Hi Sunil,

There is a closely related discussion here;

https://www.researchgate.net/post/How_do_serotonin_and_dopamine_interact?pli=1&loginT=6V44bUHGwd-BJObGSf8TaA3Ft8qmA66mebVHLyLaqkw*&uid=7a79ad6a-d46e-435e-be11-51f8a9dec272&cp=re221_es_d_en_e1_p42&ch=reg

.

Regards,

Paul.

This paper gives more information:

Psychopharmacology (Berl). 2014 Aug 14. Safety, pharmacokinetic, and positron emission tomography evaluation of serotonin and dopamine transporter occupancy following multiple-dose administration of the triple monoamine reuptake inhibitor BMS-820836. Zheng M et al.

Dear Paul,

Thanks for pointing out to interesting discussion about DA and 5HT interactions, but I am looking for some information about how the transporters (DAT for DA and SERT for 5-HT) of these major neurotransmitters coordinates with each other to maintain the chemical equilibrium in extracellular space without warranting the integrity of the cell. Thanks for your comments and suggestions.  

Without doing a systematic literature search and analysis, it seems unlikely that there are mechanisms that permit the co-ordinated regulation of SERT and DAT activity in the short term. Certainly there are interacting proteins that may well influence the activity of each transporter, but these are intracellular and thus it wold be difficult to envisage a mechanism whereby both transporters are influenced in a co-ordinated way. Thus I would suggest that 

(it seems they system is not acceping longer answers!)

... that longer-term regulation could occur via common transcriptional regulatory mechanisms and 

sod it, I give up...

Regulation of Monoamine Transporters: Role of Transporter Phosphorylation

Sammanda Ramamoorthy, Toni S. Shippenberg, Lankupalle D. Jayanthi

Pharmacol Ther. Author manuscript; available in PMC 2012 February 1.Published in final edited form as: Pharmacol Ther. 2011 February; 129(2): 220–238. Published online 2010 October 15. doi: 10.1016/j.pharmthera.2010.09.009

Dear Gavin,

Thanks for your comments, I see your point that it may be some of the common transcription factors playing role in synthesis of these transporters. So, do you think that even (if) they are sharing the common domains at the transcription level and may change at the translation level which leads their functional mechanism to operate in two independent pathways or they coordinates with each other by using some indirect or direct mechanisms to maintained the normal cellular function? Thanks again for your valuable comments

Dear Sunil,

Various kinases have been linked to DAT regulation including PKA, PKC, PI-3K, ERK, ERK, Akt, CaMKII, CDK, and MAPK.

Regulation of SERT has been linked to acute depletion of intracellular Ca Na 2+, calmodulin inhibition, CaMKII, Src, p38 MAP kinase, PKC, and activation of NOS/cGMP

Perhaps Gavin can explain this.

Dear Beatrice,

Thanks for sending the links of some very useful articles and comments. This is interesting that both of these transporters regulated by some of the common enzymes. There are some evidence about the interaction between SERT and DAT genes and their role on regulating the behavior like: negative valence and emotional belief biased suppression and suggest that carriers of both risk alleles: SERT and DAT1 controls the negative emotional reactivity and have significant role in higher belief bias emotional reactivity. So if both of these transporters sharing the common risk alleles, then there might a interaction between these transporters at the functional level which might be playing a important role in maintaining the normal function of the cell. Thanks again for your input.

Thought I would chime in here.  To my knowledge (and I may be missing some new literature here), DAT and SERT are not expressed on the same neurons.  Dopamine neurons use DAT for the re-uptake of DA, while 5HT neurons use SERT.  There have been some great articles about co-release of GABA with dopamine using VMAT as the vesicular transporter but, to my knowledge DAT and SERT do not occupy the same space.  In terms of regulation, G-protein coupled auto receptors monitor the extracellular levels of DA or 5HT and signal inside the cell to alter surface expression of DAT or SERT (depending on the signal).  So in terms of how these transports alter extracellular concentrations can be found there.  How they work in concert (i.e. does DA concentrations somehow affect SERT activity) I'm not sure has been established.  

Hi Paul,

Thanks for your comments and input to the questions. Yes indeed, DAT and SERT expressed in different type of neurons and that's why they are named based on the type of neurons. But, there are evidences showing  some type of interaction between these transporters, for example, both transporters interact with nNOS which can influence their function and can decrease or increase the extracellular availability of dopamine or serotonin and modulate the behavior. So I am trying to find out that, is there any harmony between these transporters at the function level to maintain the ionic concentration in extracellular space or they completely regulating two independent pathways.

Thanks again for your input and sharing your valuable thoughts and views about it

Gotcha... I'm sure there are conserved signaling mechanisms that may influence their membrane availability (as well as non-conserved DAT/SERT specific signaling).  I guess the word that was throwing me off was "interaction." As a molecular biologist my mind goes directly to either protein-protein interaction, or a "direct" interaction based on upstream signaling that might allow for differential expression of either (in the same cell).  While there may be some conservation of mechanism of regulation, I don't think there is any kind of direct "cross-talk" if you will.. just my thoughts.

I think there might be a synergistic or antagonistic interaction between serotonergic and dopaminergic neurons. In schizophrenia 5-HT2A serotonergic and D2 dopaminergic neurons have a hyperactivity in the mesolimbic system and the hippocampus. SGA's mostly have a D2 and 5-HT2A antagonistic effect and are more efficacious than FGS's, which only interfere with D2 receptors. In the extrapyramidal system, e.g. in the putamen, 5-HT2A serotonergic and D2 dopaminergic neurons have an antagonistic interaction as I described in an article, to be published in the Journal of Cytology & Histology. I derived my findings from experimental works.

Hi Werner,

Thanks so much for your comments about the probability of synergistic interaction between SERT and DAT, very interesting!. Can you please send me the article 5-HT2A and D2 interactions once it get published. This might be very useful information for looking at interaction between these transporters. If these transporters sharing some common domains at active site then these both should respond to the same agonist or antagonist

Thanks again!!

Hi Sunil, the article can be found under my publication: Schizophrenia: from the genetic localization to the cellular mechanism. The interaction between D2 dopaminergic and 5-HT2A serotonergic neurons in the extrapyramidal system can found under Omics Publishing Ltd.: Classical neurotransmitters and neuropeptides involved in Parkinson's disease: a multi-neurotransmitter system. Kind regards, F.-M. Werner

Dear Werner,

Thanks so much for the information about these articles, these are really nice article about the network level understanding of the neurotransmitters and their receptors.

Thanks again!! 

Hi guys, I am also exploring the interplay between dopamine and serotonin, hoping to draw parallels with surfing; whereby dopamine equates to the surfboard, and serotonin to the wave. Basically, the positive and negative symptoms associated with each neurotransmitter can be likened to wave shape and surfboard design, insofar as the bathymetry of a surf break determines how abruptly the waves break, while the shape of the surfboard determines how rapidly it responds to the surfer's movements. My hope is to find evidence of an interplay between dopamine and serotonin, which could somehow parallel the interplay - between surfboard design and wave shape - that optimises (or distrupts) surfing performance.

For example, Bédard, et al. (2011) suggest that an increase in striatial 5-HT innervation among patients with Parkinson's "might be the result of a neural mechanism designed to compensate for DA denervation", adding that; "These findings underline the importance of the complex interplay between DA and 5-HT striatal afferents in the elaboration of appropriate motor behaviour."

This could be likened to a surfer choosing to surf slow moving waves because they are better suited to his slow moving surfboard; the way longboarders prefer waves that are not too demanding.

I would be 'stoked' if you could give some consideration to the surfing analogy.

Thanks!

And Happy Xmas.

Regards, Dan

"dopamine equates to the surfboard, and serotonin to the wave. Basically, the positive and negative symptoms associated with each neurotransmitter can be likened to wave shape and surfboard design, insofar as the bathymetry of a surf break determines how abruptly the waves break, while the shape of the surfboard determines how rapidly it responds to the surfer's movements"

Brilliant! What does stoke mean?

Stoked is surf vernacular for overjoyed, elated, thrilled, etc.

Thanks for the thumbs up!