Interactions between NMDA and AMPA/kainate receptors in the control of micturition in the rat.
In unanesthetized decerebrate rats, GYKI 52466 (1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride), an AMPA/kainate receptor antagonist, and MK-801 (dizocilpine), an NMDA receptor antagonist, acted synergistically to depress the micturition reflex. MK-801 (1 mg/kg i.v.) and GYKI 52466 (4 mg/kg i.v.) administered separately had no or only a small depressant effect on reflex bladder contractions but markedly depressed external urethral sphincter activity. However, in MK-801-treated rats, GYKI 52466 decreased the amplitude, frequency and duration of reflex bladder contractions. These results suggest that both AMPA/kainate and NMDA glutamate receptors are important in the micturition reflex pathway and that these receptors may be activated in parallel at some site in the pathway so that excitatory transmission via only one receptor type is sufficient to mediate reflex activation of the bladder.
Yoshiyama
M
M
Department of Pharmacology, University of Pittsburgh, PA 15261, USA.
Roppolo
J R
JR
De Groat
W C
WC
D000818:Animals; D014151:Anti-Anxiety Agents; D001569:Benzodiazepines / Q000494:pharmacology*; D001794:Blood Pressure; D003655:Decerebrate State; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004338:Drug Combinations; D004357:Drug Synergism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D009125:Muscle Relaxants, Central / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D012018:Reflex / Q000187:drug effects*; D001743:Urinary Bladder / Q000187:drug effects*; D014554:Urination / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D004338:Drug Combinations; D018691:Excitatory Amino Acid Antagonists; D009125:Muscle Relaxants, Central; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D014665:Vasodilator Agents; C061950:GYKI 52466; D001569:Benzodiazepines; D009599:Nitroprusside; D016291:Dizocilpine Maleate