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.
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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