Role of nmda and ampa glutamatergic transmission in spinal c-fos
expression after irritation of urinary tract.
Kakizaki, Hidehiro, Mitsuharu Yoshiyama, and William C. De Groat.
Department of Pharmacology, University of Pittsburgh, School of
Medicine, Pittsburgh, PA 15261, U.S.A.
APStracts 2:0335R, 1995.
Chemical irritation of the lower urinary tract (LUT) of the rat
increases the expression of the immediate early gene c-fos within
neurons in the dorsal horn (DH), dorsal commissure (DCM) and
intermediolateral region including sacral parasympathetic nucleus
(SPN) of the spinal cord (L6-S1). A previous study indicated the
involvement of the N-methyl-D-aspartate (NMDA) receptor in this c-fos
expression following LUT irritation. The role of glutamatergic
synapses was further investigated using a selective and competitive
alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA) receptor
antagonist (LY 215490). Systemic administration of LY 215490 produced
a dose-dependent decrease in the number of Fos-positive cells
following LUT irritation in the DCM and SPN areas, while in the DH
only the highest dose (10 mg/kg) of LY 215490 decreased the number of
Fos-positive cells. A low dose (1 mg/kg) of either MK-801 (an NMDA
antagonist) or LY 215490 alone did not alter c-fos expression.
However, a combined administration of low doses of MK-801 and LY
215490 significantly decreased the number of Fos-positive cells in
all regions of the spinal cord. These results indicate that AMPA as
well as NMDA receptors are involved in the spinal processing of
nociceptive input from the LUT and that these glutamatergic receptors
play a synergistic role in visceral nociceptive processing.
Received 19 July 1995; accepted in final form 7 November 1995.
APS Manuscript Number R450-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 December 95