Short-chain fatty acids (SCFAs), including propionate, butyrate and acetate, are fermentation products of carbohydrates in the colon. We investigated the contractile effects of SCFAs on the rat distal colon. Mechanical activity of the circular muscle in strip preparations was recorded in vitro. Propionate and butyrate concentration-dependently (10 micromol L(-1)-10 mmol L(-1)) induced rapid, large amplitude phasic contractions (the first phase) followed by tonic contractions (the second phase). Acetate itself had no effect on muscle activity, although preincubation with acetate attenuated both phases of the propionate-induced response. The propionate-induced phasic contraction was attenuated by atropine, tetrodotoxin and the 5-HT4 receptor antagonist SB-204070. The propionate-induced tonic contraction was attenuated by the cyclo-oxygenase inhibitor piroxicam. Antagonists of 5-HT1A, 5-HT2A and 5-HT3 receptors had no effect on the responses. Propionate-induced responses were not observed in mucosa-free preparations. These results suggest that propionate acts on receptors in the mucosa causing the release of 5-HT from enterochromaffin cells. 5-HT acts through 5-HT4 receptors on the endings of intrinsic primary afferent neurones that in turn activate cholinergic motor neurones that contract the circular muscle. Propionate also causes tonic contraction, via prostaglandin release, in the rat distal colon.

tion in isolated segments and strips of rat colon via enteric reflex. It has also been reported that a high concentration (500 mM) of SCFAs infused into rat proximal colon reduces colonic motility and increases transit rate; SCFAs decrease the ratio of orally to aborally propagated activity to accelerate colonic transit, and this effect may be mediated through a neuroendocrine mechanism involving peptide YY (PYY) [8]. Fukumoto et al. [9] have recently reported that the administration of SCFAs (100 mM) into the proximal colon significantly increased colonic motility via vagovagal reflex involving the release of 5-HT from enterochromaffin cells (EC cells) in rats; the highamplitude contractions induced by SCFAs in the proximal colon migrated to the middle and distal colon, Japanese Journal of Physiology Vol. 54, No. 5, 2004 483 One of the most important events in the large intestinal lumen is the production of short-chain fatty acids (SCFAs) through the bacterial fermentation of carbohydrates in the cecum and proximal colon of monogastric mammals. SCFAs are the major anions of colonic contents, including mainly acetate, propionate, and butyrate in a molar ratio of 57:21:22 in the human right colon, respectively. The total concentration is usually ~130 Abstract: Short-chain fatty acids (SCFAs) produced by the bacterial fermentation of carbohydrates in the cecum and proximal colon are reported to modify colonic motility as a luminal factor. Besides the physical stimuli in the distal colon, SCFAs in the intestinal lumen also seem to affect colonic motility under physiological concentrations. This study therefore used fasted rats to investigate the effect of SCFAs on the spontaneous contractions of longitudinal muscle (LM) in rat distal colon, including mucosa in vitro. The frequency of spontaneous contractions of LM strips from the distal colon was 9.4 ± 0.5 contractions/20 min. The exogenous addition of >5 mM SCFAs decreased the frequency of spontaneous contractions of the LM to 6.1 ± 0.8 contractions/20 min. Among SCFAs, only acetate elicited this inhibitory response. TTX and the combination of hexamethonium and granisetron abolished SCFA-induced inhibitory response, suggesting that this inhibitory response is mediated via the ENS, including nicotinic and 5-HT 3 receptors. In conclusion, it is suggested that SCFAs in rat distal colon decrease the frequency of spontaneous contractions of the LM and that SCFAs may contribute to colonic motility, including the peristaltic reflex, by regulating the frequency of spontaneous contractions of the LM through the enteric nervous system (ENS).

Short-chain fatty acids, such as propionate and acetate, are produced by a bacterial fermentation of carbohydrates in the colonic lumen. We examined the effects of propionate on the frequency and mean amplitude of spontaneous giant contractions (GCs) in circular muscle strips of the rat distal colon with the mucosa attached. An addition of propionate increased the frequency of GCs for about 20 min (≥1 mm), but the mean amplitude was decreased (≥0.1 mm). The propionate-induced increase in the frequency of GCs was blocked by the muscarinic acetylcholine receptor antagonist, atropine. In contrast, the nicotinic receptor antagonist, hexamethonium, Chemicals in the intestinal lumen modulate the gut functions [1,2]. For example, HCl applied to the mucosa initiates the peristaltic reflex in the small intestine [3]. Bile salt [4,5] and nutrient [6,7] in the lumen are also known to modulate the motility of the small intestine. On the other hand, short-chain fatty acids (SCFAs), which are produced by a bacterial fermentation of carbohydrates, are contained in the colonic lumen and modulate motility of the colon. Intraluminal SCFAs stimulate muscle activity and accelerate colonic transit in the rat in vivo [8]. Among SCFAs, propionate or butyrate immediately evokes a contraction in rat distal colon muscle strips with the mucosa attached, but not without the mucosa [9,10]. These in vivo and in vitro studies suggest that SCFAs in the lumen stimulate colonic motility.

We have previously reported that there may be a relationship between bowel habits including functional constipation (FC) and irritable bowel syndrome and sleep health. However, our previous studies were based on only subjective parameters by self-reported questionnaire. The aim of this study is to investigate the relationship between bowel habits such as FC and sleep health using objective parameters. Sleep health was assessed by actigraphy measurement and bowel habits by fecal flora analysis. The FC and control subjects, whose bowel habits were defined at Rome II, were recruited from evaluated respondents in our previous study directed at middle-aged Japanese women, ten FC and ten control subjects participating in this study. Wake after sleep onset (WASO) and WASO (%) (WASO/total sleep time multiplied by 100) in FC subjects was significantly longer and greater than those in control subjects, respectively. Average activity during sleep in FC subjects was significantly higher than that in control subjects. FC had no effect on total sleep time. Bifidobacterium is broadly accepted to be useful intestinal bacteria for human health and one of the indices showing that the intestinal environment is in a desirable condition. Bifidobacterium counts per gram of wet feces and proportion in total bacterial cell counts in FC subjects were significantly lower than those in control subjects. In conclusion, these results suggest that corresponding to low Bifidobacterium counts and proportion, sleep in FC subjects may be worse than that in control subjects. There may be a relationship between bowel habits and sleep health. Bowel habits such as FC might be a risk factor for sleep disorders.

Antimicrobial peptides (AMPs) play an important role in innate immunity in human skin. It is known that AMPs mainly function in the stratum corneum. Therefore, AMP concentrations in the stratum corneum need to be precisely measured to clarify functional and physiological importance of AMPs in cutaneous defence. Tape stripping (TS) is a well-established method by which components in the stratum corneum can be collected. However, the usefulness of the TS method for measuring AMP concentration in human skin remains unclear. Therefore, we compared it with another popular method, skin rinsing, which had been established as a method for measuring AMP concentration in human skin. When investigated on healthy medial forearm using RNase 7, which is one of the typical AMPs, as an index, there was a significant positive correlation between RNase 7 concentrations measured by the TS method at adjacent forearm sites, demonstrating the reproducibility of the TS method. Next, a significant positive correlation was detected in RNase 7 concentrations measured using the TS and the skin rinsing method, indicating that the TS method is comparable to the skin rinsing method. Thus, we speculate that the TS method is useful for measuring AMP concentration in human skin.

Spontaneous contractions of the intestine are thought to play an important role in the gastrointestinal motility, including peristalsis. In the present study, we investigated mechanisms for regulation of the frequency of spontaneous contractions, using longitudinal muscle strips in rat distal colon. Atropine significantly decreased the frequency of spontaneous contractions, indicating that neuromuscular transmission via muscarinic receptors increases the frequency of spontaneous contractions. SB-204070, 5-HT 4 receptor antagonist also significantly decreased the frequency of spontaneous contractions, indicating that the activation of 5-HT 4 receptors also increases the frequency of spontaneous contractions. In conclusion, it is suggested that muscarinic and 5-HT 4 receptors participate in the regulation of the frequency of spontaneous contractions in the longitudinal muscle in rat distal colon, and that the frequency of spontaneous contraction is controlled by the enteric neurons.It is well known that the longitudinal and the circular muscles in the colon generate spontaneous contractions (1, 18), which are also termed giant contractions (GCs) by Gonzalez and Sarna (11). Recently, it has been reported that spontaneous contractions of the longitudinal muscle in mouse colon are of similar form, frequency and pharmacology to migrating motor complexes (MMCs) of colonic circular muscle (18). Because the mouse MMCs resemble peristaltic waves in their frequency and time course, and they migrate over half the length of the colon, MMCs are thought to be peristalsis in nature (17). Therefore, spontaneous contractions of the longitudinal muscle in the colon seem to play an important role in the gastrointestinal motility, including peristalsis, and to be a useful tool to investigate the regulation of colonic motor activity.There are number of studies to characterize spontaneous contractions (or GCs) in the colon (1, 6,11,15,18). However, mechanisms for the regulation of the frequency of spontaneous contractions in the colon are controversial, and not well understood. For example, it has been reported that the amplitude and frequency of GCs of circular muscle strips are significantly increased by tetrodotoxin (TTX), but unaffected by antagonists of 5-hydroxytryptamine (5-HT) receptors (11). On the other hand, the MMCs in mouse colon have been reported to be inhibited by alosetron, a 5-HT 3 receptor antagonist in vitro (6). Moreover, spontaneous contractions of the longitudinal muscle in mouse colon are abolished by TTX, hexamethonium and morphine (18). In contrast to the evidence that GCs or the MMC is neurogenic, there is also the evidence that spontaneous contractions are myogenic, so that spontaneous con-

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