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Johnson PJ, Bornstein JC: Neurokinin-1 and -3 receptor blockade inhibits slow excitatory synaptic transmission in myenteric neurons and reveals slow inhibitory input. Neuroscience. 2004;126(1):137-47.
Recent studies have shown that tachykinins mediate slow synaptic transmission to myenteric AH (afterhyperpolarising) neurons via neurokinin-3 receptors (NK (3) R). This study investigated a similar role for neurokinin-1 receptors (NK (1) R) and compared the effect of selective receptor antagonists on non-cholinergic slow excitatory post-synaptic potentials (EPSPs) recorded in myenteric AH neurons of the guinea-pig ileum. Slow EPSPs evoked by electrical stimulation of circumferentially oriented presynaptic nerves were mimicked by application of senktide, an NK (3) R agonist. [Sar (9),Met (O (2))(11)]-substance P, an NK (1) R agonist, depolarised a smaller number of neurons. SR142801, a selective NK (3) R antagonist (100 nM), inhibited slow EPSPs and responses to senktide, but had no effect on depolarisations evoked by forskolin, an activator of adenylate cyclase. SR140333, a selective NK (1) R antagonist, inhibited slow EPSPs in a subset of neurons and blocked responses to [Sar (9),Met (O (2))(11)]-substance P, but not to senktide or forskolin. Slow EPSPs that were predominantly mediated by NK (1) R had significantly shorter latencies than those due to activation of NK (3) R. After blockade of slow EPSPs, slow hyperpolarizing responses to presynaptic nerve stimulation were revealed in one-third of neurons. These events, which were associated with a decrease in input resistance and blocked by tetrodotoxin, were equated with slow inhibitory postsynaptic potentials. They were abolished by the 5-hydroxytryptamine (1A) receptor antagonist 1-(2-methoxyphenyl)-4-[4-(2-phthalimido) butyl]-piperazine (NAN-190), but unaffected by phentolamine, an alpha-adrenoceptor antagonist. In conclusion, these results provide the first direct evidence that NK (1) R mediate some slow excitatory synaptic input to myenteric AH neurons, and suggest that NK (1) R and NK (3) R activate distinct signal transduction pathways. These results also demonstrate that slow inhibitory synaptic transmission, which may be mediated by 5-hydroxytryptamine, is more prevalent in the myenteric plexus than previously indicated. |
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