Suppression of detrusor-sphincter dysynergia by GABA-receptor activation in the lumbosacral spinal cord in spinal cord-injured rats.
We investigated the effects of intrathecal application of GABAA- or GABAB-receptor agonists on detrusor-sphincter dyssynergia (DSD) in spinal cord transection (SCT) rats. Adult female Sprague-Dawley rats were used. At 4 wk after Th9-10 SCT, simultaneous recordings of intravesical pressure and urethral pressure were performed under an awake condition to examine the effect of intrathecal application of GABAA and GABAB agonists (muscimol and baclofen, respectively) or GABAA and GABAB antagonists (bicuculline and saclofen, respectively) at the level of L6-S1 spinal cord. In spinal-intact rats, the effects of bicuculline and saclofen on bladder and urethral activity were also examined. During urethral pressure measurements, DSD characterized by urethral pressure increases during isovolumetric bladder contractions were observed in 95% of SCT rats. However, after intrathecal application of muscimol or baclofen, urethral pressure showed urethral relaxation during isovolumetric bladder contractions. The effective dose to induce inhibition of urethral activity was lower compared with the dose that inhibited bladder contractions. The effect of muscimol and baclofen was antagonized by intrathecal bicuculline and saclofen, respectively. In spinal-intact rats, intrathecal application of bicuculline induced DSD-like changes. These results indicate that GABAA- and GABAB-receptor activation in the spinal cord exerts the inhibitory effects on DSD after SCT. Decreased activation of GABAA receptors due to hypofunction of GABAergic mechanisms in the spinal cord might be responsible, at least in part, for the development of DSD after SCT.
Miyazato
Minoru
M
Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Sasatomi
Kurumi
K
Hiragata
Shiro
S
Sugaya
Kimio
K
Chancellor
Michael B
MB
de Groat
William C
WC
Yoshimura
Naoki
N
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D008161:Lumbosacral Region; D009118:Muscimol / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology; D013119:Spinal Cord Injuries / Q000378:metabolism*; D014521:Urethra / Q000187:drug effects / Q000502:physiology; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology*
D018755:GABA Agonists; D018756:GABA Antagonists; D018079:Receptors, GABA; D009118:Muscimol; D001418:Baclofen