title: Role of spinal glutamatergic transmission in the ascending limb of the micturition reflex pathway in the rat.
abstract: This study was undertaken to evaluate the role of glutamate receptors at spinal synapses on the ascending limb of the micturition reflex. In urethane-anesthetized female rats, a tungsten electrode was inserted stereotaxically into the dorsal part of the rostral pons to record field potentials which were evoked by electrical stimulation of the pelvic nerve (PLN) (1-15 V, 0.05 ms pulse duration at 100-300 Hz, 5-30 ms train duration). The effects of glutamate receptor antagonists administered intrathecally (i.t.) on the PLN-evoked field potentials in the dorsal part of the rostral brainstem were examined. PLN stimulation evoked short latency (10-22 ms) negative field potentials (85 +/- 4 microV) in a limited area of the dorsal part of the rostral pons (bregma -9.0 to -8.4, L 0.5 to 1. 5, H 4.2 to 5.4). The i.t. administration of LY215490 (0.1-30 microg), a competitive alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonist, reduced the amplitude of the evoked potentials in a dose-dependent manner; 84 +/- 6%, 59 +/- 11% (P < .001), 31 +/- 10% (P < .001), 17 +/- 9% (P < .001) of control after 0.1, 1, 10, 30 microg of LY215490, respectively. The i.t. administration of MK-801 (1-100 microg), a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, also reduced the amplitude of the evoked potentials in a dose-dependent manner; 93 +/- 21%, 76 +/- 14%, 52 +/- 9% (P < .001), 39 +/- 9% (P < .001) of control after 1, 10, 30, 100 microg of MK-801, respectively. Combined administration of LY215490 (0.1 microg) and MK-801 (1 microg), in doses which individually did not elicit a significant effect, markedly reduced the amplitude of the evoked potentials (27 +/- 9% of control, P = . 0002). These results suggest that AMPA and NMDA glutamatergic synaptic mechanisms play a key role in the spinal processing of afferent input from the bladder and that these mechanisms function synergistically in the ascending limb of the spinobulbospinal micturition reflex pathway.
authors.affiliation: Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
authors.forename: H
authors.initials: H
authors.lastname: Kakizaki
authors.forename: M
authors.initials: M
authors.lastname: Yoshiyama
authors.forename: J R
authors.initials: JR
authors.lastname: Roppolo
authors.forename: A M
authors.initials: AM
authors.lastname: Booth
authors.forename: W C
authors.initials: WC
authors.lastname: De Groat
mesh_terms: D000344:Afferent Pathways / Q000187:drug effects*; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004338:Drug Combinations; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005121:Extremities; D005260:Female; D007546:Isoquinolines / Q000494:pharmacology*; D010388:Pelvis; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors* / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology; D017981:Receptors, Neurotransmitter / Q000187:drug effects* / Q000502:physiology; D012018:Reflex / Q000502:physiology*; D013127:Spinal Nerves / Q000187:drug effects* / Q000502:physiology; D013777:Tetrazoles / Q000494:pharmacology*; D014554:Urination / Q000502:physiology
chemical_list: D004338:Drug Combinations; D018691:Excitatory Amino Acid Antagonists; D007546:Isoquinolines; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D013777:Tetrazoles; D016291:Dizocilpine Maleate; C082309:tezampanel