title: A1 Adenosine Receptor-Mediated Inhibition of Parasympathetic Neuromuscular Transmission in Human and Murine Urinary Bladder.
abstract: The potential role of A1 adenosine receptors in modulating neuromuscular transmission in the detrusor muscle of the urinary bladder has been tested in human and murine preparations with the intent to determine the viability of using adenosine receptor agonists as adjuncts to treat overactive bladder. In human detrusor muscle preparations, contractile responses to electrical field stimulation were inhibited by the selective A1 adenosine receptor agonists 2-chloro-N(6)-cyclopentyladenosine, N(6)-cyclopentyladenosine (CPA), and adenosine (rank order of potency: 2-chloro-N(6)-cyclopentyladenosine > CPA > adenosine). Pretreatment with 8-cyclopentyl-3-[3-[[4(fluorosulphonyl)benzoyl]oxy]propyl]-1-propylxanthine, an irreversible A1 antagonist, blocked the effects of CPA, thus confirming the role of A1 receptors in human detrusor preparations. In murine detrusor muscle preparations, contractions evoked by electrical field stimulation were reduced by CPA or adenosine. Amplitudes of the P2X purinoceptor-mediated excitatory junctional potentials (EJPs) recorded with intracellular microelectrodes were reduced in amplitude by CPA and adenosine with no effect on the spontaneous EJP amplitudes, confirming the prejunctional action of these agents. 8-Cyclopentyltheophylline, a selective A1 receptor antagonist, reversed the effects of CPA on EJP amplitudes with no effect of spontaneous EJPs, confirming the role of A1 receptors in mediating these effects.
authors.affiliation: Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, Illinois (T.J.S., E.M.S.); and Division of Urology, Southern Illinois University School of Medicine, Springfield, Illinois (D.I.D., S.R.A., A.M.E.-Z., K.T.M.) tjs026@northwestern.edu.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Searl
authors.affiliation: Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, Illinois (T.J.S., E.M.S.); and Division of Urology, Southern Illinois University School of Medicine, Springfield, Illinois (D.I.D., S.R.A., A.M.E.-Z., K.T.M.).
authors.forename: Danuta I
authors.initials: DI
authors.lastname: Dynda
authors.affiliation: Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, Illinois (T.J.S., E.M.S.); and Division of Urology, Southern Illinois University School of Medicine, Springfield, Illinois (D.I.D., S.R.A., A.M.E.-Z., K.T.M.).
authors.forename: Shaheen R
authors.initials: SR
authors.lastname: Alanee
authors.affiliation: Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, Illinois (T.J.S., E.M.S.); and Division of Urology, Southern Illinois University School of Medicine, Springfield, Illinois (D.I.D., S.R.A., A.M.E.-Z., K.T.M.).
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: El-Zawahry
authors.affiliation: Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, Illinois (T.J.S., E.M.S.); and Division of Urology, Southern Illinois University School of Medicine, Springfield, Illinois (D.I.D., S.R.A., A.M.E.-Z., K.T.M.).
authors.forename: Kevin T
authors.initials: KT
authors.lastname: McVary
authors.affiliation: Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, Illinois (T.J.S., E.M.S.); and Division of Urology, Southern Illinois University School of Medicine, Springfield, Illinois (D.I.D., S.R.A., A.M.E.-Z., K.T.M.).
authors.forename: Eugene M
authors.initials: EM
authors.lastname: Silinsky
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D058907:Adenosine A1 Receptor Agonists / Q000494:pharmacology; D058916:Adenosine A1 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000294:innervation; D010275:Parasympathetic Nervous System / Q000187:drug effects*; D058920:Purinergic P2X Receptor Antagonists / Q000494:pharmacology; D043682:Receptor, Adenosine A1 / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*; D001743:Urinary Bladder / Q000187:drug effects* / Q000294:innervation; D019459:Urothelium / Q000187:drug effects
chemical_list: D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D058920:Purinergic P2X Receptor Antagonists; D043682:Receptor, Adenosine A1; C048599:N(6)-cyclopentyladenosine; D000241:Adenosine