Effects of a selective metabotropic glutamate receptor agonist on the micturition reflex pathway in urethane-anesthetized rats.
OBJECTIVE
To determine a possible role of metabotropic glutamate receptors in the spinobulbospinal micturition reflex pathway in the rat.


METHODS
A selective metabotropic glutamate receptor agonist, trans-(+/-)-1-amino1,3-cyclopentanedicarboxylic acid (trans-ACPD) was administered to the lumbosacral spinal cord via an intrathecal catheter in urethane anesthetized rats. Amplitude of reflex bladder contractions evoked by bladder distension under isovolumetric condition as well as amplitude of bladder contractions elicited by electrical stimulation of the pontine micturition center (PMC) were examined before and after administration of trans-ACPD. The effect of trans-ACPD on the urethral activity during isovolumetric bladder contractions was also examined by monitoring urethral perfusion pressure and electromyography of the external urethral sphincter (EUS-EMG).


RESULTS
Trans-ACPD (3-10 microg) completely inhibited reflex bladder contractions evoked by bladder distension and the duration of inhibition was dose dependent (3 microg: 11.4 +/- 2.8 min, 5 microg: 13.2 +/- 1.3 min, 10 microg: 36.2 +/- 2.4 min). The mean amplitude of bladder contractions evoked by electrical stimulation of the PMC was reduced to 12.6 +/- 2.3% of control by 10 microg of trans-ACPD. In addition, bursting activity of EUS-EMG and corresponding high frequency oscillations of urethral pressure during isovolumetric bladder contractions were completely abolished by 10 microg of trans-ACPD.


CONCLUSIONS
These results indicate that intrathecal administration of a selective metabotropic glutamate receptor agonist to the lumbosacral spinal cord has an inhibitory effect on the spinobulbospinal micturition reflex pathway in urethane-anesthetized rats. This pharmacological action is attributed at least to the inhibitory effect on the descending pathway from the PMC to the lumbosacral spinal cord.
Tanaka
Hiroshi
H
The Department of Urology, Hokkaido University Graduate School of Medicine, Sapporo, Japan. h-tanaka@med.hokudai.ac.jp
Kakizaki
Hidehiro
H
Shibata
Takashi
T
Ameda
Kaname
K
Koyanagi
Tomohiko
T
D000771:Anesthesia, Intravenous; D018686:Anesthetics, Intravenous; D000818:Animals; D003515:Cycloleucine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D004558:Electric Stimulation; D004576:Electromyography; D007275:Injections, Intravenous; D007278:Injections, Spinal; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*; D012018:Reflex / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*; D014520:Urethane; D001743:Urinary Bladder / Q000503:physiopathology; D014554:Urination / Q000187:drug effects*
D018686:Anesthetics, Intravenous; D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D014520:Urethane