Serotonin-induced stereospecific formation and bioactivity of the eicosanoid 17,18-epoxyeicosatetraenoic acid in the regulation of pharyngeal pumping of C. elegans

Tools

Item Type:	Article
Title:	Serotonin-induced stereospecific formation and bioactivity of the eicosanoid 17,18-epoxyeicosatetraenoic acid in the regulation of pharyngeal pumping of C. elegans
Creators Name:	Zhou, Y., Rothe, M., Schunck, W.H., Ruess, L. and Menzel, R.
Abstract:	17,18-Epoxyeicosatetraenoic acid (17,18-EEQ), the most abundant eicosanoid generated by cytochrome P450 (CYP) enzymes in C. elegans, is a potential signaling molecule in the regulation of pharyngeal pumping activity of this nematode. As a chiral molecule, 17,18-EEQ can exist in two stereoisomers, the 17(R),18(S)- and 17(S),18(R)-EEQ enantiomers. Here we tested the hypothesis that 17,18-EEQ may function as a second messenger of the feeding-promoting neurotransmitter serotonin and stimulates pharyngeal pumping and food uptake in a stereospecific manner. Serotonin treatment of wildtype worms induced a more than twofold increase of free 17,18-EEQ levels. As revealed by chiral lipidomics analysis, this increase was almost exclusively due to an enhanced release of the (R,S)-enantiomer of 17,18-EEQ. In contrast to the wildtype strain, serotonin failed to induce 17,18-EEQ formation as well as to accelerate pharyngeal pumping in mutant strains defective in the serotonin SER-7 receptor. However, the pharyngeal activity of the ser-7 mutant remained fully responsive to exogenous 17,18-EEQ administration. Short term incubations of well-fed and starved wildtype nematodes showed that both racemic 17,18-EEQ and 17(R),18(S)-EEQ were able to increase pharyngeal pumping frequency and the uptake of fluorescence-labeled microspheres, while 17(S),18(R)-EEQ and also 17,18-dihydroxyeicosatetraenoic acid (17,18-DHEQ, the hydrolysis product of 17,18-EEQ) were ineffective. Taken together, these results show that serotonin induces 17,18-EEQ formation in C. elegans via the SER-7 receptor and that both the formation of this epoxyeicosanoid and its subsequent stimulatory effect on pharyngeal activity proceed with high stereospecificity confined to the (R,S)-enantiomer.
Keywords:	Caenorhabditis elegans Proteins, Cytochrome P-450 Enzyme System, Eicosanoids, Serotonin, Animals, Caenorhabditis elegans
Source:	Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
ISSN:	1388-1981
Publisher:	Elsevier
Volume:	1868
Number:	5
Page Range:	159304
Date:	May 2023
Official Publication:	https://doi.org/10.1016/j.bbalip.2023.159304
PubMed:	View item in PubMed

Repository Staff Only: item control page