FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3136283867> ?p ?o ?g. }

• W3136283867 endingPage "3916" @default.
• W3136283867 startingPage "3900" @default.
• W3136283867 abstract "Understanding the sensory mechanisms innervating the bladder is paramount to developing efficacious treatments for chronic bladder hypersensitivity conditions. The contribution of Mas-gene-related G protein-coupled receptors (Mrgpr) to bladder signaling is currently unknown. Using male and female mice, we show with single-cell RT-PCR that subpopulations of DRG neurons innervating the mouse bladder express MrgprA3 (14%) and MrgprC11 (38%), either individually or in combination, with high levels of coexpression with Trpv1 (81%-89%). Calcium imaging studies demonstrated MrgprA3 and MrgprC11 agonists (chloroquine, BAM8-22, and neuropeptide FF) activated subpopulations of bladder-innervating DRG neurons, showing functional evidence of coexpression between MrgprA3, MrgprC11, and TRPV1. In ex vivo bladder-nerve preparations, chloroquine, BAM8-22, and neuropeptide FF all evoked mechanical hypersensitivity in subpopulations (20%-41%) of bladder afferents. These effects were absent in recordings from Mrgpr-cluster Δ −/− mice. In vitro whole-cell patch-clamp recordings showed that application of an MrgprA3/C11 agonist mixture induced neuronal hyperexcitability in 44% of bladder-innervating DRG neurons. Finally, in vivo instillation of an MrgprA3/C11 agonist mixture into the bladder of WT mice induced a significant activation of dorsal horn neurons within the lumbosacral spinal cord, as quantified by pERK immunoreactivity. This MrgprA3/C11 agonist-induced activation was particularly apparent within the superficial dorsal horn and the sacral parasympathetic nuclei of WT, but not Mrgpr-cluster Δ −/− mice. This study demonstrates, for the first time, functional expression of MrgprA3 and MrgprC11 in bladder afferents. Activation of these receptors triggers hypersensitivity to distension, a critically valuable factor for therapeutic target development. SIGNIFICANCE STATEMENT Determining how bladder afferents become sensitized is the first step in finding effective treatments for common urological disorders such as overactive bladder and interstitial cystitis/bladder pain syndrome. Here we show that two of the key receptors, MrgprA3 and MrgprC11, that mediate itch from the skin are also expressed on afferents innervating the bladder. Activation of these receptors results in sensitization of bladder afferents, resulting in sensory signals being sent into the spinal cord that prematurely indicate bladder fullness. Targeting bladder afferents expressing MrgprA3 or MrgprC11 and preventing their sensitization may provide a novel approach for treating overactive bladder and interstitial cystitis/bladder pain syndrome." @default.
• W3136283867 created "2021-03-29" @default.
• W3136283867 creator A5001046498 @default.
• W3136283867 creator A5017270578 @default.
• W3136283867 creator A5034642885 @default.
• W3136283867 creator A5048849206 @default.
• W3136283867 creator A5054558614 @default.
• W3136283867 creator A5056756113 @default.
• W3136283867 creator A5066126497 @default.
• W3136283867 creator A5077412647 @default.
• W3136283867 creator A5087216741 @default.
• W3136283867 date "2021-03-16" @default.
• W3136283867 modified "2023-10-15" @default.
• W3136283867 title "Activation of MrgprA3 and MrgprC11 on Bladder-Innervating Afferents Induces Peripheral and Central Hypersensitivity to Bladder Distension" @default.
• W3136283867 cites W1006559644 @default.
• W3136283867 cites W1490106730 @default.
• W3136283867 cites W1502228150 @default.
• W3136283867 cites W1590044823 @default.
• W3136283867 cites W1928649034 @default.
• W3136283867 cites W1962557443 @default.
• W3136283867 cites W1965018866 @default.
• W3136283867 cites W1967312126 @default.
• W3136283867 cites W1969655931 @default.
• W3136283867 cites W1982134608 @default.
• W3136283867 cites W1988631520 @default.
• W3136283867 cites W2018745308 @default.
• W3136283867 cites W2022279793 @default.
• W3136283867 cites W2023309742 @default.
• W3136283867 cites W2033072655 @default.
• W3136283867 cites W2056514314 @default.
• W3136283867 cites W2059635921 @default.
• W3136283867 cites W2064267093 @default.
• W3136283867 cites W2070056663 @default.
• W3136283867 cites W2083566192 @default.
• W3136283867 cites W2087004322 @default.
• W3136283867 cites W2087082823 @default.
• W3136283867 cites W2092553043 @default.
• W3136283867 cites W2096191613 @default.
• W3136283867 cites W2107270966 @default.
• W3136283867 cites W2108328978 @default.
• W3136283867 cites W2118866905 @default.
• W3136283867 cites W2123046464 @default.
• W3136283867 cites W2123491442 @default.
• W3136283867 cites W2131363903 @default.
• W3136283867 cites W2134966330 @default.
• W3136283867 cites W2139416059 @default.
• W3136283867 cites W2140167700 @default.
• W3136283867 cites W2153762549 @default.
• W3136283867 cites W2157856809 @default.
• W3136283867 cites W2188528980 @default.
• W3136283867 cites W2203163745 @default.
• W3136283867 cites W2275270272 @default.
• W3136283867 cites W2397623070 @default.
• W3136283867 cites W2409924309 @default.
• W3136283867 cites W2507750318 @default.
• W3136283867 cites W2589845804 @default.
• W3136283867 cites W2616031810 @default.
• W3136283867 cites W2658508676 @default.
• W3136283867 cites W2769601261 @default.
• W3136283867 cites W2774300852 @default.
• W3136283867 cites W2797149985 @default.
• W3136283867 cites W2808171445 @default.
• W3136283867 cites W2884812951 @default.
• W3136283867 cites W2889506939 @default.
• W3136283867 cites W2894650121 @default.
• W3136283867 cites W2903933553 @default.
• W3136283867 cites W2905429510 @default.
• W3136283867 cites W2911591117 @default.
• W3136283867 cites W2936303415 @default.
• W3136283867 cites W2944842967 @default.
• W3136283867 cites W2946176530 @default.
• W3136283867 cites W2951381321 @default.
• W3136283867 cites W2964591612 @default.
• W3136283867 cites W2972124338 @default.
• W3136283867 cites W2972311952 @default.
• W3136283867 cites W2974548772 @default.
• W3136283867 cites W2990341499 @default.
• W3136283867 cites W3015493096 @default.
• W3136283867 cites W3025513652 @default.
• W3136283867 cites W3058138249 @default.
• W3136283867 cites W310346613 @default.
• W3136283867 cites W341973698 @default.
• W3136283867 cites W4249317513 @default.
• W3136283867 doi "https://doi.org/10.1523/jneurosci.0033-21.2021" @default.
• W3136283867 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8084315" @default.
• W3136283867 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33727332" @default.
• W3136283867 hasPublicationYear "2021" @default.
• W3136283867 type Work @default.
• W3136283867 sameAs 3136283867 @default.
• W3136283867 citedByCount "8" @default.
• W3136283867 countsByYear W31362838672021 @default.
• W3136283867 countsByYear W31362838672022 @default.
• W3136283867 countsByYear W31362838672023 @default.
• W3136283867 crossrefType "journal-article" @default.
• W3136283867 hasAuthorship W3136283867A5001046498 @default.
• W3136283867 hasAuthorship W3136283867A5017270578 @default.
• W3136283867 hasAuthorship W3136283867A5034642885 @default.
• W3136283867 hasAuthorship W3136283867A5048849206 @default.

• next