Y₂‐receptor‐mediated selective inhibition of slow, inhibitory postsynaptic potential in submucous neurones of guinea‐pig caecum

Abstract

4 In concentrations of up to 300 nM, NPY and its analogues had no depressant effects on the active and passive properties of the impaled neurone and did not affect the amplitude or duration of either cholinergic fast synaptic potentials or non-cholinergic, slow excitatory postsynaptic potentials (e.p.s.ps). Furthermore, none of these peptides altered the amplitude or time-course of changes in membrane potential induced by focal application of acetylcholine or noradrenaline. 5 It is, therefore, concluded that the selective inhibition of the slow i.p.s.p. is mediated by Y2-receptors, located presynaptically on noradrenergic nerve terminals.

Presynaptic calcium channels mediating synaptic transmission in submucosal neurones of the guinea‐pig caecum

“…Repetitive focal stimulation with five pulses at 40 Hz evoked a slow IPSP of 29 ± 0.4 mV (17‐35 mV, n = 81) amplitude, which was well maintained for > 6 h (see Fig. 1 of Cunningham, Mihara & Lees, 1994). In all neurones tested ( n = 50), superfusion of the N‐type calcium channel inhibitor ω‐CTX GVIA (3‐300 nM) was observed to suppress the amplitude of the slow IPSP (Fig.…”

“…In contrast, our results suggest that inhibition of only the N‐type calcium channel is sufficient to suppress completely the noradrenergic slow inhibitory transmission mediated through activation of extrinsic pathways. In this regard, it is interesting that the slow IPSP is completely suppressed by muscarine (North, Slack & Surprenant, 1985), adenosine (Barajas‐Lopez, Surprenant & North, 1991), and neuropeptide Y (Cunningham, Mihara & Lees, 1994). Thus, presynaptic neuromodulation mediated through inhibition of N‐type calcium channels may be an important means of altering the integration of synaptic signals through different neuronal pathways in the submucosal plexus of the guinea‐pig caecum.…”

The regulation of veratridine‐stimulated electrogenic ion transport in mouse colon by neuropeptide Y (NPY), Y1 and Y2 receptors

“…Addition of BIIE0246 to rat hypothalamic slices after neuronal stimulation ( King et al ., 2000 ), and following electrical field stimulation of spleen and kidney sympathetic nerves ( Malmström et al ., 2002a ) results in a significant increase in NPY release. Previous studies have demonstrated a role for Y 2 receptor‐mediated blockade of inhibitory postsynaptic potentials in guinea pig submucosal neurons ( Cunningham et al ., 1994 ). Therefore, increased NPY release in the presence of BIIE0246 could subsequently inhibit the release of an antisecretory neurotransmitter (e.g.…”

“…The decrease in veratridine‐stimulated secretion that we observed was unexpected, as NPY added to rat ( Cox & Cuthbert, 1988 ) and mouse ( Holliday et al ., 2000 ; Cox et al ., 2001 ) colon mucosae is antisecretory and causes prolonged, concentration‐dependent decreases in I sc . In the guinea pig ENS however, Y 2 receptors have been implicated in the attenuation of inhibitory postsynaptic potentials in caecal submucosal neurons ( Cunningham et al ., 1994 ). This could offer a potential explanation for the significant decrease in veratridine‐induced secretion in NPY−/− mouse colon.…”

Functional consequences of neuropeptide Y Y2 receptor knockout and Y2 antagonism in mouse and human colonic tissues

“…In the hypothalamus, activation of Y 2 receptors inhibits NPYmediated tonic inhibition of adjacent pro-opiomelanocortin (POMC) neurones leading to satiety in mouse and man (Batterham et al, 2002). In the peripheral nervous system, Y 2 receptors also provide significant presynaptic (or prejunctional) inhibition that can either be autoinhibitory (Mal-mstro¨m et al, 2002), inhibitory upon noradrenergic (Cunningham et al, 1994) or cholinergic neurotransmission (Smith-White et al, 2002), but little is known about Y 2 receptor modulation of nonadrenergic, noncholinergic (NANC) neurotransmission. Y 2 receptors are not, however, always presynaptic, nor are Y 1 receptors exclusively postsynaptic, or postjunctional (Cox & Cuthbert, 1990;McAuley & Westfall, 1992;Mannon et al, 1999; for reviews see, Cox, 1998;Michel et al, 1998).…”