title: Neurotransmitter Mechanisms Underlying Sacral Neuromodulation of Bladder Overactivity in Cats.
abstract: OBJECTIVE
  To determine the role of opioid, β-adrenergic, and metabotropic glutamate 5 receptors in sacral neuromodulation of bladder overactivity.
  
  
  METHODS
  In α-chloralose anesthetized cats, intravesical infusion of 0.5% acetic acid (AA) irritated the bladder and induced bladder overactivity. Electric stimulation (5 Hz, 0.2 ms, 0.16-0.7V) of S1 or S2 sacral dorsal roots inhibited the bladder overactivity. Naloxone, propranolol, or MTEP were given intravenously (i.v.) to determine different neurotransmitter mechanisms.
  
  
  RESULTS
  AA significantly (p < 0.05) reduced bladder capacity to 7.7 ± 3.3 mL from 12.0 ± 5.0 mL measured during saline infusion. S1 or S2 stimulation at motor threshold intensity significantly (p < 0.05) increased bladder capacity to 179.4 ± 20.0% or 219.1 ± 23.0% of AA control, respectively. Naloxone (1 mg/kg) significantly (p < 0.001) reduced the control capacity to 38.3 ± 7.3% and the bladder capacity measured during S1 stimulation to 106.2 ± 20.8% of AA control, but did not significantly change the bladder capacity measured during S2 stimulation. Propranolol (3 mg/kg) significantly (p < 0.01) reduced bladder capacity from 251.8 ± 32.2% to 210.9 ± 33.3% during S2 stimulation, but had no effect during S1 stimulation. A similar propranolol effect also was observed in naloxone-pretreated cats. In propranolol-pretreated cats during S1 or S2 stimulation, MTEP (3 mg/kg) significantly (p < 0.05) reduced bladder capacity and naloxone (1 mg/kg) following MTEP treatment further reduced bladder capacity. However, a significant inhibition could still be induced by S1 or S2 stimulation after all three drugs were administered.
  
  
  CONCLUSIONS
  Neurotransmitter mechanisms in addition to those activating opioid, β-adrenergic, and metabotropic glutamate 5 receptors also are involved in sacral neuromodulation.
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Jathin
authors.initials: J
authors.lastname: Bandari
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Utsav
authors.initials: U
authors.lastname: Bansal
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, PA, USA.|Department of Urology, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Zhaocun
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: Shen
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Jicheng
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Lamm
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Chang
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Roppolo
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: William C
authors.initials: WC
authors.lastname: de Groat
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, PA, USA.|Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Changfeng
authors.initials: C
authors.lastname: Tai
mesh_terms: D019342:Acetic Acid / Q000633:toxicity; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000704:Analysis of Variance; D000818:Animals; D002415:Cats; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use; D005260:Female; D007202:Indicators and Reagents / Q000633:toxicity; D008297:Male; D009270:Naloxone / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000627:therapeutic use; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011433:Propranolol / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D012447:Sacrum; D062187:Spinal Cord Stimulation / Q000379:methods*; D013126:Spinal Nerve Roots / Q000502:physiology*; D013844:Thiazoles / Q000627:therapeutic use; D053201:Urinary Bladder, Overactive / Q000139:chemically induced / Q000378:metabolism* / Q000628:therapy*
chemical_list: C472365:3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine; D000319:Adrenergic beta-Antagonists; D018691:Excitatory Amino Acid Antagonists; D007202:Indicators and Reagents; D009292:Narcotic Antagonists; D018377:Neurotransmitter Agents; D011725:Pyridines; D013844:Thiazoles; D009270:Naloxone; D011433:Propranolol; D019342:Acetic Acid
keywords: Bladder; cat; neuromodulation; neurotransmitter