Alteration by urethane of glutamatergic control of micturition.
The i.v. administration of MK-801 (0.001-3 mg/kg), a non-competitive NMDA receptor antagonist, did not alter reflex bladder activity in unanesthetized decerebrate rat recorded during fast infusion (0.21 ml/min) cystometry or under isovolumetric conditions, but did depress reflex bladder contractions in doses between 0.1 and 3 mg/kg i.v. in the urethane-anesthetized (1.2 g/kg s.c.) intact rat during fast infusion cystometry. The ED50 and the dose to produce maximal inhibition in urethane-anesthetized intact rats were 0.25 mg/kg and 3 mg/kg i.v., respectively. During slow infusion (0.04 ml/min) cystometry, in unanesthetized decerebrate rats, MK-801 (0.1-1 mg/kg i.v. or 6-60 micrograms i.t.) decreased by 12-44% the micturition volume threshold (VT) but did not change the amplitude and duration of the bladder contractions. The administration of a larger i.t. dose (60 micrograms) of MK-801 produced no further decrease in VT but decreased the amplitude of bladder contractions by 24%. External urethral sphincter electromyogram activity was reduced or abolished by MK-801 (0.01-3 mg/kg i.v.) in both unanesthetized decerebrate and urethane-anesthetized intact rats with ED50 of 0.12 mg/kg and 0.05 mg/kg, respectively. These results indicate that NMDA receptors play an important role in both facilitatory and inhibitory central neural control of voiding function and that there is a significant interaction between urethane anesthesia and NMDA glutamatergic transmission. Thus, even though urethane anesthesia has been useful for studying the physiological characteristics of the micturition reflex, it seems inappropriate for analyzing the normal transmitter role of glutamic acid in reflex voiding.
Yoshiyama
M
M
Department of Pharmacology, School of Medicine, University of Pittsburgh, PA 15261.
Roppolo
J R
JR
De Groat
W C
WC
D000704:Analysis of Variance; D000818:Animals; D003558:Cystoscopy; D003655:Decerebrate State; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004576:Electromyography; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D007263:Infusions, Parenteral; D007275:Injections, Intravenous; D007278:Injections, Spinal; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000502:physiology; D014520:Urethane / Q000008:administration & dosage / Q000494:pharmacology*; D001743:Urinary Bladder / Q000187:drug effects*; D014554:Urination / Q000187:drug effects*
D016194:Receptors, N-Methyl-D-Aspartate; D014520:Urethane; D018698:Glutamic Acid; D016291:Dizocilpine Maleate