A monoclonal antibody to alpha(2)-delta-1 revealed intense immunostaining in certain areas of rat brain, spinal cord, dorsal root ganglia, and skeletal muscle, with weaker staining in heart muscle, gut and liver. Little immunostaining was seen in spleen, kidney, thymus and lung. Staining was dense in some regions of the CNS including spinal dorsal horn anterior olfactory nucleus, anterior amygdala, basolateral (ventral)
amygdala and cortical amygdala, and the piriform, perirhinal, insular and entorhinal cortices. In hippocampus, staining Daporinad was heterogeneous with greater density in areas of glutamate terminals (mossy fiber endings on CA3 pyramidal cells and perforant path endings on granule cells and CA1 stratum radiatum). Moderate staining occurred in the lateral posterior nucleus of the thalamus, superficial layers of neocortex, periaqueductal CB-839 mw gray, substantia nigra, stria terminalis, nucleus accumbens shell and tegmental nucleus. We propose that areas of dense alpha(2)-delta-1 staining in brain and spinal cord are likely sites of action for the analgesic, anticonvulsant and anxiolytic-like actions of pregabalin and gabapentin in animal models. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Even though it is generally thought that umami stimuli such as monosodium glutamate (MSG) and sweet stimuli such as sucrose are
detected by different taste receptors, these stimuli appear to share taste qualities when amiloride
(a sodium channel blocker) is present to reduce PD-1/PD-L1 Inhibitor 3 order the sodium taste. Single fiber recording studies of the facial and glossopharyngeal nerves have shown that encoding Of L-2-amino-4-phosphonobutyrate (L-AP4), a potent mGluR4 agonist that elicits a taste quite similar to MSG, may occur in the same fibers that also encode sweet stimuli. This suggests that L-AP4 and sweet substances may activate common receptors or afferent signaling mechanisms. We report results of behavioral experiments that test this hypothesis. In the first study, rats conditioned to avoid sucrose or L-AP4 generalized the aversion to the opposite substance, indicating that both substances elicited similar tastes. However, two taste discrimination experiments showed that rats easily discriminated between sucrose and L-AP4 over a wide range of concentrations, even when the cue function of sodium associated with L-AP4 was reduced by amiloride and neutralized by adding equimolar concentrations of NaCl to sucrose. These data suggest that even though L-AP4 and sucrose elicit similar taste qualities, one or both substances also elicit other taste qualities not shared by the opposite substance. They also suggest that the taste-mGluR4 receptor and the signal pathway activated by L-AP4 are not the same as those activated by sucrose.