Co-localize with NMDA TRXR1/TXNRD1 Protein Molecular Weight receptors through the dystrophin lycoprotein complex at the NMJs of rat and mouse skeletal muscle (Grozdanovic Gossrau, 1998). Interestingly, levels of NOS-I are significantly decreased within the junctional sarcolemma of muscle tissues from patients2013 The Authors. The Journal of PhysiologyC2013 The Physiological SocietyC. Lindgren and othersJ Physiol 591.with Duchenne muscular dystrophy, in whom the protein dystrophin is mutated (Brenman et al. 1995). Despite a potentially prominent part for NMDA receptors in activating NO synthesis in the NMJ, the supply with the endogenous NMDA agonist is unknown. Cathepsin D Protein Species glutamate is a most likely candidate and has extended been recognized to become present at the NMJ, in both the nerve terminals and PSCs (Waerhaug Ottersen, 1993). On the other hand, the mechanism by which glutamate could be released into the synaptic cleft is unclear. Pinard and Robitaille (2008) make a robust argument that glutamate is released in the PSCs in a frequency-dependent manner, however they also concede that glutamate could be released in the nerve terminals. The discovery on the dipeptide N -acetylasparty lglutamate (NAAG) in addition to its hydrolytic enzyme, glutamate carboxypeptidase-II (GCP-II), in the vertebrate NMJ (Berger et al. 1995; Walder et al. 2013) suggests a third possibility. We recently showed that NAAG is released from lizard motor nerve terminals throughout high-potassium depolarization or electrical stimulation in the motor nerve (Walder et al. 2013). GCP-II, which can be present on the extracellular surface from the PSCs (Walder et al. 2013), could be anticipated to hydrolyse released NAAG to N -acetylaspartate and glutamate. Glutamate made in this way could stimulate NO synthesis by activating the NMDA receptor in the muscle end-plate. Much more work is necessary to explore this novel suggestion.method, but will call for chemical analysis (as in Hu et al. 2008). Interestingly, if PGE2 -G would be the sole signalling molecule accountable for the delayed muscarine-induced enhancement, this raises the query as towards the supply of 2-AG. Since COX-2 is located within the PSCs, the 2-AG ought to either be transported into the PSCs soon after getting released in to the synaptic cleft from the muscle or it should be synthesized separately inside the PSC. The observation that the delayed muscarine-induced enhancement of neurotransmitter release isn’t prevented by blocking M3 receptors (Graves et al. 2004), that are responsible for the synthesis and release of 2-AG in the muscle (Newman et al. 2007), supports the latter suggestion. Even so, it is actually also attainable that blocking M3 receptors reduces 2-AG to a level under that expected to make observable depression but sufficient to serve as a substrate for PGE2 -G production. Further experiments are necessary to identify which pool of 2-AG is really used for the synthesis of PGE2 -G.The PGE2 -G receptorIs PGE2 -G an endogenous modulator in the NMJ?Though the requirement for COX-2 in the muscarine-induced enhancement of neurotransmitter release is very clear, the proof that PGE2 -G could be the sole or primary product of COX-2 responsible for synaptic enhancement has significantly less assistance. The proof for this proposition comes from our observations that: 2-AG is present in the NMJ (Newman et al. 2007), PGE2 -G mimics the delayed enhancement (Fig. three) and its inhibitor, capsazepine, blocks the muscarine-induced enhancement (Fig. 5). Even so, it can be possible that COX-2 produces other signalling molecules that improve neurotransmitter release in.
