Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
Volume 1868, Issue 5, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.bbalip.2023.159304
Keywords
17; 18-EEQ; Eicosanoids; Stereoisomers; Chiral phase; Caenorhabditis elegans; Pharynx
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17,18-Epoxyeicosatetraenoic acid (17,18-EEQ) is a potential signaling molecule in regulating the pharyngeal pumping activity of C. elegans. Serotonin induces the formation of 17,18-EEQ via the SER-7 receptor, and stimulation of pharyngeal activity by 17,18-EEQ is highly stereospecific to the (R,S)-enantiomer. These findings suggest that 17,18-EEQ may function as a second messenger of serotonin in promoting feeding behavior.
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 ste-reospecific 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.
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