Serotonin 2A (5-HT2A) is a GPCR expressed in the cortex, hippocampus, and gastrointestinal tract, vascular smooth muscle cells, platelets among others. It is associated with learning, memory, mood regulation, platelet aggregation, and vasoconstriction, but its involvement in cell substrate adhesion remained unknown. Here we report a novel role for serotonin and 5-HT2A in cell-matrix adhesion. In the present study, we show adhesion-related processes to be affected by serotonin in HEK293 cells and mouse cortices.
In HEK293 cells, which are loosely adherent, expression and stimulation of human or rat 5-HT2A receptor led to an increase in adhesion by serotonin. In these cells, treatment with agonists such as serotonin, DA or 2,5-dimethoxy-4-iodoamphetamine (DOI) led to a significant increase in adhesion while inhibition of 5-HT2A by antipsychotics and antidepressants, such as risperidone, olanzapine, chlorpromazine, clozapine, and haloperidol. 5-HT2A activation was necessary for the formation and maintenance of stress fibers in these cells, and the mechanism of 5-HT2A-mediated adhesion in HEK293 cells was dependent on the activation of PKC and Rho.
Using DNA microarrays and RNA extracted from the cortices of 5-HT2A (-/-) and 5-HT2A (+/+) mice we see several adhesion-related genes to be downregulated in 5-HT2A (-/-) and several neurite-associated genes to be differentially regulated. This could clearly be one of the first in vivo correlate of novel finding of 5-HT2A mediated adhesion.
These observations have obvious implications in understanding neuronal circuit formation, synaptic adhesion, disease progression in neuronal disorders and medications that target these processes. Since more than 90% of serotonin is present in the periphery, serotonin/5-HT2A could perhaps play a major role in other adhesion-related roles for e.g. atherosclerosis, fibrosis, in immune cells, development and homeostasis. In the light of the above results, it could also be tempting to speculate that in Covid-19 associated coagulopathy.
Reference: John Jayakumar, J. A. K., Panicker, M. M., & Basu, B. (2020). Serotonin 2A (5-HT 2A) receptor affects cell–matrix adhesion and the formation and maintenance of stress fibers in HEK293 cells. Scientific Reports, 10(1), 1–14.
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