title: Role of opioid and metabotropic glutamate 5 receptors in pudendal inhibition of bladder overactivity in cats.
abstract: OBJECTIVE
  We determined the role of opioid and metabotropic glutamate 5 receptors in the pudendal inhibition of bladder overactivity.
  
  
  METHODS
  Cystometrograms were performed in 11 cats under α-chloralose anesthesia by slowly infusing the bladder with saline or 0.25% acetic acid. Pudendal nerve stimulation at intensities of multiple times the threshold to induce observable anal twitching was applied during cystometrogram to inhibit the bladder overactivity induced by acetic acid irritation. Naloxone (0.1, 0.3 and 1 mg/kg intravenously) was administered to block opioid receptors, followed by MTEP (3 and 10 mg/kg intravenously) to block metabotropic glutamate 5 receptors. After each drug dose, pudendal inhibition of bladder overactivity was examined during cystometrogram.
  
  
  RESULTS
  Acetic acid irritated the bladder, induced bladder overactivity and significantly decreased mean ± SE bladder capacity to 23.6% ± 2.7% of saline control capacity. Pudendal nerve stimulation at 1 to 1.5 and 4 × threshold suppressed bladder overactivity and significantly increased mean capacity to 57.5% ± 8.1% (p = 0.0005) and 106% ± 15% (p = 0.0002), respectively, of saline control capacity. Naloxone had no effect on pudendal inhibition but MTEP eliminated the inhibition induced by low intensity stimulation and significantly decreased the inhibition induced by high intensity stimulation (p <0.05). Neither naloxone nor MTEP altered baseline bladder overactivity.
  
  
  CONCLUSIONS
  Opioid receptors are not involved in pudendal inhibition of bladder overactivity but metabotropic glutamate 5 receptors are partially involved. Understanding neurotransmitter mechanisms could improve the efficacy of neuromodulation therapy for overactive bladder and identify molecular targets for developing new drugs for overactive bladder.
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Abhijith D
authors.initials: AD
authors.lastname: Mally
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Matsuta
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.forename: Bing
authors.initials: B
authors.lastname: Shen
authors.forename: Jicheng
authors.initials: J
authors.lastname: Wang
authors.forename: James R
authors.initials: JR
authors.lastname: Roppolo
authors.forename: William C
authors.initials: WC
authors.lastname: de Groat
authors.forename: Changfeng
authors.initials: C
authors.lastname: Tai
mesh_terms: D000818:Animals; D002415:Cats; D005260:Female; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D060525:Pudendal Nerve / Q000503:physiopathology*; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D011957:Receptors, Opioid / Q000502:physiology*; D053201:Urinary Bladder, Overactive / Q000503:physiopathology*
chemical_list: D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D011957:Receptors, Opioid