Only a few agonists exhibit selectivity between the AMPA and the kainate subtypes of the glutamate receptor. The most commonly used kainate receptor preferring agonist, (S)-2-amino-3-(5-tert-butyl-3-hydroxy-4-isoxazolyl)propionic acid [(S)-ATPA], is an (R,S)-2-amino-3-(5-methyl-3-hydroxy-4-isoxazolyl)propionic acid (AMPA) derivative in which the methyl group at the 5-position of the isoxazole r...

BACKGROUND The alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subtype of glutamate receptor mediates fast excitatory neurotransmission in the central nervous system. Many general anesthetics inhibit AMPA receptors in vitro; however, it is not certain if this inhibition contributes to the behavioral properties of these drugs. AMPA receptors lacking the GluR2 subunit are resistan...

Costanza Angelini, Alessandro Morellato, Annalisa Alfieri, Lisa Pavinato, Tiziana Cravero, et al. (see pages [7183–7200][1]) The postsynaptic density (PSD) of excitatory synapses contains an extraordinary number proteins, including AMPA and NMDA receptors, accessory proteins that regulate

Na(+)-activated K(+) (K(Na)) channels are expressed in neurons and are activated by Na(+) influx through voltage-dependent channels or ionotropic receptors, yet their function remains unclear. Here we show that K(Na) channels are associated with AMPA receptors and that their activation depresses synaptic responses. Synaptic activation of K(Na) channels by Na(+) transients via AMPA receptors sha...

In vivo microdialysis was used to study the effects of morphine on glutamate release from the ventral tegmentum area (VTA) in freely moving rats. Intraperitoneal (i.p.) injection of acute and repeated morphine at increasing doses significantly enhanced glutamate release. Only a minor tolerance developed to this dosage of morphine. AP-S (2-amino-5-phosphonovaleric acid, 0.5 mg/kg i.p.), a N...

Phosphorylation of glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors by Protein Kinase A (PKA) is known to regulate AMPA receptor (AMPAR) trafficking and stabilization at the postsynaptic membrane, which in turn is one of the key mechanisms by which synaptic transmission and plasticity are tuned. However, not much is known as to how Gs-coupled receptors contribute ...

Ca(2+)-permeable AMPA receptors are densely expressed in the spinal dorsal horn, but their functional significance in pain processing is not understood. By disrupting the genes encoding GluR-A or GluR-B, we generated mice exhibiting increased or decreased numbers of Ca(2+)-permeable AMPA receptors, respectively. Here, we demonstrate that AMPA receptors are critical determinants of nociceptive p...

Calcium and chloride ions stimulated [3H]glutamate binding to quisqualate-sensitive [3H]glutamate binding sites 4-fold, as measured by quantitative autoradiography, whereas 100 mM potassium thiocyanate had no additional effect. In contrast, calcium and chloride had little effect on the binding of [3H](RS)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid ([3H]AMPA), but 100 mM thiocyanat...

Previously, we have shown that the phosphoinositide-3-kinase (PI3K) mediated acute (24 h) post-conditioning neuroprotection induced by propofol. We also found that propofol post-conditioning produced long term neuroprotection and inhibited the internalization of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluR2 subunit up to 28 days post middle cerebral artery occlusion...