FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3000390392> ?p ?o ?g. }

• W3000390392 endingPage "107474" @default.
• W3000390392 startingPage "107474" @default.
• W3000390392 abstract "Antagonists of the transient receptor potential vanilloid-1 (TRPV1) channel alter body temperature (Tb) in laboratory animals and humans: most cause hyperthermia; some produce hypothermia; and yet others have no effect. TRPV1 can be activated by capsaicin (CAP), protons (low pH), and heat. First-generation (polymodal) TRPV1 antagonists potently block all three TRPV1 activation modes. Second-generation (mode-selective) TRPV1 antagonists potently block channel activation by CAP, but exert different effects (e.g., potentiation, no effect, or low-potency inhibition) in the proton mode, heat mode, or both. Based on our earlier studies in rats, only one mode of TRPV1 activation – by protons – is involved in thermoregulatory responses to TRPV1 antagonists. In rats, compounds that potently block, potentiate, or have no effect on proton activation cause hyperthermia, hypothermia, or no effect on Tb, respectively. A Tb response occurs when a TRPV1 antagonist blocks (in case of hyperthermia) or potentiates (hypothermia) the tonic TRPV1 activation by protons somewhere in the trunk, perhaps in muscles, and – via the acido-antithermogenic and acido-antivasoconstrictor reflexes – modulates thermogenesis and skin vasoconstriction. In this work, we used a mathematical model to analyze Tb data from human clinical trials of TRPV1 antagonists. The analysis suggests that, in humans, the hyperthermic effect depends on the antagonist’s potency to block TRPV1 activation not only by protons, but also by heat, while the CAP activation mode is uninvolved. Whereas in rats TRPV1 drives thermoeffectors by mediating pH signals from the trunk, but not Tb signals, our analysis suggests that TRPV1 mediates both pH and thermal signals driving thermoregulation in humans. Hence, in humans (but not in rats), TRPV1 is likely to serve as a thermosensor of the thermoregulation system. We also conducted a meta-analysis of Tb data from human trials and found that polymodal TRPV1 antagonists (ABT-102, AZD1386, and V116517) increase Tb, whereas the mode-selective blocker NEO6860 does not. Several strategies of harnessing the thermoregulatory effects of TRPV1 antagonists in humans are discussed." @default.
• W3000390392 created "2020-01-23" @default.
• W3000390392 creator A5000284172 @default.
• W3000390392 creator A5001430902 @default.
• W3000390392 creator A5011770647 @default.
• W3000390392 creator A5020296645 @default.
• W3000390392 creator A5024587960 @default.
• W3000390392 creator A5028402941 @default.
• W3000390392 creator A5029371474 @default.
• W3000390392 creator A5034075321 @default.
• W3000390392 creator A5048753448 @default.
• W3000390392 creator A5054283357 @default.
• W3000390392 creator A5069043578 @default.
• W3000390392 creator A5071625120 @default.
• W3000390392 creator A5071885553 @default.
• W3000390392 creator A5072798669 @default.
• W3000390392 creator A5079229227 @default.
• W3000390392 date "2020-04-01" @default.
• W3000390392 modified "2023-10-06" @default.
• W3000390392 title "Hyperthermia induced by transient receptor potential vanilloid-1 (TRPV1) antagonists in human clinical trials: Insights from mathematical modeling and meta-analysis" @default.
• W3000390392 cites W1498475304 @default.
• W3000390392 cites W1499497249 @default.
• W3000390392 cites W1511198581 @default.
• W3000390392 cites W1521516049 @default.
• W3000390392 cites W1531868629 @default.
• W3000390392 cites W1539388364 @default.
• W3000390392 cites W1564377552 @default.
• W3000390392 cites W1571837352 @default.
• W3000390392 cites W1583791877 @default.
• W3000390392 cites W1594770614 @default.
• W3000390392 cites W1707413311 @default.
• W3000390392 cites W1774139972 @default.
• W3000390392 cites W1946202333 @default.
• W3000390392 cites W1964531781 @default.
• W3000390392 cites W1964925166 @default.
• W3000390392 cites W1965509871 @default.
• W3000390392 cites W1967323363 @default.
• W3000390392 cites W1971456679 @default.
• W3000390392 cites W1973796039 @default.
• W3000390392 cites W1975128387 @default.
• W3000390392 cites W1982011911 @default.
• W3000390392 cites W1982629087 @default.
• W3000390392 cites W1982659293 @default.
• W3000390392 cites W1984813271 @default.
• W3000390392 cites W1986693123 @default.
• W3000390392 cites W1988913062 @default.
• W3000390392 cites W1989749187 @default.
• W3000390392 cites W1990662303 @default.
• W3000390392 cites W1992358268 @default.
• W3000390392 cites W1994366534 @default.
• W3000390392 cites W1995920815 @default.
• W3000390392 cites W2002338746 @default.
• W3000390392 cites W2002498499 @default.
• W3000390392 cites W2003807776 @default.
• W3000390392 cites W2007034094 @default.
• W3000390392 cites W2009326432 @default.
• W3000390392 cites W2010180054 @default.
• W3000390392 cites W2014059835 @default.
• W3000390392 cites W2017946436 @default.
• W3000390392 cites W2022023122 @default.
• W3000390392 cites W2022332945 @default.
• W3000390392 cites W2023486326 @default.
• W3000390392 cites W2023811550 @default.
• W3000390392 cites W2026397955 @default.
• W3000390392 cites W2029342741 @default.
• W3000390392 cites W2029360579 @default.
• W3000390392 cites W2029834005 @default.
• W3000390392 cites W2031952894 @default.
• W3000390392 cites W2032339313 @default.
• W3000390392 cites W2033177142 @default.
• W3000390392 cites W2034407873 @default.
• W3000390392 cites W2034458389 @default.
• W3000390392 cites W2036313050 @default.
• W3000390392 cites W2037153938 @default.
• W3000390392 cites W2038066873 @default.
• W3000390392 cites W2039263844 @default.
• W3000390392 cites W2041185426 @default.
• W3000390392 cites W2042451060 @default.
• W3000390392 cites W204375293 @default.
• W3000390392 cites W2045566187 @default.
• W3000390392 cites W2046677990 @default.
• W3000390392 cites W2046955207 @default.
• W3000390392 cites W2047145433 @default.
• W3000390392 cites W2047169541 @default.
• W3000390392 cites W2048883209 @default.
• W3000390392 cites W2050749485 @default.
• W3000390392 cites W2050781058 @default.
• W3000390392 cites W2051684012 @default.
• W3000390392 cites W2054154138 @default.
• W3000390392 cites W2055335617 @default.
• W3000390392 cites W2055827598 @default.
• W3000390392 cites W2057681671 @default.
• W3000390392 cites W2058078905 @default.
• W3000390392 cites W2060136789 @default.
• W3000390392 cites W2067031434 @default.
• W3000390392 cites W2068168026 @default.
• W3000390392 cites W2072644682 @default.
• W3000390392 cites W2072890489 @default.

• next