The role played by glutamate in the mechanism and progression of PD via various ionotropic and
metabotropic receptor types in the basal ganglia motor loop has been extensively investigated.
CB1 is a
metabotropic receptor of seven transmembrane domains attached to a [G.sub.i/o] protein.
The models include an intravascular photochemical reaction that occludes blood vessels, producing spinal cord ischemia with subsequent trunk mechanical allodynia [18, 19]; anterolateral lesions of the spinal cord in monkeys and rats that produce overgrooming and mechanical allodynia [20, 21]; a clip compression model in which the thoracic spinal cord is compressed by 35 g or 50 g clip demonstrates mechanical hyperalgesia in the hindlimbs [22]; quisqualic acid (an AMPA/kainate and a group I glutamate
metabotropic receptor agonist) injection into the dorsal horn produces overgrooming [23]; and a spinal hemisection [24, 25] and spinal contusion models [26-28] demonstrate mechanical allodynia in both the hindlimbs and forelimbs.
It is of great importance to investigate the extent to which the blockade of the
metabotropic receptor 5 affects the imbalance between direct and indirect pathways and to investigate what the molecular alterations in the mGluR5-related signaling pathway are, in order to interpret the antidyskinesia effect of the antagonists of mGluR5.
Opioid receptors are
metabotropic receptor coupled to Gi protein.
Similarly, the effect of a single spike of fast inhibitory synapse through [GABA.sub.A] and slow inhibitory response through
metabotropic receptor [GABA.sub.B] is depicted in Figure 3B.
Glutamate can also bind to a
metabotropic receptor.
Metabotropic receptors are both slower and longer acting than ionotropic receptors, for they activate a second messenger cascade system that can result in the opening of ion channels located elsewhere on the same postsynaptic membrane.
[+ or -] i.q.r, median [+ or -] inter-quartile range; mGluR,
metabotropic receptor; NMDA, N-methyl-D-aspartate; NMDAR, NMDA receptor; P/CB, average number of pulses per contraction burst; PLP, pre-locomotor pulse; pT, pre-treatment period; RP, rhythmic potential; SUBP, small, uncorrelated body pulse; SUTP, small, uncorrelated tentacle pulse; T1, treatment period 1; T2, treatment period 2; TP, tentacle pulse.
[D.sub.1] is a G-protein-coupled
metabotropic receptor that increases activity of the enzymes adenylyl cyclase and phospholipase C.
On the whole, pharmacological profile identified mGluR5 as the
metabotropic receptor subtype that is implicated in the glutamate release response to glutamatergic stimulation.
Martorana et al., "Oligodendrocytes express P2Y12
metabotropic receptor in adult rat brain," Neuroscience, vol.
Astrocytes express a neurotransmitter receptor called G-protein coupled
metabotropic receptor (GPCR).
