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EFFECTS OF
A SELECTIVE METABOTROPIC GLUTAMATE RECEPTOR AGONIST ON THE MICTURITION
REFLEX PATHWAY IN URETHANE-ANESTHETIZED RATS
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Authors:
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H.Tanaka, H.Kakizaki,
S.Matsura.T.Mitui, N.Yamashita, K.Ameda, T.Koyanagi
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Institution:
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Department of Urology,Hokkaido
University School of Medicine
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Aims of
study:
Glutamate receptors (GluR) can be broadly classified as ionotrpic GluR that
are ligand-gated ion channels and metabotropic GluR that are coupled to GTP
binding protein. Previous studies revealed that glutamate is an important transmitter
in the central neural pathways in controlling lower urinary tract function.
Ionotropic GluR (e.g. NMDA receptors and AMPA / kinate receptors) were proved
to be involved in the descending and ascending limb of micturition reflex pathway
between lumbosacral spinal cord and pontine micturition center [1.2]. The aim
of this study was to determine the role of metabotropic GluR in spinobulbospinal
micturition reflex, using a selective metabotropic GluR agonist,trans-(+/-)-1-Amino1,3-cyclopentanedicarboxylic
acid (trans-ACPD).
Methods:
Experiments were performed on 28 Wistar rats anesthetized with subcutaneous
injection of urethane (1.2 gm./kg.). A cystostomy catheter was inserted from
the bladder dome to monitor the bladder pressure and an intrathecal (i.t.) catheter
was implanted for administration of the drugs. The amplitude of rhythmic bladder
contractions (RBC) evoked by bladder distention under isovolumetric condition
as well as the amplitude of bladder contraction elicited by electrical stimulation
of pontine micturition center (PMC) were investigated before and after i.t.
injection of trans-ACPD, respectively. The effect of trans-ACPD on the urethral
activity during isovolumetric bladder contraction was also examined by using
urethral perfusion pressure and electromyography of the external urethral sphincter
(EUS).
Results:
I.t. injection of trans-ACPD (3 -10 *g) completely inhibited RBC evoked by bladder
distension and the duration of inhibition was dose-dependent (3 *g: 11.4+/-5.5min,
5 *g: 13.2+/-2.5min, 10 *g: 34.8+/-5.1min). The amplitude of bladder contraction
evoked by electrical stimulation of PMC was decreased to 12.4+/-8.7% of control
by trans-ACPD (10 *g i.t.). In addition, bursting activity of EUS and corresponding
high frequency oscillation of urethral pressure during isovolumetric bladder
contraction were completely abolished by trans-ACPD (10 *g i.t.).
Conclusions:
The present experiments indicated that i.t. administration of a selective metabotropic
glutamate receptor agonist to lumbosacral spinal cord