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Vol. 280, Issue 2, 894-904, 1997
-Amino-3-Hydroxy-5-Methylisoxazole-4-Propionic Acid (AMPA) Receptor
Antagonist, on the Micturition Reflex in the Rat1
Department of Pharmacology, School of Medicine, University of
Pittsburgh, Pittsburgh, Pennsylvania
The effects of glutamate receptor antagonists on urinary bladder and
external urethral sphincter- (EUS) electromyogram (EMG) activity were
evaluated in unanesthetized decerebrate rats. In normal rats, LY215490,
an 
-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)
receptor antagonist, in small i.v. doses (1-3 mg/kg) decreased bladder
contraction amplitude (BC-Amp) by 29% and EUS-EMG by 41%; whereas a
large dose (10 mg/kg) completely abolished bladder and EUS-EMG
activity. LY215490 injected intrathecally in small doses (0.01-0.1
µg) decreased BC-Amp by 20% and EUS-EMG by 62%; whereas large doses
(1-10 µg) completely abolished bladder and EUS-EMG activity.
LY215490 (0.1 µg i.t.) increased bladder capacity by 28% and
decreased voiding efficiency by 44%. Combined i.t. administration of
small doses of LY215490 (0.1 µg) and MK-801 (1 µg), an
N-methyl-D-aspartate (NMDA) receptor antagonist,
which individually had little effect on BC-Amp, markedly suppressed bladder activity. In chronic spinal rats, LY215490 (10 mg/kg i.v.) abolished EUS-EMG activity and decreased BC-Amp by 41%. Intrathecal injections of LY215490 were also less effective in chronic spinal rats;
a 10-µg dose producing only a partial block (53%) of BC-Amp, but
complete block of EUS-EMG. In chronic spinal rats, MK-801 (1 mg/kg
i.v.) abolished EUS-EMG activity and decreased BC-Amp by 36%.
Pretreatment with MK-801 (1 mg/kg i.v.) did not enhance the effect of
LY215490 on bladder activity in chronic spinal rats. These data suggest
that AMPA glutamate receptors have a major role in the excitatory
pathways controlling bladder and EUS activity in spinal cord intact
rats. However, in chronic spinal rats, AMPA and NMDA receptors are
essential for EUS reflexes, but are responsible for only a part of
reflex bladder activity.
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