nausea / vomiting, uremia, arginine - brief notes

Returning to my quest to understand the mechanisms of chronic nausea and vomiting, I revisited mirtazapine for cats. The main reason cats are prescribed Mirtz is for nausea and vomiting (NV) from azotemia or uremia due to chronic kidney disease, which older cats are prone to suffer. So which uremic toxins are implicated in NV?  Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA). 

~

SDMA has been found to be lower in women with ME/CFS:

https://www.frontiersin.org/articles/10.3389/fmed.2021.642710/full

hmmm ... so I guess this is not a cause of nausea in ME/CFS ...

more on related metabolic pathways in ME/CFS:

http://followmeindenmark.blogspot.com/2019/03/polyamines-5-methylthioadenosine-and.html

 ~

database entry on SDMA:

https://hmdb.ca/metabolites/HMDB0003334 

"Uremic syndrome may affect any part of the body and can cause nausea, vomiting, loss of appetite, and weight loss. This seems to be mediated by the direct binding or inhibition by uremic toxins of the enzyme NADPH oxidase (especially NOX4 which is abundant in the kidneys and heart) (A7868)."

~

 ADMA and SDMA are arginine derivatives and just recently I had read about lupus and canavanine, a toxic arginine analogue. Dysregulation of NO signalling? all three inhibit NOS.

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ADMA is elevated in hyperemesis gravidarum: https://link.springer.com/article/10.1007%2Fs00404-011-1982-y 

~ 


While reading more on ADMA and SDMA, I came across this on rapamycin:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764698/

"Among others, rapamycin stimulates CAT2B mRNA and protein expression in HUVECs resulting in increased L-arginine transport []. Several inflammatory cytokines (e.g., interleukin 4 and interleukin 10, interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) have been reported to stimulate expression and L-arginine transport in macrophages []. Moreover, TNF-α and supernatants of both Pseudomonas aeruginosa and Staphylococcus aureus also stimulate mRNA and protein expression of CAT2B and L-arginine influx in human corneal epithelial cells [], suggesting that under inflammatory conditions, cells with inducible CAT2B may increase L-arginine availability particularly for iNOS."

 

A Fragile X mouse model study of rapamycin did not go well, am wondering if increase in NO from iNOS was the problem.

 

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