title: Supraspinal and spinal alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid and N-methyl-D-aspartate glutamatergic control of the micturition reflex in the urethane-anesthetized rat.
abstract: Effects of i.c.v. and i.t. administration of (3SR,4aRS,6RS,8aRS)-6-[2-(1H-tetrazol-5-yl)ethyl]decahydroisoquinoline-3-carboxylic acid (LY215490), a competitive alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonist and MK-801, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist on the micturition reflex were evaluated in urethane-anesthetized rats, to determine if glutamatergic mechanisms in brain as well as spinal cord are important for the control of micturition. I.c.v. or i.t. injection of LY215490 in low doses (0.01-0.03 microg) did not change rhythmic bladder or external urethral sphincter (EUS) electromyogram (EMG) activity during continuous cystometrograms (CMGs; 0.21 ml/min), whereas higher doses (0.1-1 microg) markedly suppressed these responses. During single CMGs (0.04 ml/min), 0.1-1 microg i.c.v. or 0.1-10 microg i.t. doses increased volume threshold and pressure threshold for inducing micturition, and decreased bladder contraction amplitude and voiding efficiency. MK-801 in low doses (0.6 microg i.c.v. or 0.6-1.8 microg for i.t.) did not change bladder contraction amplitude or EUS EMG activity during continuous CMGs, whereas higher doses 6-60 microg markedly suppressed these responses. During single CMGs, MK-801 (6-60 microg i.c.v. or 60 microg i.t.) increased volume threshold and pressure threshold, and decreased voiding efficiency and bladder contraction amplitude. Pretreatment i.c.v. with MK-801 in a dose 1.8 microg which alone had little effect on bladder contraction amplitude and EUS EMG activity, markedly enhanced depressant effects of LY215490 (0.03 microg i.c.v.) on these responses. Administration of same doses of drugs by i.t. route did not elicit a similar synergistic interaction. These data indicate that in urethane-anesthetized rats glutamatergic mechanisms in brain and spinal cord are essential for controlling micturition and that interactions between AMPA and NMDA glutamatergic transmission are important at supraspinal but not spinal sites.
authors.affiliation: Department of Pharmacology, University of Pittsburgh School of Medicine, PA 15261, USA. pxn15164@nifty.ne.jp
authors.forename: M
authors.initials: M
authors.lastname: Yoshiyama
authors.forename: W C
authors.initials: WC
authors.lastname: de Groat
mesh_terms: D000758:Anesthesia; D018686:Anesthetics, Intravenous / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology; D016291:Dizocilpine Maleate / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004576:Electromyography; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D007546:Isoquinolines / Q000008:administration & dosage*; D016202:N-Methylaspartate / Q000378:metabolism*; D009434:Neural Pathways / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology; D013777:Tetrazoles / Q000008:administration & dosage*; D014520:Urethane / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects / Q000294:innervation; D014554:Urination / Q000502:physiology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism*
chemical_list: D018686:Anesthetics, Intravenous; D018691:Excitatory Amino Acid Antagonists; D007546:Isoquinolines; D013777:Tetrazoles; D014520:Urethane; D018698:Glutamic Acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; C082309:tezampanel; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid