Citation
Thorneloe, Kevin S., et al. "N-((1S)-1-{[4-((2S)-2-{[(2,4-dichlorophenyl)sulfonyl]amino}-3-hydroxypropanoyl)-1-piperazinyl]carbonyl}-3-methylbutyl)-1-benzothiophene-2-carboxamide (GSK1016790A), a Novel and Potent Transient Receptor Potential Vanilloid 4 Channel Agonist Induces Urinary Bladder Contraction and Hyperactivity: Part I." The Journal of Pharmacology and Experimental Therapeutics, vol. 326, no. 2, 2008, pp. 432-42.
Thorneloe KS, Sulpizio AC, Lin Z, et al. N-((1S)-1-{[4-((2S)-2-{[(2,4-dichlorophenyl)sulfonyl]amino}-3-hydroxypropanoyl)-1-piperazinyl]carbonyl}-3-methylbutyl)-1-benzothiophene-2-carboxamide (GSK1016790A), a novel and potent transient receptor potential vanilloid 4 channel agonist induces urinary bladder contraction and hyperactivity: Part I. J Pharmacol Exp Ther. 2008;326(2):432-42.
Thorneloe, K. S., Sulpizio, A. C., Lin, Z., Figueroa, D. J., Clouse, A. K., McCafferty, G. P., Chendrimada, T. P., Lashinger, E. S., Gordon, E., Evans, L., Misajet, B. A., Demarini, D. J., Nation, J. H., Casillas, L. N., Marquis, R. W., Votta, B. J., Sheardown, S. A., Xu, X., Brooks, D. P., ... Westfall, T. D. (2008). N-((1S)-1-{[4-((2S)-2-{[(2,4-dichlorophenyl)sulfonyl]amino}-3-hydroxypropanoyl)-1-piperazinyl]carbonyl}-3-methylbutyl)-1-benzothiophene-2-carboxamide (GSK1016790A), a novel and potent transient receptor potential vanilloid 4 channel agonist induces urinary bladder contraction and hyperactivity: Part I. The Journal of Pharmacology and Experimental Therapeutics, 326(2), 432-42. https://doi.org/10.1124/jpet.108.139295
Thorneloe KS, et al. N-((1S)-1-{[4-((2S)-2-{[(2,4-dichlorophenyl)sulfonyl]amino}-3-hydroxypropanoyl)-1-piperazinyl]carbonyl}-3-methylbutyl)-1-benzothiophene-2-carboxamide (GSK1016790A), a Novel and Potent Transient Receptor Potential Vanilloid 4 Channel Agonist Induces Urinary Bladder Contraction and Hyperactivity: Part I. J Pharmacol Exp Ther. 2008;326(2):432-42. PubMed PMID: 18499743.
TY - JOUR
T1 - N-((1S)-1-{[4-((2S)-2-{[(2,4-dichlorophenyl)sulfonyl]amino}-3-hydroxypropanoyl)-1-piperazinyl]carbonyl}-3-methylbutyl)-1-benzothiophene-2-carboxamide (GSK1016790A), a novel and potent transient receptor potential vanilloid 4 channel agonist induces urinary bladder contraction and hyperactivity: Part I.
AU - Thorneloe,Kevin S,
AU - Sulpizio,Anthony C,
AU - Lin,Zuojun,
AU - Figueroa,David J,
AU - Clouse,Angela K,
AU - McCafferty,Gerald P,
AU - Chendrimada,Tim P,
AU - Lashinger,Erin S R,
AU - Gordon,Earl,
AU - Evans,Louise,
AU - Misajet,Blake A,
AU - Demarini,Douglas J,
AU - Nation,Josephine H,
AU - Casillas,Linda N,
AU - Marquis,Robert W,
AU - Votta,Bartholomew J,
AU - Sheardown,Steven A,
AU - Xu,Xiaoping,
AU - Brooks,David P,
AU - Laping,Nicholas J,
AU - Westfall,Timothy D,
Y1 - 2008/05/22/
PY - 2008/5/24/pubmed
PY - 2008/8/13/medline
PY - 2008/5/24/entrez
SP - 432
EP - 42
JF - The Journal of pharmacology and experimental therapeutics
JO - J Pharmacol Exp Ther
VL - 326
IS - 2
N2 - The transient receptor potential (TRP) vanilloid 4 (TRPV4) member of the TRP superfamily has recently been implicated in numerous physiological processes. In this study, we describe a small molecule TRPV4 channel activator, (N-((1S)-1-{[4-((2S)-2-{[(2,4-dichlorophenyl)sulfonyl]amino}-3-hydroxypropanoyl)-1-piperazinyl]carbonyl}-3-methylbutyl)-1-benzothiophene-2-carboxamide (GSK1016790A), which we have used as a valuable tool in investigating the role of TRPV4 in the urinary bladder. GSK1016790A elicited Ca2+ influx in mouse and human TRPV4-expressing human embryonic kidney (HEK) cells (EC50 values of 18 and 2.1 nM, respectively), and it evoked a dose-dependent activation of TRPV4 whole-cell currents at concentrations above 1 nM. In contrast, the TRPV4 activator 4alpha-phorbol 12,13-didecanoate (4alpha-PDD) was 300-fold less potent than GSK1016790A in activating TRPV4 currents. TRPV4 mRNA was detected in urinary bladder smooth muscle (UBSM) and urothelium of TRPV4+/+ mouse bladders. Western blotting and immunohistochemistry demonstrated protein expression in both the UBSM and urothelium that was absent in TRPV4-/- bladders. TRPV4 activation with GSK1016790A contracted TRPV4+/+ mouse bladders in vitro, both in the presence and absence of the urothelium, an effect that was undetected in TRPV4-/- bladders. Consistent with the effects on TRPV4 HEK whole-cell currents, 4alpha-PDD demonstrated a weak ability to contract bladder strips compared with GSK1016790A. In vivo, urodynamics in TRPV4+/+ and TRPV4-/- mice revealed an enhanced bladder capacity in the TRPV4-/- mice. Infusion of GSK1016790A into the bladders of TRPV4+/+ mice induced bladder overactivity with no effect in TRPV4-/- mice. Overall TRPV4 plays an important role in urinary bladder function that includes an ability to contract the bladder as a result of the expression of TRPV4 in the UBSM.
SN - 1521-0103
UR - https://www.unboundmedicine.com/medline/citation/18499743/N___1S__1_{[4___2S__2_{[_24_dichlorophenyl_sulfonyl]amino}_3_hydroxypropanoyl__1_piperazinyl]carbonyl}_3_methylbutyl__1_benzothiophene_2_carboxamide__GSK1016790A__a_novel_and_potent_transient_receptor_potential_vanilloid_4_channel_agonist_induces_urinary_bladder_contraction_and_hyperactivity:_Part_I_
L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=18499743
DB - PRIME
DP - Unbound Medicine
ER -
