GluR-A and GluR-B AMPA receptor subunits and NR1 but not NR GluR-A and GluR-B AMPA receptor subunits and NR1 but not NR2 NMDA receptor subunits (566). Conversely, motoneurons inside the urethral sphincter nucleus express all 4 AMPA receptor subunits (GluR-A, -B, -C, and -D) in conjunction with moderate amounts of NR2A and NR2B too as high levels of NR1 receptor subunits. It seems most likely that thisCompr Physiol. Author manuscript; obtainable in PMC 2015 June 25.de Groat et al.Pagedifference in expression accounts for the distinct sensitivity of bladder and sphincter reflexes to glutamatergic antagonists. Glutamate also plays a role as an excitatory transmitter in the afferent limb from the micturition reflex. C-fos expression induced in spinal interneurons by activation of bladder afferents is suppressed by the administration of each NMDA and non-NMDA glutamatergic receptor antagonists (55,298,300). In contrast to excitatory effects of glutamate via ionotropic glutamatergic receptors (NMDA and AMPA/kinate), activation metabotropic glutamatergic receptors (mGluRs) in the spinal cord has Ption.1Towhom correspondence needs to be addressed. E-mail: [email protected] inhibitory effects on the descending limb in the micturition reflex since a group I/II mGluR agonist applied to the spinal cord in the lumbosacral level suppresses reflex bladder contractions as well as these induced by PMC stimulation in rats (621). It has also been reported that mGluRs are involved in inhibition on the excitatory pathway to the EUS simply because a group I/II mGluR antagonist applied in to the lumbosacral intrathecal space considerably facilitates the EMG activity in the EUS in rats (719). For the duration of synaptic transmission, glutamate released from presynaptic nerve terminals is cleared in the synaptic cleft into presynaptic nerve terminals and adjacent astrocytes, via glutamate transporters. A recent study demonstrated that intrathecal application of a nonselective inhibitor of glutamate transporters, L-trans-pyrrolidine-2,4-dicarboxylic acid (L-trans-PDC) that increases endogenous glutamate concentration at nerve terminals, delays the onset of micturition by increasing intermicturition intervals and stress thresholds in rats below urethane anesthesia (273). Inhibitory amino acids (GABA, glycine, and glycine transporter)--Intrathecal injection of either GABAA or GABAB agonists increases bladder capacity and decreases voiding stress and efficiency in standard rats (279, 501) and also suppresses DO in rats induced with intravesical application of oxyhemoglobin, an NO scavenger (501) or spinal cord injury (435). In addition, intravenous or intrathecal application of a GABA reuptake inhibitor (tiagabine) that increases endogenous GABA concentrations reportedly inhibits regular micturition in rats (500). In a little clinical study in 3 subjects, intrathecal administration of a GABAB receptor agonist (baclofen) increased the volume threshold for inducing the micturition reflex (89). Intrathecally administered baclofen also created phaclofen-sensitive inhibition of distention-evoked micturition in conscious rats that appears to become resistant to capsaicin (substance P depletion) and parachlorophenylalanine (5hydroxytryptamine depletion) pretreatment (234). Due to the fact baclofen also inhibits field stimulation-evoked release of CGRP from primary afferent terminals in dorsal horn slices, 1 probable mechanism of action of GABAergic inhibition is suppression of transmitter release from principal afferent terminals inside the spinal cord. Preceding studies also showed that glycine, one more inhibitory amino acid, acting on.