title: Modulation of purinergic neuromuscular transmission by phorbol dibutyrate is independent of protein kinase C in murine urinary bladder.
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 Ca(2+) channel blocker Cd(2+). Both EJPs and sEJPs were abolished by the application of the P2X(1) 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.
authors.affiliation: Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, IL 60611, USA. tjs026@northwestern.edu
authors.forename: T J
authors.initials: TJ
authors.lastname: Searl
authors.forename: E M
authors.initials: EM
authors.lastname: Silinsky
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D004558:Electric Stimulation / Q000379:methods; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D058905:Purinergic Agents / Q000494:pharmacology; D058920:Purinergic P2X Receptor Antagonists / Q000494:pharmacology; D011983:Receptors, Purinergic / Q000378:metabolism*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000378:metabolism; D013498:Suramin / Q000031:analogs & derivatives / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects; D001743:Urinary Bladder / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; C114657:NF 279; D018377:Neurotransmitter Agents; D010703:Phorbol Esters; D047428:Protein Kinase Inhibitors; D058905:Purinergic Agents; D058920:Purinergic P2X Receptor Antagonists; D011983:Receptors, Purinergic; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D015240:Phorbol 12,13-Dibutyrate; D013498:Suramin; D000255:Adenosine Triphosphate; D011493:Protein Kinase C