title: Contribution of opioid and metabotropic glutamate receptor mechanisms to inhibition of bladder overactivity by tibial nerve stimulation.
abstract: The contribution of metabotropic glutamate receptors (mGluR) and opioid receptors to inhibition of bladder overactivity by tibial nerve stimulation (TNS) was investigated in cats under α-chloralose anesthesia using LY341495 (a group II mGluR antagonist) and naloxone (an opioid receptor antagonist). Slow infusion cystometry was used to measure the volume threshold (i.e., bladder capacity) for inducing a large bladder contraction. After measuring the bladder capacity during saline infusion, 0.25% acetic acid (AA) was infused to irritate the bladder, activate the nociceptive C-fiber bladder afferents, and induce bladder overactivity. AA significantly (P < 0.0001) reduced bladder capacity to 26.6 ± 4.7% of saline control capacity. TNS (5 Hz, 0.2 ms) at 2 and 4 times the threshold (T) intensity for inducing an observable toe movement significantly increased bladder capacity to 62.2 ± 8.3% at 2T (P < 0.01) and 80.8 ± 9.2% at 4T (P = 0.0001) of saline control capacity. LY341495 (0.1-5 mg/kg iv) did not change bladder overactivity, but completely suppressed the inhibition induced by TNS at a low stimulus intensity (2T) and partially suppressed the inhibition at high intensity (4T). Following administration of LY341495, naloxone (0.01 mg/kg iv) completely eliminated the high-intensity TNS-induced inhibition. However, without LY341495 treatment a 10 times higher dose (0.1 mg/kg) of naloxone was required to completely block TNS inhibition. These results indicate that interactions between group II mGluR and opioid receptor mechanisms contribute to TNS inhibition of AA-induced bladder overactivity. Understanding neurotransmitter mechanisms underlying TNS inhibition of bladder overactivity is important for the development of new treatments for bladder disorders.
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, PA 15213, USA.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Matsuta
authors.forename: Abhijith D
authors.initials: AD
authors.lastname: Mally
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: D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D002415:Cats; D004599:Electric Stimulation Therapy / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D011957:Receptors, Opioid / Q000378:metabolism*; D013979:Tibial Nerve / Q000502:physiology*; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism*; D053201:Urinary Bladder, Overactive / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D014966:Xanthenes / Q000494:pharmacology
chemical_list: D000596:Amino Acids; D018691:Excitatory Amino Acid Antagonists; C114624:LY 341495; D009292:Narcotic Antagonists; D018094:Receptors, Metabotropic Glutamate; D011957:Receptors, Opioid; D014966:Xanthenes; D009270:Naloxone
keywords: bladder; cat; neuromodulation; neurotransmitter