How to activate mast cells: Receptors and Ligands Master Table (part 3)

Receptor Ligand (molecules that bind to the receptor) Result
Nicotinic acetylcholine receptor Acetylcholine Increases severity of anaphylaxis
NOD1, NOD2 Bacterial products Cytokines; dependent upon ligand
Paired Ig-like receptor B (PIR-B) Inhibitory
Peripheral benzodiazepine receptor Benzodiazepines Inhibits mediator release
Platelet endothelial cell adhesion molecule (PECAM-1) Inhibitory
Progesterone receptor Progesterone Inhibits mediator release
Prostaglandin E receptors, EP2, Prostaglandin E Downregulates IgE mediated response, inhibits prostaglandin and leukotriene production


Prostaglandin E receptors, EP3, EP4 Prostaglandin E Increases IgE mediated degranulation : histamine, tryptase, carboxypeptide, chymase, heparin, chondroitin


Increases IgE dependent cytokine production


Protease activated receptors 1-4 (PAR1-4) Serine proteases (trypsin, tryptase, chymase) Histamine release, mast cell activation
Purinoreceptor P2Y11 ATP Production of prostaglandins and leukotrienes
Purinoreceptor P2Y2 ATP, UTP Production of prostaglandins and leukotrienes
Purinoreceptors P2Y1, P2Y12, P2Y13 ADP Production of prostaglandins and leukotrienes
Sialic acid binding Inhibitory
Sphingosine-1-phosphate S1P1 Sphingosine-1-phosphate Chemotaxis


Sphingosine-1-phosphate S1P2 Sphingosine-1-phosphate Degranulation : histamine, tryptase, carboxypeptide, chymase, heparin, chondroitin


De novo:
IL-3, IL-4, IL-5 IL-6, IL-8, IL-10, IL-13, TNF, GM-CSF, CCL2, CCL3, CCL5


ST2 IL-33 Cytokines
TGFb receptor 1 TGFb Decreases IgE dependent degranulation, IgE dependent TNF production
TLR1-9 Bacterial and viral products Cytokines ; dependent upon ligand
Urokinase receptor Urokinase Movement of mast cells
Vitamin D receptor Vitamin D Mast cell development
β2-adrenoreceptor Adrenaline Inhibits FcεRI degranulation and cytokine production and secretion

13 Responses

  1. Jan Hempstead August 17, 2015 / 5:33 am

    Thank you for your very thorough list. Can you list your source specifically for the benzodiazepine receptors and inhibition of mediators? There seems to be some differences amongst physicians regarding this. It would be great to bring them the scientific data.
    Thanks! Jan

    • Lisa Klimas August 17, 2015 / 9:42 am

      This table was for my own quick reference and I didn’t record all the references. I mentioned this in the first post of this series.

  2. Jan Hempstead August 17, 2015 / 10:21 am

    Okay thanks Lisa. I’m trying to find something evidence-based to bring to my physician who states it’s only for anxiety, it does not help mast cells in any way except to keep us calm because stress/anxiety is a trigger.

  3. Lynn August 29, 2015 / 10:58 am

    Wow, this is really interesting and wondering so many ways to cause reactions!?
    Vitamin D can cause reaction?
    Had about 5 people tell me to get checked for some mast cell thing and wondering what to
    Dont do well with 2 antihistamines tried (fall asleep rest of day), onions and fresh ginger work for me as antihistamine. Think might have related to saliculates and when lower those, feel better. Wonder if can track by symptm if leukotrines or cytokines, histamines…. (heard cucmber is good for leukotrine reactions) then reduce those and increase foods that help, but see there are so many possible instigators depending on each person.
    Would Really like to be more human again (not zombie/brain ) or go out when is so hot (90-100’s) . Thank you LIsa for this info, will try scanning rest as computer and brain and time allow. This week am guessing low BP from heat, also notice worse around computer (so EMF).

    • Lisa Klimas August 29, 2015 / 10:25 pm

      The role of vitamin D in mast cell behavior is still being elucidated. It is known to influence mast cell life and differentiation, but beyond that (whether or not it causes reactions) is less clear. The chemicals released can cause a number of symptoms and there is a lot of overlap, it is rarely the fault of only one mediator. Feel better! Hoping for cooler days here also.

  4. Charlotte January 2, 2016 / 12:23 pm

    Dear Lisa,
    Thank you for the precious work you do, and may I wish for a specific subject? 🙂

    Could you dig a little deeper on the vitamin D levels and how it effects mast cell maturation?
    I saw a paper not so long ago that high 1,25 D could depress tryptase levels, for exampel, and I also seen papers talking about how 1,25 D could disturb the maturation of mast cells so that they became too sensitive, or behave differently. I have the VDR Bsm genetic variant that are supposed to predict for higher 1,25 levels. SM has been ruled out by our local doctors, but I strongly suspect MCAS and knowledge is lacking here.
    I would be wonderful if you could sum up what has been written about these things. You mentioned that low levels of 25 D is often seen in MCAS, and mine are very low but I have too high levels of 1,25 D in my blood, and also low tryptase.

    Here is one of the papers I have stumbled upon;

    VDR-dependent regulation of mast cell maturation mediated by 1,25-dihydroxyvitamin D3

    • Lisa Klimas January 2, 2016 / 10:04 pm

      Sure. I’ll add it to my list. 🙂

  5. Charlotte February 1, 2016 / 9:36 am

    Hi! How is the collection of studies going? 🙂 😉
    There is one more thing I would like to add, and that is the possibility that the VDR is not able to be so well activated by 1,25 D, if it is disabled by either pathogens or maybe genetics.
    In vivo test results might be different from in vitro tests due to this aspect, if there is no contamination and a proper and normal VDR function. I think those two aspects are important. To add 1,25 D in vivo migh not at all have the same effect as in vitro VDR, and conclusions cannot been drawn from in vitro. And of course, human VDR function are not similar to mice or rats when it comes to what kind of chain reactions it starts. 🙂

    • Lisa Klimas February 1, 2016 / 10:44 am

      I’m sorry? I currently have a list of requests that is about 250 entries long, all of which require research. Vitamin D is on my list, but it will be a bit before I get to it.

  6. Charlotte February 2, 2016 / 6:18 am

    No no, do not be sorry, I am sorry. I did not mean to put pressure on you, I just wanted to add that aspect, and then let go of it, so take all the time you need, it is yours.
    I just did not want to forget to add that, since I see that in some papers there seem to be conclusions that vitamin D would be a good thing to add, for anybody, and that is not the conclusion one should make. Too high levels of 1,25D are a risk for how mast cells mature, and it could be that high levels are is very common in this time of extremely high supplementation of Vitamin D. It might be an explaination to why MCAS seem to be more common now. So, no stress at all, I do my own research, I just wanted to hear your input in this, in time. 🙂

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