| Autor: |
Fears LS; Department of Biological Sciences, Tennessee State University, United States of America., Curtis ME; Department of Biological Sciences, Tennessee State University, United States of America., Johnson TL; Department of Biological Sciences, Tennessee State University, United States of America., Fentress HM; Department of Biological Sciences, Tennessee State University, United States of America. |
| Jazyk: |
angličtina |
| Zdroj: |
EC pharmacology and toxicology [EC Pharmacol Toxicol] 2019 Jan 29; Vol. 30 (Suppl 1), pp. 103-111. Date of Electronic Publication: 2016 Apr 01. |
| Abstrakt: |
The monoamine neurotransmitter serotonin (5-HT) plays a role in many physiological responses by interacting with various receptor subtypes. The 5-HT 2C receptor subtype is a 7-transmembrane, G protein-coupled receptor (GPCR) that is involved in neuronal excitability, spatial learning, mood, and appetite. The microorganism Chromobacterium violaceum produces a purple pigment, violacein, which can be extracted and purified. Violacein has antibiotic, antileishmanial, antifungal and antitumoral properties in various cancer cell lines. Violacein is derived from the amino acid tryptophan as is 5-HT and therefore, the two have similar chemical structures. However, no one has reported the activity of violacein at 5-HT receptors. Therefore the Fentress lab decided to investigate whether or not violacein had an effect on 5-HT 2C receptor trafficking. Human Embryonic Kidney (HEK) 293 cells expressing fluorescently-tagged 5-HT 2C receptor were treated with 5-HT, violacein, water or vehicle and then cells were fixed and visualized with fluorescent microscopy. Violacein treatment did not cause receptor internalization. Recent studies suggest that the 5-HT 2C receptor can activate the JAK/STAT pathway. To see if violacein can modulate this pathway, HEK 293 cells expressing 5-HT 2C receptor were treated with either 5-HT, violacein, or pretreated with violacein followed by incubation with 5-HT. Phosphorylation states of JAK2 and STAT3 were examined by immunoblotting. Results determined that 5-HT 2C receptor activation had no effect on JAK2 phosphorylation and that violacein blocked STAT3 phosphorylation. Primary radioligand binding determined that violacein has a low affinity for 5-HT 2C receptor but has a higher affinity for adrenergic receptors. Future studies will examine G protein-coupling by measuring phosphoinositide hydrolysis and cAMP assay to investigate adrenergic pathways.
Competing Interests: Conflict of Interest There are no conflicts of interest. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
