RT Journal Article
SR Electronic
T1 Effects of LY215490, a Competitive α-Amino-3-Hydroxy-5-Methylisoxazole-4-Propionic Acid (AMPA) Receptor Antagonist, on the Micturition Reflex in the Rat
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 894
OP 904
VO 280
IS 2
A1 Yoshiyama, Mitsuharu
A1 Roppolo, James R.
A1 Groat, William C. de
YR 1997
UL http://jpet.aspetjournals.org/content/280/2/894.abstract
AB 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 α-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), anN-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. The American Society for Pharmacology and Experimental Therapeutics