Abstract
Vasoactive intestinal peptide (VIP) immunoreactive secretomotor neurons in the submucous plexus are involved in mediating bacterial toxin-induced hypersecretion leading to diarrhoea. VIP neurons become hyperexcitable after the mucosa is exposed to cholera toxin, which suggests that the manipulation of the excitability of these neurons may be therapeutic. This study used standard intracellular recording methods to systematically characterize slow excitatory postsynaptic potentials (EPSPs) evoked in submucosal VIP neurons by different stimulus regimes (1, 3 and 15 pulse 30 Hz stimulation), together with their associated input resistances and pharmacology. All slow EPSPs were associated with a significant increase in input resistance compared to baseline values. Slow EPSPs evoked by a single stimulus were confirmed to be purinergic, however, slow EPSPs evoked by 15 pulse trains were non-purinergic and those evoked by 3 pulse trains were mixed. NK1 or NK3 receptor antagonists did not affect slow EPSPs. The group I mGluR receptor antagonist, PHCCC reduced the amplitude of purinergic and non-purinergic slow EPSPs. Blocking mGluR1 receptors depressed the overall response to 3 and 15 pulse trains, but this effect was inconsistent, while blockade of mGluR5 receptors had no effect on the non-purinergic slow EPSPs. Thus, although other receptors are almost certainly involved, our data indicate that there are at least two pharmacologically distinct types of slow EPSPs in the VIP secretomotor neurons: one mediated by P2Y receptors and the other in part by mGluR1 receptors.
Highlights
Vasoactive intestinal peptide (VIP) immunoreactive neurons in the submucous plexus are the key secretomotor neurons in the enteric nervous system (Bornstein and Furness, 1988)
A total of 213 neurons were impaled in 67 preparations and 72 neurons were studied in detail as they had stable impalements and displayed slow excitatory postsynaptic potentials (EPSPs)
28 of the 69 neurons with inhibitory postsynaptic potentials (IPSPs) were filled with biocytin, all were immunoreactive for VIP
Summary
Vasoactive intestinal peptide (VIP) immunoreactive neurons in the submucous plexus are the key secretomotor neurons in the enteric nervous system (Bornstein and Furness, 1988) Their importance is shown by their involvement in the hypersecretion produced by cholera toxin and Escherichia coli enterotoxins (Banks et al, 2005), the fact that they are the only secretomotor neurons to receive input from outside the intestine and their converging input from many different enteric neurons (Bornstein and Furness, 1988). These neurons exhibit several excitatory and inhibitory potentials identified by their time courses and neurotransmitters (Gwynne and Bornstein, 2007). Another complication comes from the report that some submucosal neurons are depolarized by the NK1 receptor agonist septide, but are not immunoreactive for NK1 tachykinin receptors (Moore et al, 1997)
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