title: Influence of urothelial or suburothelial cholinergic receptors on bladder reflexes in chronic spinal cord injured cats.
abstract: The effects of intravesical administration of a muscarinic receptor agonist (oxotremorine-M, OXO-M) and antagonist (atropine methyl nitrate, AMN) and of a nicotinic receptor agonist (nicotine) and antagonist (hexamethonium, C6) on reflex bladder activity were investigated in conscious female chronic spinal cord injured (SCI) cats using cystometry. OXO-M (50μM) decreased bladder capacity (BC) for triggering micturition contractions, increased maximal micturition pressure (MMP), increased frequency and area under the curve of pre-micturition contractions (PMC-AUC). Nicotine (250μM) decreased BC, increased MMP, but did not alter PMC-AUC. The effects of OXO-M on BC and PMC-AUC were suppressed by intravesical administration of AMN (50-100μM), and the effects of nicotine were blocked by hexamethonium (1mM). Antagonists infused intravesically alone did not alter reflex bladder activity. However, AMN (0.2mg/kg, subcutaneously) decreased PMC-AUC. 8-OH-DPAT (0.5mg/kg, s.c.), a 5-HT1Areceptor agonist, suppressed the OXO-M-induced decrease in BC but not the enhancement of PMC-AUC. These results indicate that activation of cholinergic receptors located near the lumenal surface of the bladder modulates two types of reflex bladder activity (i.e., micturition and pre-micturition contractions). The effects may be mediated by activation of receptors on suburothelial afferent nerves or receptors on urothelial cells which release transmitters that can in turn alter afferent excitability. The selective action of nicotine on BC, while OXO-M affects both BC and PMC-AUC, suggests that micturition reflexes and PMCs are activated by different populations of afferent nerves. The selective suppression of the OXO-M effect on BC by 8-OH-DPAT without altering the effect on PMCs supports this hypothesis. The failure of intravesical administration of either AMN or hexamethonium alone to alter bladder activity indicates that cholinergic receptors located near the lumenal surface do not tonically regulate bladder reflex mechanisms in the SCI cat.
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Ungerer
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
authors.forename: Kyoungeun A
authors.initials: KA
authors.lastname: Kim
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Daugherty
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Roppolo
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA; Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
authors.forename: Changfeng
authors.initials: C
authors.lastname: Tai
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA. Electronic address: wcd2@pitt.edu.
authors.forename: William C
authors.initials: WC
authors.lastname: de Groat
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D002415:Cats; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D018721:Muscarinic Agonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D010095:Oxotremorine / Q000494:pharmacology; D011950:Receptors, Cholinergic / Q000378:metabolism*; D012018:Reflex / Q000187:drug effects / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013119:Spinal Cord Injuries / Q000473:pathology* / Q000503:physiopathology*; D001743:Urinary Bladder / Q000187:drug effects / Q000503:physiopathology*; D014554:Urination / Q000187:drug effects / Q000502:physiology*
chemical_list: D018721:Muscarinic Agonists; D018722:Nicotinic Agonists; D011950:Receptors, Cholinergic; D017366:Serotonin Receptor Agonists; D010095:Oxotremorine; D009538:Nicotine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin
keywords: Afferent nerve; Bladder reflex; Cholinergic receptor; Micturition; Nicotine; Spinal injury; Urothelium