Role of spinal glutamatergic transmission in the ascending limb of the micturition reflex pathway in the rat.
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.
Kakizaki
H
H
Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
Yoshiyama
M
M
Roppolo
J R
JR
Booth
A M
AM
De Groat
W C
WC
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
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