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Glutamatergic Mechanisms Controlling Lower Urinary Tract Function
Author(s) -
YOSHIYAMA Mitsuharu
Publication year - 2009
Publication title -
luts: lower urinary tract symptoms
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.451
H-Index - 15
eISSN - 1757-5672
pISSN - 1757-5664
DOI - 10.1111/j.1757-5672.2009.00043.x
Subject(s) - metabotropic glutamate receptor , metabotropic glutamate receptor 5 , glutamatergic , ampa receptor , urethral sphincter , metabotropic glutamate receptor 1 , ionotropic effect , glutamate receptor , hypogastric nerve , neurotransmission , urinary bladder , nmda receptor , chemistry , medicine , pharmacology , endocrinology , neuroscience , receptor , biology , stimulation , anatomy , urethra
Ionotropic glutamatergic antagonists for N ‐methyl‐ d ‐aspartate (NMDA) receptors or α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA) receptors administered via intravenous, intracerebroventricular, or intrathecal route increases the volume threshold for inducing micturition (V T ), decreases bladder contraction pressure, suppresses external urethral sphincter (EUS) electromyogram (EMG) activity concomitant with bladder contractions, and decreases voiding efficiency. The intrathecal injection of a metabotropic glutamate receptor (mGluR) antagonist for group I/II (mGluR1, mGluR5/mGluR2, mGluR3) facilitates EUS EMG activity without affecting bladder contractions. Mice lacking mGluR1a exhibit facilitated EUS EMG activity, which presents a prominent tonic component superimposed on bursting activity during voiding, and have larger V T than wild‐type mice. The systemic administration of an mGluR5 antagonist markedly increases V T without altering voiding pressure. These results suggest that: (i) NMDA and AMPA glutamatergic mechanisms in the central nervous system play essential roles in controlling lower urinary tract functions; (ii) the spinal mGluR1a mechanism has an inhibitory input to sphincter motor nuclei to suppress tonic EUS activity during V T ; and (iii) afferent/ascending pathways from the bladder via mGluR1a and mGluR5 are involved in mechanosensory signal transmission.