Effects of glutamate receptor antagonists on lower urinary tract function in conscious unanesthetized rats.
OBJECTIVE
To study the effects of the intrathecal administered glutamate receptor antagonists on the bladder and urethral activities during isovolumetric bladder contraction in conscious normal and chronic spinal rats.


METHODS
Twenty-eight female Wistar rats with and without previous spinal cord transection were used. Before and after intrathecal administration of glutamate receptor antagonist, urodynamic parameters under isovolmetric condition of the bladder were analyzed.


RESULTS
In normal rats, MK-801 (noncompetitive N-methyl-D-aspartate [NMDA] receptor antagonist) and LY 293558 (competitive AMPA receptor antagonist) produced a decrease in bladder contraction pressure and urethral activity with dose dependent manner. In chronic spinal rats, detrusor-sphincter dyssynergia (DSD) was developed before drug administration. MK-801 and LY 293558 partially inhibited bladder contraction pressure, and markedly depressed urethral contraction concomitant with bladder contraction. LY 293558 produced urethral relaxation concomitant with bladder contraction.


CONCLUSIONS
In both normal rats and chronic spinal rats, two subtypes of glutamate receptors (NMDA and AMPA receptors) in the spinal cord were involved in the control of bladder and urethral activities. The AMPA receptor in the spinal cord seems to take an important role in the development of DSD.
Nishizawa
O
O
Department of Urology, Shinshu University School of Medicine, Matsumoto City, Japan.
Igawa
Y
Y
Satoh
T
T
Yamashiro
S
S
Sugaya
K
K
D000818:Animals; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D007278:Injections, Spinal; D007546:Isoquinolines / Q000008:administration & dosage / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D017470:Receptors, Glutamate / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology*; D014563:Urodynamics / Q000187:drug effects / Q000502:physiology
D018691:Excitatory Amino Acid Antagonists; D007546:Isoquinolines; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D013777:Tetrazoles; D016291:Dizocilpine Maleate; C082309:tezampanel