Modulation by NO of acetylcholine release in the ileum of wild-type and NOS gene knockout mice

Abstract

Mang, Christian F., Sebastian Truempler, Doris Erbelding, and Heinz Kilbinger. Modulation by NO of acetylcholine release in the ileum of wild-type and NOS gene knockout mice. Am J Physiol Gastrointest Liver Physiol 283: G1132-G1138, 2002 10.1152/ajpgi.00192.2002 inhibits the release of acetylcholine and cholinergic contractions in the small intestine of several species, but no information is available about the mouse ileum. This study examines the effects of NO on the electrically evoked release of 3 H]acetylcholine release and cholinergic contractions in preparations from wild-type mice and from eNOS knockout mice. Effects of L-NNA were specifically antagonized by L-arginine. In contrast, L-NNA and ODQ did not modify the release and contractions in preparations from nNOS knockout mice. The NO donor S-nitroso-N-acetyl-DLpenicillamine inhibited the electrically evoked release of [ 3 H]acetylcholine and longitudinal muscle contractions in a quantitatively similar manner in wild-type preparations as well as in nNOS and eNOS knockout preparations. We conclude that endogenous NO released by electrical field stimulation tonically inhibits the release of acetylcholine. Furthermore, data suggest that nNOS and not eNOS is the enzymatic source of NO-mediating inhibition of cholinergic neurotransmission in mouse ileum. neuronal nitric oxide synthase knockout mice; endothelial nitric oxide synthase knockout mice; cholinergic neurotransmission NITRIC OXIDE (NO) is a nonadrenergic, noncholinergic neurotransmitter that causes inhibition of intestinal motility (for review, see Ref. 24). The relaxant action of NO is probably not confined to its direct action on smooth muscle, because NO decreases intestinal motility also indirectly by inhibiting the release of the functionally most prominent excitatory enteric neurotransmitters acetylcholine and substance P. For example, exogenous NO (31) and NO donors (5) inhibit the electrically evoked release of acetylcholine from guinea pig ileum. Vice versa, NO synthase (NOS) inhibitors enhance the evoked release of acetylcholine from the ileum of guinea pig (10,20) and dog (7) as well as the electrically evoked cholinergic and tachykininergic contractions of guinea pig ileum (6,32). This suggests that endogenous NO, released by field stimulation, decreases the evoked release of acetylcholine from enteric neurones. There are, however, tissue and species differences in the neuromodulatory effect of NO: NO or NOS inhibitors do not modify the electrically evoked acetylcholine release from the colon of guinea pig and dog (22,29) and from stomach preparations of man (13

Inhibitory effects of daidzein on intestinal motility in normal and high contractile states

“…The α-adrenergic antagonist phentolamine and the β-adrenergic antagonist propranolol partially blocked the inhibitory effects induced by daidzein, respectively, and this evidence implicates that the inhibitory effect of daidzein on intestinal motility is correlated with the stimulation of adrenergic α, and β-adrenergic receptors. Inhibition of intestinal motility is also mediated by NO which is a nonadrenergic, noncholinergic neurotransmitter, producing its effect by directly acting on smooth muscle and by indirectly inhibiting acetylcholine and substance P releasing (Mang et al, 2002;Li et al, 2002). Our study showed that NO synthase inhibitor L-NNA did not affect the inhibitory effects produced by daidzein significantly; implicating that NO nonadrenergic, noncholinergic inhibitory pathways were not involved in daidzein-induced inhibitory effects.…”

Transient expression of NOS-II during development of the murine enteric nervous system

“…From studies in animals and in humans, it has been shown that NO may play an important role in the process of development and maturation (Belai & Burnstock 2000). However, there are other studies, specifically of the mouse, that have identified NOS-I as the source of NO in inhibitory neurotransmission (Mashimo et al 1996, Kim et al 1999, Mang et al 2002. However, for myenteric neurons and the interstitial cells of Cajal in the adult mouse colon, it has been reported that all neurons co-express NOS-III and NOS-II, while about 50% of them also co-express NOS-I (Vannucchi et al 2002).…”

Decrease of guanylyl cyclase β1 subunit and nitric oxide (NO)-induced relaxation in mouse rectum with colitis and its reproduction on long-term NO treatment

“…Usually, the whole ringpreparations (including mucosal layers, circular muscles, and neuronal plexus) were suspended in the longitudinal direction under a 1-gf load in a 5-mL organ bath containing the buffer. In some experiments, mucosal layers and circular muscles were mechanically removed with a damp wisp of cotton as described (Mang et al 2002), and the responses in the longitudinal muscle preparations were examined. The bath was maintained at 37°C and continuously bubbled with a mixture of 95% O 2 and 5% CO 2 .…”