PT  - JOURNAL ARTICLE
AU  - Jiang, Xuewen
AU  - Fuller, Thomas W.
AU  - Bandari, Jathin
AU  - Bansal, Utsav
AU  - Zhang, Zhaocun
AU  - Shen, Bing
AU  - Wang, Jicheng
AU  - Roppolo, James R.
AU  - de Groat, William C.
AU  - Tai, Changfeng
TI  - Contribution of GABA<sub>A</sub>, Glycine, and Opioid Receptors to Sacral Neuromodulation of Bladder Overactivity in Cats
AID  - 10.1124/jpet.116.235846
DP  - 2016 Dec 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 436--441
VI  - 359
IP  - 3
4099  - http://jpet.aspetjournals.org/content/359/3/436.short
4100  - http://jpet.aspetjournals.org/content/359/3/436.full
SO  - J Pharmacol Exp Ther2016 Dec 01; 359
AB  - 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 GABAA receptor 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 GABAA receptors play an important role in sacral neuromodulation of bladder overactivity, whereas glycine receptors only play a minor role to facilitate the GABAA inhibitory mechanism. The poststimulation inhibition unmasked by blocking spinal GABAA receptors was mediated by an opioid mechanism.