ACPD receptors

Desai MA, Conn PJ (1991) Excitatory effects of ACPD receptor activation in the hippocampus are mediated by direct effects on pyramidal cells and blockade of synaptic inhibition. J Neurophysiol 66 40-52. 

ACPD receptors are linked by G-proteins to the phosphoinositide-protein kinase C (PI-PKC) and adenylate cyclase-cyclic AMP second messenger systems (Conn and Desai, 1991 Winder and Conn, 1992). Actions on the PI system promote the release of Ca from intracellular stores (Conn and Desai, 1991). The most selective agonist for ACPD receptors is lS,3R-trans-ACPD, although Glu, ibotenate and Quis also act at these receptors. A related class of metabotropic receptors is activated by APB. Seven different metabotropic Glu receptors (mGluRl-7) have been cloned to date (Hollmann and Heinemann, 1994 Saugstad et al.,... 

Metabotropic (ACPD) receptors have been associated with neurotoxicity that results from either activation or inhibition of receptors. Fix et al. (1993) found that infant rats injected subcutaneously with AP3 develop with an almost complete absence of optic nerves. The primary effect appears to be on the retina which shows degeneration over a period of five to seven daily AP3 injections. In the brain, the toxic effects of AP3 are largely confined to regions lacking blood-brain barriers, but some animals exhibit more distributed lesions. 

The metabotropic glutamate receptors act indirectly on ion channels via G proteins. They are selectively activated by irans-1 -amino-cyclopentyl-1,3-dicarboxylate (ACPD). These G protein-coupled receptors are either positively coupled to (ie, stimulate) phospholipase C or negatively coupled to adenylyl cyclase. Depending on the type of synapse, metabotropic glutamate receptors can initiate a slow postsynaptic excitation or a presynaptic inhibition. Although the presence of metabotropic receptors at excitatory synapses varies, most excitatory synapses contain both NMDA receptors and non-NMDA receptors in the postsynaptic membrane. 

Attwell PJE, Kaura S, Sigala G et al (1995) Blockade of both epileptogenesis and glutamate release by (15,35)-ACPD, a presynaptic glutamate receptor agonist. Brain Res 698 155-62... 

Antioxidants might be expected to be a useful tool to protect brain from toxic effects of glutamate. It was found, however, that while NMDA-antagonist orphenadrine partially protects neurons from glutamate induced toxicity both in vitro, and in vivo [36]. the agonists of metabotropic receptors, ACPD and L-AP4 [35] or lazaroid U-83836E. 

Eaton SA, Birse EF, Wharton B, Sunter DC, Udvarhelyi PM, Watkins JC, Salt TE (1993) Mediation of thalamic sensory responses in vivo by ACPD-activated excitatory amino acid receptors. Eur J Neurosci 5 186-189. 

Fig. 6. Activation of two distinct types of metabotropic glutamate receptor depresses monosynaptic reticulospinal EPSPs. Effect of (S)-2-amino-2-methyl-4-phosphonobutanoic acid (MAP4) on (1 S,3/f)-1 -aminocyclopentane-1,3-dicarboxylic acid/( 1 S,3i )-ACPD/- and L(-l-)-2-amino-4-phosphonobutyric...

ACPD, Glutamatergic receptor subtypes (1 -aminocyclopentyl -1,3-dicarboxylate) CABA b... 

In slice cultures of postnatal rat cerebellum, the glutamate receptor agonist, frans-ACPD (50 pM) induced a nearly complete loss of the dendrites of the Purkinje cells (Kapfhammer and Egle 1999). 

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