Tests of the roles of two diffusible substances in long-term potentiation: evidence for nitric oxide as a possible early retrograde messenger.

摘要: Abstract Although long-term potentiation (LTP) in the CA1 region of hippocampus is initiated postsynaptically by influx Ca2+ through N-methyl-D-aspartate receptor channels, maintenance LTP seems to be at least part presynaptic. This suggests that postsynaptic cell releases a retrograde messenger activate presynaptic terminals. It likely this membrane-permeant and reaches neuron diffusion. We therefore have investigated two major candidate messengers, arachidonic acid nitric oxide (NO). Consistent with or lipoxygenase metabolite being messenger, phospholipase A2 inhibitor nordihydroguaiaretic blocked guinea pig vitro. However, (up 100 microM) did not reliably produce activity-independent LTP, activity-dependent was DL-aminophosphonovaleric acid. Since also interferes signal transduction involving NO, we next examined whether inhibitors NO synthase block LTP. NG-Nitro-L-arginine when given bath, inhibition partially overcome high concentrations L-arginine, suggesting specific synthase. NG-methyl-L-arginine (but NG-methyl-D-arginine) injected intracellularly, indicating located cell. The turn, released into extracellular space, since bathing slice hemoglobin, protein binds taken up cells, Moreover, enhances spontaneous release transmitter from hippocampal neurons dissociated culture. These data favor idea might