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OtherAUTONOMIC PHARMACOLOGY

Role of Spinal Glutamatergic Transmission in the Ascending Limb of the Micturition Reflex Pathway in the Rat

Hidehiro Kakizaki, Mitsuharu Yoshiyama, James R. Roppolo, August M. Booth and William C. De Groat
Journal of Pharmacology and Experimental Therapeutics April 1998, 285 (1) 22-27;
Hidehiro Kakizaki
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Mitsuharu Yoshiyama
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James R. Roppolo
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August M. Booth
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William C. De Groat
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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 μV) 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 μg), a competitive α-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 μg of LY215490, respectively. The i.t. administration of MK-801 (1–100 μg), 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 μg of MK-801, respectively. Combined administration of LY215490 (0.1 μg) and MK-801 (1 μg), 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.

Footnotes

  • Send reprint requests to: William C. de Groat, Ph.D., Department of Pharmacology, University of Pittsburgh School of Medicine, W1357 Biomedical Science Tower, Pittsburgh, PA 15261.

  • ↵1 This work was supported by National Institutes of Health Grants DK-49430 (W.D.) and DK-51402 (W.D.).

  • ↵2 Present address: Department of Urology, Hokkaido University School of Medicine, Sapporo, 060 Japan.

  • Abbreviations:
    AMPA
    α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid
    NMDA
    N-methyl-d-aspartate
    PMC
    pontine micturition center
    CSF
    cerebrospinal fluid
    PLN
    pelvic nerve
    PAG
    periaqueductal gray
    CNS
    central nervous system
    i.t.
    intrathecal
    • Received April 24, 1997.
    • Accepted November 28, 1997.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 285, Issue 1
1 Apr 1998
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OtherAUTONOMIC PHARMACOLOGY

Role of Spinal Glutamatergic Transmission in the Ascending Limb of the Micturition Reflex Pathway in the Rat

Hidehiro Kakizaki, Mitsuharu Yoshiyama, James R. Roppolo, August M. Booth and William C. De Groat
Journal of Pharmacology and Experimental Therapeutics April 1, 1998, 285 (1) 22-27;

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OtherAUTONOMIC PHARMACOLOGY

Role of Spinal Glutamatergic Transmission in the Ascending Limb of the Micturition Reflex Pathway in the Rat

Hidehiro Kakizaki, Mitsuharu Yoshiyama, James R. Roppolo, August M. Booth and William C. De Groat
Journal of Pharmacology and Experimental Therapeutics April 1, 1998, 285 (1) 22-27;
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