Noradrenergic, noncholinergic inhibitory junction potentials in rat proximal colon: role of nitric oxide

Abstract

Using a single sucrose gap apparatus, experiments were performed to determine the involvement of nitric oxide (NO) in the generation of nonadrenergic, noncholinergic (NANC) inhibitory junction potentials in circular muscle of rat proximal colon. Inhibitors of NO synthase, N omega-nitro-L-arginine and its methyl ester, reduced the amplitude of the electrically evoked inhibitory junction potentials, without affecting membrane resting potential. Such an effect was stereospecific and it was prevented by L-arginine but not by D-arginine. Sodium nitroprusside induced a tetrodotoxin-resistant hyperpolarization, which was not affected by NO synthase inhibitors. Apamin reduced sodium nitroprusside induced hyperpolarization, as well as NANC inhibitory junction potentials, and alpha-chymotrypsin decreased the amplitude of electrical field stimulation evoked responses. Residual responses after NO synthase inhibitors or after alpha-chymotrypsin were further reduced by pretreatment with alpha-chymotrypsin or NO synthase inhibitors, respectively. These results suggest that, in rat colonic circular muscle, NO plays an important role in NANC inhibitory junction potential generation. However, another mechanism, peptidergic in nature, is also involved.

Neural modulation of the cyclic electrical and mechanical activity in the rat colonic circular muscle: putative role of ATP and NO

“…This co-localization suggests a putative role for both substances in NANC neurotransmission (Belai & Burnstock, 1994). In fact, a role for NO in the IJP has been proposed from results obtained with the sucrose-gap technique (Serio et al, 1995). However, NO is not fully responsible for the hyperpolarization induced by EFS since, in the presence of NO synthase (NOS) inhibitors, EFS does still cause a residual IJP.…”

“…However, NO is not fully responsible for the hyperpolarization induced by EFS since, in the presence of NO synthase (NOS) inhibitors, EFS does still cause a residual IJP. This may suggest a co-transmission in this tissue (Serio et al, 1995). In fact, in the rabbit stomach, NO, ATP and VIP have all been described as NANC mediators (Baccari et al, 1994).…”

“…First ATP and then VIP, were regarded as putative neurotransmitters in the gut (Burnstock et al, 1978;Manzini et al, 1986;Grider & Makhlouf, 1988). More recently, nitric oxide (NO) has been viewed as the main NANC inhibitory neurotransmitter in the gastrointestinal tract of many species (Boeckxstaens et al, 1991;Burleigh, 1992;Suthamnatpong et al, 1994;Serio et al, 1995;Takeuchi et al, 1996). However, it has become evident that IJPs may often show two phases, a fast and a slow hyperpolarization.…”

Involvement of nitric oxide and tachykinins in the effects induced by protease‐activated receptors in rat colon longitudinal muscle

“…Since NO is one of the main nonadrenergic noncholinergic inhibitory neurotransmitters to intestinal smooth muscle (Bennett, 1997), including rat colon (Serio et al, 1995;Mule`et al, 1999), we investigated its eventual involvement in the relaxation evoked by PAR-1 and PAR-2. Our data using L-NAME indicate that PAR-1 and PAR-2 activation induces NO production, responsible, at least in part, for the longitudinal muscle relaxation evoked by high concentrations of PARs.…”

Mechanisms underlying the nitric oxide inhibitory effects in mouse ileal longitudinal muscle

“…However, the intracellular mechanisms of relaxation induced by NO are not definitively clarified yet. In fact, apamin, an inhibitor of small-conductance Ca 2+ -dependent K + channels, is able to inhibit the NO effects in some preparations such as rat duodenum (Martins et al 1995) and colon (Serio et al 1995), guinea pig caecum (Shuttleworth et al 1999), and mouse duodenum (Serio et al 2003a). Moreover, association of Ca 2+ -activated K + channels with NO-mediated inhibition of gastrointestinal smooth muscle has been suggested.…”