Presynaptic α₂-adrenoceptors inhibit excitatory synaptic transmission in rat brain stem

The synaptic connection between the commissural portion of the nucleus tractus solitarius (ComNTS) and the dorsal motor nucleus of the vagus (DMV) was studied in rat brain stem slices, using the patch-clamp technique. The excitatory postsynaptic currents (EPSC) evoked by stimulation of the ComNTS were blocked by kynurenic acid (1 mM) and, in Mg²⁺-free solution, were sensitive to both the N-methyl-D-aspartic acid (NMDA) receptor blocker 3- [(RS)-2-carboxypiperazine-4-yl]-propyl-1-phosphonic acid (20 μM) and the non-NMDA receptor blocker 2,3-dihydro-6-nitro-7-sulfamoyl- benzo(f)quinoxaline (5 μM). Norepinephrine (NE, 1-100 μM) inhibited the EPSC, and the inhibition was attenuated by the α₂-adrenoceptor antagonists idazoxan (1 μM) and yohimbine (10 μM) but not by the β-adrenoceptor antagonist nadolol (50 μM). The NE-releasing agent tyramine (100 μM) reduced the EPSC, and the inhibition was attenuated by 1 μM idazoxan. NE (30 μM) did not affect the membrane input resistance but reduced the paired- pulse depression, demonstrating that NE acts on presynaptic α₂- adrenoceptors. The results indicate the existence of a glutamatergic pathway from the ComNTS to the DMV neurons modulated by presynaptic NE receptors. This pathway might be a component of the vagovagal reflex regulating gastrointestinal function.