A double staining study (f1-GLAST, f2-GFAP, f3-MERGE) confirmed that GLAST was primarily located in satellite cells. were immunopositive for those glutamate transporters and for GCPII. In DRG, satellite cells were positive for GLT1 and GCPII, whereas sensory neurons were positive for EAAC1. GLAST was localized in both neurons and satellite cells. In the sciatic nerve, GLT1 and GCPII were indicated in the cytoplasm of Schwann cells, whereas GLAST and EAAC1 stained the myelin coating. Our results give for the first time a complete characterization of the glutamate transporter system in the peripheral nervous system. Therefore, they are important both for understanding glutamatergic signalling in the PNS and for creating new strategies to treat peripheral neuropathies. and models of neurological disorders, including peripheral neuropathies (Bacich et al. 2005). In addition, it appears that GCPII is definitely specifically recruited to provide a source of glutamate in hyperglutamatergic, excitotoxic conditions and would, consequently, be devoid of the side effects of glutamate antagonist medicines (Zhang et al. 2006). This has been clinically confirmed by exposing individuals to GCPII inhibitors at presumed restorative doses (vehicle der Post et al. 2005). In animal models, GCPII inhibitors reduce neuropathic pain and ectopic discharges from hurt nerves but with minor central sensitization in inflammatory and injury-induced neuropathies (Yamamoto et al. 2001; Carpenter et al. CD86 2003; Yamamoto et al. 2004). These data are in agreement with previous reports that show the ability of GCPII inhibitors to prevent pain, nerve conduction velocity reduction and nerve degeneration in diabetic BB/Wor rats (Zhang et al. 2002). Despite all these restorative attempts, little is known about the basic features of the glutamatergic Patchouli alcohol system in the peripheral nervous system (PNS). There is now growing evidence that glutamate may have a signaling function together with acetylcholine in the vertebrate neuromuscular junction (NMJ) (Rinholm et al. 2007). Some glutamate transporters (i.e. GLAST and GLT1) are located in the postsynaptic Patchouli alcohol muscle mass membrane of the NMJ of skeletal muscle mass and their presence could also be hypothesized in the Schwann cells, although with a lower denseness than in the postsynaptic sarcolemma. In agreement with the well-known CNS localization, the manifestation of GLAST, GLT1 and the neuronal glutamate transporter EAAC1 has also been recognized in rat optic nerve (Choi & Chiu, 1997). In addition, GLAST and EAAC1 seemed to be indicated in the glial and neuronal component, respectively, of dorsal root ganglia (DRG), although these results are not conclusive (Berger & Hediger, 2000; Tao et al. 2004). A deeper knowledge of the pattern of manifestation and localization of glutamate transporters and GCPII in normal PNS would allow these molecules to be used as a target for pharmacological compounds. The aim of this study is definitely to characterize the manifestation and the distribution of glutamate transporters GLT1, GLAST, EAAC1 (also known as EAAT3) and of the enzyme GCPII in rat PNS, in particular in Patchouli alcohol DRG and in myelinated fibres of the sciatic nerve. Materials and methods All the experiments involving animal care and personnel security were conducted according to the relevant standard operating procedures of the University or college of Milano-Bicocca, which were predefined based on good laboratory practice (GLP) conditions. Animal care and husbandry The care and husbandry of animals were in conformity with the institutional recommendations in compliance with national (D.L. no. 116, 1C3),.