title: Contribution of GABAA, Glycine, and Opioid Receptors to Sacral Neuromodulation of Bladder Overactivity in Cats.
abstract: In α-chloralose-anesthetized cats, we examined the role of GABAA, glycine, and opioid receptors in sacral neuromodulation-induced inhibition of bladder overactivity elicited by intravesical infusion of 0.5% acetic acid (AA). AA irritation significantly (P < 0.01) reduced bladder capacity to 59.5 ± 4.8% of saline control. S1 or S2 dorsal root stimulation at threshold intensity for inducing reflex twitching of the anal sphincter or toe significantly (P < 0.01) increased bladder capacity to 105.3 ± 9.0% and 134.8 ± 8.9% of saline control, respectively. Picrotoxin, a GABAAreceptor antagonist administered i.v., blocked S1 inhibition at 0.3 mg/kg and blocked S2 inhibition at 1.0 mg/kg. Picrotoxin (0.4 mg, i.t.) did not alter the inhibition induced during S1 or S2 stimulation, but unmasked a significant (P < 0.05) poststimulation inhibition that persisted after termination of stimulation. Naloxone, an opioid receptor antagonist (0.3 mg, i.t.), significantly (P < 0.05) reduced prestimulation bladder capacity and removed the poststimulation inhibition. Strychnine, a glycine receptor antagonist (0.03-0.3 mg/kg, i.v.), significantly (P < 0.05) increased prestimulation bladder capacity but did not reduce sacral S1 or S2 inhibition. After strychnine (0.3 mg/kg, i.v.), picrotoxin (0.3 mg/kg, i.v.) further (P < 0.05) increased prestimulation bladder capacity and completely blocked both S1 and S2 inhibition. These results indicate that supraspinal GABAAreceptors play an important role in sacral neuromodulation of bladder overactivity, whereas glycine receptors only play a minor role to facilitate the GABAAinhibitory mechanism. The poststimulation inhibition unmasked by blocking spinal GABAAreceptors was mediated by an opioid mechanism.
authors.affiliation: Department of Urology, Qilu Hospital, Shandong University, Jinan, P.R. China (X.J., Z.Z.); Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania (X.J., T.W.F., J.B., U.B., Z.Z., B.S., J.W., C.T.); and Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania (J.R.R., W.C.d.G., C.T.).
authors.forename: Xuewen
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Urology, Qilu Hospital, Shandong University, Jinan, P.R. China (X.J., Z.Z.); Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania (X.J., T.W.F., J.B., U.B., Z.Z., B.S., J.W., C.T.); and Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania (J.R.R., W.C.d.G., C.T.).
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Fuller
authors.affiliation: Department of Urology, Qilu Hospital, Shandong University, Jinan, P.R. China (X.J., Z.Z.); Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania (X.J., T.W.F., J.B., U.B., Z.Z., B.S., J.W., C.T.); and Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania (J.R.R., W.C.d.G., C.T.).
authors.forename: Jathin
authors.initials: J
authors.lastname: Bandari
authors.affiliation: Department of Urology, Qilu Hospital, Shandong University, Jinan, P.R. China (X.J., Z.Z.); Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania (X.J., T.W.F., J.B., U.B., Z.Z., B.S., J.W., C.T.); and Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania (J.R.R., W.C.d.G., C.T.).
authors.forename: Utsav
authors.initials: U
authors.lastname: Bansal
authors.affiliation: Department of Urology, Qilu Hospital, Shandong University, Jinan, P.R. China (X.J., Z.Z.); Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania (X.J., T.W.F., J.B., U.B., Z.Z., B.S., J.W., C.T.); and Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania (J.R.R., W.C.d.G., C.T.).
authors.forename: Zhaocun
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Urology, Qilu Hospital, Shandong University, Jinan, P.R. China (X.J., Z.Z.); Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania (X.J., T.W.F., J.B., U.B., Z.Z., B.S., J.W., C.T.); and Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania (J.R.R., W.C.d.G., C.T.).
authors.forename: Bing
authors.initials: B
authors.lastname: Shen
authors.affiliation: Department of Urology, Qilu Hospital, Shandong University, Jinan, P.R. China (X.J., Z.Z.); Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania (X.J., T.W.F., J.B., U.B., Z.Z., B.S., J.W., C.T.); and Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania (J.R.R., W.C.d.G., C.T.).
authors.forename: Jicheng
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Urology, Qilu Hospital, Shandong University, Jinan, P.R. China (X.J., Z.Z.); Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania (X.J., T.W.F., J.B., U.B., Z.Z., B.S., J.W., C.T.); and Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania (J.R.R., W.C.d.G., C.T.).
authors.forename: James R
authors.initials: JR
authors.lastname: Roppolo
authors.affiliation: Department of Urology, Qilu Hospital, Shandong University, Jinan, P.R. China (X.J., Z.Z.); Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania (X.J., T.W.F., J.B., U.B., Z.Z., B.S., J.W., C.T.); and Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania (J.R.R., W.C.d.G., C.T.).
authors.forename: William C
authors.initials: WC
authors.lastname: de Groat
authors.affiliation: Department of Urology, Qilu Hospital, Shandong University, Jinan, P.R. China (X.J., Z.Z.); Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania (X.J., T.W.F., J.B., U.B., Z.Z., B.S., J.W., C.T.); and Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania (J.R.R., W.C.d.G., C.T.) cftai@pitt.edu.
authors.forename: Changfeng
authors.initials: C
authors.lastname: Tai
mesh_terms: D000818:Animals; D002415:Cats; D004558:Electric Stimulation; D005260:Female; D008297:Male; D009270:Naloxone / Q000494:pharmacology / Q000627:therapeutic use; D010852:Picrotoxin / Q000494:pharmacology / Q000627:therapeutic use; D011963:Receptors, GABA-A / Q000378:metabolism*; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011957:Receptors, Opioid / Q000378:metabolism*; D013127:Spinal Nerves / Q000503:physiopathology; D013331:Strychnine / Q000494:pharmacology / Q000627:therapeutic use; D053201:Urinary Bladder, Overactive / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D009270:Naloxone; D010852:Picrotoxin; D011963:Receptors, GABA-A; D018009:Receptors, Glycine; D011957:Receptors, Opioid; D013331:Strychnine