We studied whether physiological concentration of short-chain fatty acids (SCFAs) affects colonic transit and colonic motility in conscious rats. Intraluminal administration of SCFAs (100-200 mM) into the proximal colon significantly accelerated colonic transit. The stimulatory effect of SCFAs on colonic transit was abolished by perivagal capsaicin treatment, atropine, hexamethonium, and vagotomy, but not by guanethidine. The stimulatory effect of SCFAs on colonic transit was also abolished by intraluminal pretreatment with lidocaine and a 5-hydroxytryptamine (HT)(3) receptor antagonist. Intraluminal administration of SCFAs provoked contractions at the proximal colon, which migrated to the mid- and distal colon. SCFAs caused a significant increase in the luminal concentration of 5-HT of the vascularly isolated and luminally perfused rat colon ex vivo. It is suggested that the release of 5-HT from enterochromaffin cells in response to SCFAs stimulates 5-HT(3) receptors located on the vagal sensory fibers. The sensory information is transferred to the vagal efferent and stimulates the release of acetylcholine from the colonic myenteric plexus, resulting in muscle contraction.

It has been demonstrated that nitric oxide (NO) is a major inhibitory nonadrenergic, noncholinergic (NANC) neurotransmitter in the gastrointestinal (GI) tract. NO released in response to nerve stimulation of the myenteric plexus causes relaxation of the smooth muscle. NO is synthesized by the activation of neuronal NO synthase (nNOS) in the myenteric plexus. Released NO plays an important physiological role in various parts of the GI tract. NO regulates the muscle tone of the sphincter in the lower esophagus, pylorus, sphincter of Oddi, and anus. NO also regulates the accommodation reflex of the fundus and the peristaltic reflex of the intestine. Previous studies have shown that NOS inhibitors delay gastric emptying and colonic transit. The reduction of nNOS expression, associated with impaired local production of NO, may be responsible for motility disorders in the GI tract. There is accumulated evidence that dysfunction of NO neurons in the myenteric plexus may cause various GI diseases. These reports are reviewed and possible mechanisms of altered nNOS expression are discussed in this article. In particular, impaired nNOS synthesis of the myenteric plexus seems to be an important contributing factor to the pathogenesis of achalasia, diabetic gastroparesis, infantile hypertrophic pyloric stenosis, Hirschsprung's disease, and Chagas' disease. Reduced NO release and/or nNOS expression are suspicious in a subset of patients with functional dyspepsia. Although the etiology of intestinal pseudo-obstruction remains unknown, it is conceivable that extrinsic denervation may upregulate nNOS expression, resulting in enhanced muscular relaxation and disturbed peristalsis. An animal model of colitis showed impaired nNOS expression in the colonic myenteric plexus. Antecedent infection may be associated with the impaired NO pathways observed in functional dyspepsia, colitis, and Chagas' disease.

Nine patients with cystic hygroma were treated with a new sclerosing therapy consisting of intracystic injection of OK-432 (group A Streptococcus pyogenes of human origin). Favourable results including complete regression in eight patients and marked regression in one were observed within 2-3 months without serious side-effects except for fever of 2-3 days' duration and local inflammatory reaction lasting for 3-4 days. Local inflammatory reaction did not cause any damage to the overlying skin and did not lead to scar formation.

Accumulation of continuous life stress (chronic stress) often causes gastric symptoms. Although central oxytocin has antistress effects, the role of central oxytocin in stress-induced gastric dysmotility remains unknown. Solid gastric emptying was measured in rats receiving acute restraint stress, 5 consecutive days of repeated restraint stress (chronic homotypic stress), and 7 consecutive days of varying types of stress (chronic heterotypic stress). Oxytocin and oxytocin receptor antagonist were administered intracerebroventricularly (icv). Expression of corticotropin-releasing factor (CRF) mRNA and oxytocin mRNA in the paraventricular nucleus (PVN) of the hypothalamus was evaluated by real-time RT-PCR. The changes of oxytocinergic neurons in the PVN were evaluated by immunohistochemistry. Acute stress delayed gastric emptying, and the delayed gastric emptying was completely restored after 5 consecutive days of chronic homotypic stress. In contrast, delayed gastric emptying persisted following chronic heterotypic stress. The restored gastric emptying following chronic homotypic stress was antagonized by icv injection of an oxytocin antagonist. Icv injection of oxytocin restored delayed gastric emptying induced by chronic heterotypic stress. CRF mRNA expression, which was significantly increased in response to acute stress and chronic heterotypic stress, returned to the basal levels following chronic homotypic stress. In contrast, oxytocin mRNA expression was significantly increased following chronic homotypic stress. The number of oxytocin-immunoreactive cells was increased following chronic homotypic stress at the magnocellular part of the PVN. Icv injection of oxytocin reduced CRF mRNA expression induced by acute stress and chronic heterotypic stress. It is suggested that the adaptation mechanism to chronic stress may involve the upregulation of oxytocin expression in the hypothalamus, which in turn attenuates CRF expression.

We investigated the vagal pathways mediating the gastric accommodation reflex in the rat stomach. Gastric distension (6 ml) evoked an increase of 9.0 ± 1.0 cm H2O of intragastric pressure in vivo. Pretreatment with tetrodotoxin (TTX) caused a significant pressure increase by gastric distension, reaching 17.0 ± 1.7 cm H2O, suggesting mediation by neural pathways. The pressure increase evoked by gastric distension was significantly enhanced in vivo by acute truncal vagotomy (TV), hexamethonium (C6), and NG‐nitro‐L‐arginine methyl ester (l‐NAME), but not by vasoactive intestinal polypeptide (VIP) antiserum, guanethidine, or splanchnicotomy. Gastric distension (6 ml) evoked a much larger intragastric pressure in the denervated, vascularly isolated, perfused rat stomach in vitro. Intra‐arterial application of TTX and l‐NAME did not cause further pressure increases evoked by gastric distension. The pressure increase evoked by gastric distension remained high 2 weeks after TV in vivo. However, the accommodation reflex was fully restored 4 weeks after TV in vivo. This reflex was antagonized by TTX, C6 and l‐NAME, but not by VIP antiserum, guanethidine and splanchnicotomy. Similar to in vivo studies, gastric distension caused a smaller increase in intragastric pressure in response to gastric distension in the denervated, vascularly isolated, perfused stomach obtained from rats 4 weeks after vagotomies in vitro. The pressure increase evoked by gastric distension was significantly enhanced by l‐NAME, hexamethonium and TTX. It is suggested that the vago‐vagal reflex plays an important role in mediating the accommodation reflex. This involves a vagal efferent pathway that uses nitric oxide as a final neurotransmitter mediating gastric relaxation in intact rats. It is also suggested that the adaptive mechanism mediating the accommodation reflex following vagotomy occurs in the gastric myenteric plexus.

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Central corticotropin-releasing factor (CRF) delays gastric emptying through the autonomic nervous system. CRF plays an important role in mediating delayed gastric emptying induced by stress. However, it is not clear whether a sympathetic or parasympathetic pathway is involved in the mechanism of central CRF-induced inhibition of solid gastric emptying. The purpose of this study was to investigate whether 1) CRF inhibits solid gastric emptying via a peripheral sympathetic pathway and 2) stress-induced inhibition of solid gastric emptying is mediated via a central CRF and peripheral sympathetic pathways. Using male Sprague-Dawley rats, CRF was injected intracisternally with or without various adrenergic-blocking agents. To investigate whether central CRF-induced inhibition of solid gastric emptying is mediated via a peripheral sympathetic pathway, rats underwent celiac ganglionectomy 1 wk before the gastric emptying study. After solid meal ingestion (90 min), gastric emptying was calculated. To investigate the role of endogenous CRF in stress-induced delayed gastric emptying, a CRF type2 receptor antagonist, astressin2-B, was intracisternally administered. Rats were subjected to a restraint stress immediately after the feeding. Intracisternal injection of CRF (0.1-1.0 microg) dose-dependently inhibited solid gastric emptying. The inhibitory effect of CRF on solid gastric emptying was significantly blocked by guanethidine, propranolol, and celiac ganglionectomy but not by phentolamine. Restraint stress significantly delayed solid gastric emptying, which was improved by astressin2-B, guanethidine, and celiac ganglionectomy. Our research suggests that restraint stress inhibits solid gastric emptying via a central CRF type2 receptor and peripheral sympathetic neural pathway in rats.