certain types of ions in one direction (towards environment with smaller ion density).

Yellow names on images were proteins that other proteins got compared with.

Longer distance between points in these evolutionary trees show larger differences. Triangular parts have many closely similar results that don't show up in main tree view.

BLAST search results were at least 25% identical to protein that was searched. I always left out most result for being too similar or too unknown and also because trees become unreadable due to different overlapping names in the same place.

Results had somewhat predictable similarities. For example dopamine and serotonin receptors can both create euphoria and both had similarities with opiate receptors. Proteins that transported neurotransmitters back to neurons after nerve impulse seemed mostly related with each other.
Many substances that are released during wakefulness have also related receptors. For example one "family" of interrelated serotonin (5-HT1, 5-HT7), dopamine, histamine, acetylcholine (M3) and adrenaline receptors.


Protein family that involves free fatty acid receptor also involves mu opioid receptor of morphine and cannabinoid GPR55 receptors (other GPR receptors shown are also less known cannabinoid receptors) but also blood coagulation activating receptors. 
They have somewhat similar logic behind. Cannabinoids and opiates can create munchies for fatty foods and fatty foods can create blissful calm kinda similar to morphine. Blood coagulation probably depends on how fatty and viscous is blood already. Bradykinin widens blood vessels and lowers blood pressure. Maybe that bradykinin receptor started as a fatty acid sensor that widened blood vessels in case blood got too fatty and likely to clog up.
1 study that found that fatty foods activate coagulation in at least rats.  

NMDA glutamate receptors of fruit fly have similarities with human NMDA, kainate and AMPA glutamate receptors that work by letting positive ions into cells.

Serotonin receptor 1 "relatives" shown above are all stimulating to neurons. Results are kinda similar to serotonin like noradrenaline or dopamine plus 2 other serotonin receptors. Histamine and acetylcholine (M3 receptor) are also stimulatory substances in brain.

Nicotinic acetylcholine receptors (ion channel type) activate muscles during planned movements. One major similarity is with 5-HT3 receptor that is also ion channel and participates in diarrhea and vomiting during food poisoning.

Both images above are about  serotonin transporter that transports serotonin back to cells.   Other transport proteins have similar function. Second image is from the green triangle in first image. In addition to serotonin similar proteins also seem to work randomly with inhibitory (GABA, glycine) and excitatory (taurine, noradrenaline and dopamine) neurotransmitters.

Human oxytocin receptor similarities with fruit fly proteins. Second image is again expanded version of what's in the triangle on first image. Corazonin, octopamine and cardioacceleratory peptide are stimulatory neurotransmitters for invertebrate. CCK in humans causes nausea and anxiety. Tachykinin can activate human gut muscles. Adenosine seems to be only definitely inhibitory substance in that network. Gonadotropin-releasing hormone is needed in sexual maturity. Somatostatin inhibits release of growth hormones.
(I found mostly same receptors when i compared human CB1 with fruit fly receptors)

Opioid receptor from fruit fly larva had also many similarities with human receptors. All main human opioid (mu, kappa, delta, nociceptin) receptors were found. Orexin is needed to stay awake and lack of it or its receptors causes narcolepsy. Substance-P along with neurokinin are needed to transmit pain signals. Galanin is mostly inhibitory. Neuromedin U causes contraction of gut muscles. Serotonin 4 receptor showed up among opiate and gut motility receptors.

1 comment:

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