There is increasing evidence that the excitatory neurotransmitter glutamate has an important function in the peripheral nervous system, specifically in modulating mechanosensitivity1, in addition to its well established role as a transmitter in the central nervous system. We are using stretch-sensitive annulospiral afferent nerve endings in muscle proprioceptors (muscle spindles) to explore this system. The endings contain synaptic levels of glutamate and express glutamate transporters, as well as proteins involved in Ca2+-mediated exocytosis. Exogenous glutamate increases stretch-evoked firing while glutamate receptor antagonists or blockade of exocytosis inhibit, or even entirely abolish, firing. This suggests the expression of a glutamate receptor on these nerve endings1. However, the receptor shows an atypical pharmacological profile2. The drug effects on afferent nerve response most closely match the pharmacological profile of the phospholipase D-coupled metabotropic glutamate receptor (mGluR), reported by a number of groups in the hippocampus 3,4. However, it has never been isolated, sequenced or characterised. Based on its pharmacological profile, this atypical mGluR is either an uncharacterised splice variant, or an entirely novel mGluR. Pharmacology suggests it is the only mGluR expressed in the spindle, therefore stretch-sensitive nerve endings are an ideal source for receptor isolation and characterisation.The rat deep masseter muscle has been identified as a rich source of muscle spindles 5, from which we have developed a method of nerve ending extraction to isolate and characterise the atypical mGluR. Deep masseter muscles were removed from adult male Sprague Dawley rats (weight 200 – 450g) and euthanised by CO2 overdose (in accordance with EU Legislation, 2013). Spindles were dissociated from the tissue by collagenase digestion and then identified by staining with methylene blue (Figure 1). Screening techniques included Western blotting, mass spectrometry and immunohistochemistry. Current results suggest that the atypical mGluR may be a splice variant of mGluR5, based on Western blotting (Figure 2). A strong band of approximately 102 kDa was observed, whereas the band in the hippocampus was approximately 150 kDa, consistent with the expected molecular weight. No consistent labelling was seen for mGluR1, mGluR2, mGluR3, mGluR4, mGluR6, mGluR7 or mGluR8 in muscle spindles (n=3 for each). Mass spectrometry has revealed abundant spindle and synaptic proteins in whole tissue homogenates. Candidate channels thought to play a role in mechanotransduction are also being sought in our screening process. Progress to date and preliminary findings on these studies will be reported.