RT Journal Article
SR Electronic
T1 Contribution of GABA<sub>A</sub>, Glycine, and Opioid Receptors to Sacral Neuromodulation of Bladder Overactivity in Cats
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 436
OP 441
DO 10.1124/jpet.116.235846
VO 359
IS 3
A1 Jiang, Xuewen
A1 Fuller, Thomas W.
A1 Bandari, Jathin
A1 Bansal, Utsav
A1 Zhang, Zhaocun
A1 Shen, Bing
A1 Wang, Jicheng
A1 Roppolo, James R.
A1 de Groat, William C.
A1 Tai, Changfeng
YR 2016
UL http://jpet.aspetjournals.org/content/359/3/436.abstract
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 &lt; 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 &lt; 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 &lt; 0.05) poststimulation inhibition that persisted after termination of stimulation. Naloxone, an opioid receptor antagonist (0.3 mg, i.t.), significantly (P &lt; 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 &lt; 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 &lt; 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.