Matches in SemOpenAlex for { <https://semopenalex.org/work/W4313857684> ?p ?o ?g. }
- W4313857684 endingPage "C587" @default.
- W4313857684 startingPage "C573" @default.
- W4313857684 abstract "The anthelmintic drug praziquantel (PZQ) causes contraction of parasitic schistosomes as well as constriction of blood vessels within the mesenteric vasculature of the host where the adult blood flukes reside. The contractile action of PZQ on the vasculature is mediated by the activation of host serotonergic 5-HT 2B receptors (5-HT 2B Rs). However, the molecular basis for PZQ interaction with these targets and the location of these 5-HT 2B receptors in the vessel wall have not been experimentally defined. Evaluation of a PZQ docking pose within the 5-HT 2B R orthosteric site, using both Ca 2+ reporter and bioluminescence resonance energy transfer (BRET) assays, identified residues F340 6.51 and F341 6.52 (transmembrane helix 6, TM6) as well as L209 EL2 (extracellular loop 2) as critical for PZQ-mediated agonist activity. A key determinant of PZQ selectivity for the 5-HT 2B receptor over the 5-HT 2A / 2C receptors was determined by M218 5.39 in transmembrane helix 5 (TM5) of the orthosteric site. Mutation of this residue to valine (M218V), as found in 5-HT 2A and 5-HT 2C , decreased PZQ agonist activity, whereas the reciprocal mutation (V215M) in 5-HT 2C increased PZQ activity. Two-photon imaging in intact mesenteric arterial strips visualized PZQ-evoked Ca 2+ transients within the smooth muscle cells of the vessel wall. PZQ also triggered cytoplasmic Ca 2+ signals in arterial smooth muscle cells in primary culture that were isolated from mesenteric blood vessels. These data define the molecular basis for PZQ action on 5-HT 2B receptors localized in vascular smooth muscle." @default.
- W4313857684 created "2023-01-10" @default.
- W4313857684 creator A5007335330 @default.
- W4313857684 creator A5023839040 @default.
- W4313857684 creator A5035289238 @default.
- W4313857684 creator A5049197736 @default.
- W4313857684 creator A5062737684 @default.
- W4313857684 creator A5074038972 @default.
- W4313857684 date "2023-02-01" @default.
- W4313857684 modified "2023-09-26" @default.
- W4313857684 title "Molecular and cellular basis of praziquantel action in the cardiovascular system" @default.
- W4313857684 cites W1978947246 @default.
- W4313857684 cites W1982847884 @default.
- W4313857684 cites W1990635904 @default.
- W4313857684 cites W2002036075 @default.
- W4313857684 cites W2005643237 @default.
- W4313857684 cites W2007486557 @default.
- W4313857684 cites W2008538276 @default.
- W4313857684 cites W2010597285 @default.
- W4313857684 cites W2011312787 @default.
- W4313857684 cites W2018117212 @default.
- W4313857684 cites W2036251618 @default.
- W4313857684 cites W2039836319 @default.
- W4313857684 cites W2047469406 @default.
- W4313857684 cites W2048688806 @default.
- W4313857684 cites W2057016079 @default.
- W4313857684 cites W2057541703 @default.
- W4313857684 cites W2065840120 @default.
- W4313857684 cites W2073293904 @default.
- W4313857684 cites W2078062108 @default.
- W4313857684 cites W2080347540 @default.
- W4313857684 cites W2109124630 @default.
- W4313857684 cites W2114532320 @default.
- W4313857684 cites W2114650590 @default.
- W4313857684 cites W2133402952 @default.
- W4313857684 cites W2147156557 @default.
- W4313857684 cites W2157135620 @default.
- W4313857684 cites W2163161835 @default.
- W4313857684 cites W2171144789 @default.
- W4313857684 cites W2171400387 @default.
- W4313857684 cites W2200015442 @default.
- W4313857684 cites W2560664924 @default.
- W4313857684 cites W2581696375 @default.
- W4313857684 cites W2770931274 @default.
- W4313857684 cites W2884011290 @default.
- W4313857684 cites W2967702639 @default.
- W4313857684 cites W2982250586 @default.
- W4313857684 cites W2982809992 @default.
- W4313857684 cites W2989563826 @default.
- W4313857684 cites W3022812876 @default.
- W4313857684 cites W3119647775 @default.
- W4313857684 cites W4211093028 @default.
- W4313857684 cites W4211128418 @default.
- W4313857684 cites W4211145066 @default.
- W4313857684 cites W4225873156 @default.
- W4313857684 cites W4313251268 @default.
- W4313857684 cites W2427150327 @default.
- W4313857684 doi "https://doi.org/10.1152/ajpcell.00520.2022" @default.
- W4313857684 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36622066" @default.
- W4313857684 hasPublicationYear "2023" @default.
- W4313857684 type Work @default.
- W4313857684 citedByCount "2" @default.
- W4313857684 countsByYear W43138576842023 @default.
- W4313857684 crossrefType "journal-article" @default.
- W4313857684 hasAuthorship W4313857684A5007335330 @default.
- W4313857684 hasAuthorship W4313857684A5023839040 @default.
- W4313857684 hasAuthorship W4313857684A5035289238 @default.
- W4313857684 hasAuthorship W4313857684A5049197736 @default.
- W4313857684 hasAuthorship W4313857684A5062737684 @default.
- W4313857684 hasAuthorship W4313857684A5074038972 @default.
- W4313857684 hasConcept C118892022 @default.
- W4313857684 hasConcept C12554922 @default.
- W4313857684 hasConcept C135285700 @default.
- W4313857684 hasConcept C170493617 @default.
- W4313857684 hasConcept C185592680 @default.
- W4313857684 hasConcept C2778938600 @default.
- W4313857684 hasConcept C55493867 @default.
- W4313857684 hasConcept C86803240 @default.
- W4313857684 hasConcept C95444343 @default.
- W4313857684 hasConcept C98274493 @default.
- W4313857684 hasConceptScore W4313857684C118892022 @default.
- W4313857684 hasConceptScore W4313857684C12554922 @default.
- W4313857684 hasConceptScore W4313857684C135285700 @default.
- W4313857684 hasConceptScore W4313857684C170493617 @default.
- W4313857684 hasConceptScore W4313857684C185592680 @default.
- W4313857684 hasConceptScore W4313857684C2778938600 @default.
- W4313857684 hasConceptScore W4313857684C55493867 @default.
- W4313857684 hasConceptScore W4313857684C86803240 @default.
- W4313857684 hasConceptScore W4313857684C95444343 @default.
- W4313857684 hasConceptScore W4313857684C98274493 @default.
- W4313857684 hasFunder F4320310846 @default.
- W4313857684 hasFunder F4320334173 @default.
- W4313857684 hasFunder F4320337338 @default.
- W4313857684 hasFunder F4320337354 @default.
- W4313857684 hasFunder F4320337355 @default.
- W4313857684 hasIssue "2" @default.
- W4313857684 hasLocation W43138576841 @default.
- W4313857684 hasLocation W43138576842 @default.