GABA receptors striatal

Muscarinic and dopaminergic pathways in the CNS interact in control of numerous pathways implicated in diseases, especially those controlling involuntary motor systems. Muscarinic effects on dopamine release are mediated in several ways via different mAChR subtypes. Thus mAChR facilitation of DA release appears to involve M4 receptors on GABA projection neurons to the striatum, while M3 receptors on striatal DA neurons are predicted to inhibit striatal DA release [12],... 

In addition to presynaptic receptors, autoradiographic studies have indicated the presence of postsynaptic H3-receptor binding sites as well. Chemical destruction of postsynaptic structures in the striatum using quinolinic and kainic acid resulted in a marked decrease of striatal H3-receptor binding sites (Cumming et al., 1991 Pollard et al., 1993 Ryu et al., 1994). Consequently, a major part of the striatal H3-receptors may be located on striatal GABA neurons, representing more than 85% of the striatal efferents (Kita Kitai, 1988). 

Although striatal 5-HT4 receptors, when activated, facilitate dopamine release, the receptors probably are located on striatal GABA neurons, so the receptors have not been entered in Table 4 (see Eglen et al. 1995). 

Kirk IP, Richardson PJ (1994) Adenosine A2a receptor-mediated modulation of striatal [3H]GABA and [3H]acetylcholine release. J Neurochem 62 960-6 Koch H, von Ktigelgen I, Starke K (1997) P2-receptor-mediated inhibition of noradrenaline release in the rat hippocampus. Naunyn-Schmiedeberg s Arch Pharmacol 355 707-15 Koch H, von Ktigelgen I, Starke K (1998) P2-receptor-mediated inhibition of noradrenaline release in the rat pancreas. Naunyn-Schmiedeberg s Arch Pharmacol 357 431 10 Koizumi S, Inoue K (1997) Inhibition by ATP of calcium oscillations in rat cultured hippocampal neurones. Br J Pharmacol 122 51-8... 

With regard to the neurotransmitters involved in these circuits, the striatal neurons are mainly GABAergic and they also contain met-enkephalin as a co-transmitter as part of the indirect pathway D2 receptors are also present. In the direct pathway, in addition to GABA, dynorphin and substance P act as co-transmitters D, receptors are predominant in the direct pathway. 

Application of a D1 receptor agonist reduces GABA-evoked currents in neurons from the striatum or olfactory bulb (Brunig et al., 1999 Flores-Hernandez et al., 2000). This effect, in striatal medium spiny neurons, is mediated through the activation of PKA/DARPP-32/ PP-1 cascade, since it is blocked by an inhibitor of PKA or by the absence of DARPP-32 in mutant mice while it is mimicked by inhibitor of PP-1 (Flores-Hernandez et al., 2000). Stimulation of the D1 receptor induces a phosphorylation of (32/(33 GABAa... 

Yan Z, Surmeier DJ (1997) D5 dopamine receptors enhance Zn2+-sensitive GABA(A) currents in striatal cholinergic interneurons through a PKA/PP1 cascade. Neuron 79 1115-1126. 

Levey et al. (1993) found that axon terminals immunoreactive for D1 and D2 receptor proteins formed symmetrical synapses exclusively, and primarily with unlabeled dendritic shafts. In cultures, D1 and D2 receptors have been colocalized to terminals of intrinsic neurons (Wong et al., 1999). Functional D1 receptors have also been demonstrated on the terminals of striatal cells in the substantia nigra (Fiorillo and Williams, 1998). Collectively, the results for D1 and D2 receptors suggest their presence on the terminals of intrinsic GABA neurons. 

Stefani A, Pisani A, Mercuri NB, Bernard G, Calabresi P (1994) Activation of metabotropic glutamate receptors inhibits calcium currents and GABA-mediated synaptic potentials in striatal neurons. J Neurosci 74 6734-6743. 

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