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Research ArticleGastrointestinal, Hepatic, Pulmonary, and Renal

Modulation of Purinergic Neuromuscular Transmission by Phorbol Dibutyrate is Independent of Protein Kinase C in Murine Urinary Bladder

T. J. Searl and E. M. Silinsky
Journal of Pharmacology and Experimental Therapeutics August 2012, 342 (2) 312-317; DOI: https://doi.org/10.1124/jpet.112.194704
T. J. Searl
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E. M. Silinsky
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Abstract

Parasympathetic control of murine urinary bladder consists of contractile components mediated by both muscarinic and purinergic receptors. Using intracellular recording techniques, the purinergic component of transmission was measured as both evoked excitatory junctional potentials (EJPs) in response to electrical field stimulation and spontaneous events [spontaneous EJPs (sEJPs)]. EJPs, but not sEJPs, were abolished by the application of the Na+ channel blocker tetrodotoxin and the Ca2+ channel blocker Cd2+. Both EJPs and sEJPs were abolished by the application of the P2X1 antagonist 8,8′-[carbonylbis(imino-4,1-phenylenecarbonylimino-4,1-phenylenecarbonylimino)]bis-1,3,5-naphthalenetrisulfonic acid hexasodium salt (NF279). Application of phorbol dibutyrate (PDBu) increased electrically evoked EJP amplitudes with no effect on mean sEJP amplitudes. Similar increases in EJP amplitudes were produced by PDBu in the presence of either the nonselective protein kinase inhibitor staurosporine or the specific protein kinase C (PKC) inhibitor 2-[1-(3-dimethylaminopropyl)indol-3-yl]-3-(indol-3-yl) maleimide (GF109203X). These results suggest that PDBu increases the purinergic component of detrusor transmission through increasing neurogenic ATP release via a PKC-independent mechanism.

Footnotes

  • This work was supported by the National Institutes of Health National Institute on Alcohol Abuse and Alcoholism [Grant AA016513]; the National Institutes of Health National Institute of Neurological Disorders and Stroke [Grant NS12782]; and Northwestern Memorial Hospital.

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

    http://dx.doi.org/10.1124/jpet.112.194704.

  • ABBREVIATIONS:

    ACh
    acetylcholine
    PDBu
    phorbol dibutyrate
    EJP
    excitatory junctional potential
    sEJP
    spontaneous EJP
    TTX
    tetrodotoxin
    PKC
    protein kinase C
    Botox
    botulinum toxin A
    ANOVA
    analysis of variance
    NF279
    8,8′-[carbonylbis(imino-4,1-phenylenecarbonylimino-4,1-phenylenecarbonylimino)]bis-1,3,5-naphthalenetrisulfonic acid hexasodium salt
    GF109203X
    2-[1-(3-dimethylaminopropyl)indol-3-yl]-3-(indol-3-yl) maleimide.

  • Received March 23, 2012.
  • Accepted April 27, 2012.
  • Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 342 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 342, Issue 2
1 Aug 2012
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Research ArticleGastrointestinal, Hepatic, Pulmonary, and Renal

Modulation of Detrusor Neurotransmission by Phorbol Ester

T. J. Searl and E. M. Silinsky
Journal of Pharmacology and Experimental Therapeutics August 1, 2012, 342 (2) 312-317; DOI: https://doi.org/10.1124/jpet.112.194704

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Research ArticleGastrointestinal, Hepatic, Pulmonary, and Renal

Modulation of Detrusor Neurotransmission by Phorbol Ester

T. J. Searl and E. M. Silinsky
Journal of Pharmacology and Experimental Therapeutics August 1, 2012, 342 (2) 312-317; DOI: https://doi.org/10.1124/jpet.112.194704
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