Effect of galanin on isolated strips of smooth muscle from the gastrointestinal tract of chickens

The contractile effects of galanin on isolated longitudinal smooth muscle strips of pre-crop esophagus, proventriculus, duodenum, colon, and cecum of chickens were investigated. Application of galanin (5.0-100.0 nM) evoked strong contractions from the colon and cecum (hindgut), but evoked minimal responses from the pre-crop esophagus, proventriculus, and duodenum (foregut). Previous studies have demonstrated that the central administration of galanin stimulates food consumption in rats. Since galanin-like immunoreactivity is present in the chicken brain, we speculate that the central release of galanin may increase food intake and possibly be involved in a hypothalamic-colonic reflex modulating hindgut motility and generating a defecation. Thus, the results of this study demonstrate the presence of galanin receptors in the chicken gut and suggest a possible link with their functional presence in the hindgut to the chicken central nervous system.     

A qualitative and quantitative study on the enkephalinergic innervation of the pig gastrointestinal tract.

Enkephalins are involved in neural control of digestive functions such as motility, secretion, and absorption. To better understand their role in pigs, we analyzed the qualitative and quantitative distribution of enkephalin immunoreactivity (ENK-IR) in components of the intestinal wall from the esophagus to the anal sphincter. Immunohistochemical labelings were analyzed using conventional fluorescence and confocal microscopy. ENK-IR was compared with the synaptophysin immunoreactivity (SYN-IR). The results show that maximal ENK-IR levels in the entire digestive tract are reached in the myenteric plexuses and, to a lesser extent, in the external submucous plexus and the circular muscle layer. In the longitudinal muscle layer, ENK-IR was present in the esophagus, stomach, rectum, and anal sphincter, whereas it was absent from the duodenum to the distal colon. In the ENK-IR plexuses and muscle layers, more than 60% of the nerve fibers identified by SYN-IR expressed ENK-IR. No ENK-IR was observed in the internal submucous plexus and the mucosa; the latter was found to contain ENK-IR endocrine cells. These results strongly suggest that, in pigs, enkephalins play a major role in the regulatory mechanisms that underlie the neural control of digestive motility.     

Hormonal component of the postprandial motility response of the proximal stomach in dogs

The motility of a proximal gastric pouch, that has been extinsically denervated by autotransplantation, has been studied in 4 dogs. In the same time, the electrical activity of the duodenum was recorded with AgAgCl electrodes. Recordings were made in the fasting state and after oral administration of 250 ml NaCl 154 mM solutions containing 15 kcal/kg of either glucose, peptides or lipids, or 3 X 5 kcal/kg of a mixture of these three nutrients. The results showed, in the fasting state, that a cyclic activity took place in the denervated gastric pouch corresponding to the myoelectric complex observed at the same time in the duodenum. After feeding the dogs with any nutrient solution, we observed: 1) a decrease in pouch pressure; 2) an interruption of the cyclic activity in both the pouch and duodenum. A fasting motility resumed simultaneously in both the pouch and duodenum. These results indicate that hormonal agents are involved in the motility of the proximal stomach as well as in the postprandial interruption of the myoelectric complex.     

Failure of capsaicin-containing red pepper sauce suspension to induce esophageal motility response in patients with Barrett's esophagus.

The physiologic importance of afferent sensory pathways in the esophageal motor functions has been recently recognised. Capsaicin-sensitive sensory afferents were shown to play a role in the maintenance of mucosal integrity of the GI tract, and regulation of human esophageal motility. The aim of this study was to investigate the effect of topical application of capsaicin-containing red pepper sauce (Tabasco, 25%v/v, pH:7.0) suspension on the phasic activity of the human esophagus of healthy volunteers and patients with Barrett's esophagus. METHODS: The diagnosis of Barrett's esophagus was based on the findings of esophagoscopy and histology taken from the squamocolumnar junction of the esophagus. Esophageal motility was measured by perfusion manometry before and after application of red pepper sauce. RESULTS: Capsaicin containing red pepper sauce increases the motility response (LES tone, contraction amplitude, propagation velocity) of the human esophagus in healthy volunteers. This response failed in patients with Barrett's esophagus. CONCLUSION: Impaired esophageal sensory motor function may serve as one etiologic role in the development of Barrett's esophagus.     

Regulation of gastric emptying

Studies carried out in the years since William Beaumont's direct observations of gastric motility have provided increased understanding of the physiological roles of the stomach and of the mechanisms for the regulation of gastric motility. Tonic contractions of the proximal stomach are of primary importance for transfer of liquids from the stomach to the duodenum. Peristaltic contractions of the distal stomach are of primary importance for reducing the size of solid food particles and for transfer of solids to the duodenum. Because gastric emptying requires a net antral-duodenal pressure gradient, contractions of the duodenum also influence the rate of gastric emptying. Gastrointestinal hormones, including gastrin, cholecystokinin, secretin, somatostatin, and others, are released by contact of chyme with the intestinal mucosa, and affect contractions of the proximal stomach, distal stomach, and duodenum. Neural reflexes that arise from the stomach act through autonomic motor nerves to allow regulation by the central nervous system of gastric motility. gamma-Aminobutyric acid, opioids, and bombesin may serve as central neurochemical regulators of gastric motility.     

Failure of capsaicin-containing red pepper sauce suspension to induce esophageal motility response in patients with Barrett’s esophagus

The physiologic importance of afferent sensory pathways in the esophageal motor functions has been recently recognised. Capsaicin-sensitive sensory afferents were shown to play a role in the maintenance of mucosal integrity of the GI tract, and regulation of human esophageal motility. The aim of this study was to investigate the effect of topical application of capsaicin-containing red pepper sauce (Tabasco, 25%v/v, pH:7.0) suspension on the phasic activity of the human esophagus of healthy volunteers and patients with Barrett’s esophagus. Methods: The diagnosis of Barrett’s esophagus was based on the findings of esophagoscopy and histology taken from the squamocolumnar junction of the esophagus. Esophageal motility was measured by perfusion manometry before and after application of red pepper sauce. Results: Capsaicin containing red pepper sauce increases the motility response (LES tone, contraction amplitude, propagation velocity) of the human esophagus in healthy volunteers. This response failed in patients with Barrett’s esophagus. Conclusion: Impaired esophageal sensorymotor function may serve as one etiologic role in the development of Barrett’s esophagus.     

Evaluation of 100 Esophageal Motility Studies at a University Medical Center

100 esophageal motility studies on 88 consecutive patients referred to the University of California Medical Center were analyzed. Diagnoses of achalasia, diffuse spasm of the esophagus, scleroderma, hiatal hernia and other conditions were made from the motility tracings. The motility tests have been found to be most helpful in differentiating various disorders of swallowing and thoracic pain of unknown cause.     

Obestatin inhibits motor activity in the antrum and duodenum in the fed state of conscious rats

Obestatin is a novel peptide encoded by the ghrelin precursor gene; however, its effects on gastrointestinal motility remain controversial. Here we have examined the effects of obestatin on fed and fasted motor activities in the stomach and duodenum of freely moving conscious rats. We examined the effects of intravenous (IV) injection of obestatin on the percentage motor index (%MI) and phase III-like contractions in the antrum and duodenum. The brain mechanism mediating the action of obestatin on gastroduodenal motility and the involvement of vagal afferent pathway were also examined. Between 30 and 90 min after IV injection, obestatin decreased the %MI in the antrum and prolonged the time taken to return to fasted motility in the duodenum in fed rats given 3 g of chow after 18 h of fasting. Immunohistochemical analysis demonstrated that corticotropin-releasing factor- and urocortin-2-containing neurons in the paraventricular nucleus in the hypothalamus were activated by IV injection of obestatin. Intracerebroventricular injection of CRF type 1 and type 2 receptor antagonists prevented the effects of obestatin on gastroduodenal motility. Capsaicin treatment blocked the effects of obestatin on duodenal motility but not on antral motility. Obestatin failed to antagonize ghrelin-induced stimulation of gastroduodenal motility. These results suggest that, in the fed state, obestatin inhibits motor activity in the antrum and duodenum and that CRF type 1 and type 2 receptors in the brain might be involved in these effects of obestatin on gastroduodenal motility.     

Role of cholecystokinin in postprandial and vagally stimulated duodenal and gallbladder motility in dogs.

This study was designed to determine the role of cholecystokinin (CCK) in postprandial motility pattern of the duodenum and gallbladder (GB) in conscious dogs provided with chronic duodenal electrodes for recording of myoelectric activity and GB fistulas for measurement of intraluminal pressure and volume of GB and to calculate the GB motility index (MI) and GB emptying rate. During naturally occurring activity front (phase III MMC) in the duodenum there was significant increase in the MI of GB accompanied by about 20-30% reduction in the GB volume. These changes in duodenal and GB motility pattern could be duplicated by i.v. motilin. Feeding abolished the appearance of spontaneous activity front in the duodenum and greatly increased motility of GB while reducing its volume. Administration of CCK receptor antagonists in fed dogs failed to affect the motility changes induced by meal in the duodenum but abolished these of the GB. Vagal cholinergic stimulation with insulin, 2DG or urecholine caused similar effects to that induced by food i.e. increased duodenal spike activity, abolished phase III of the MMC, decreased GB volume and increased GB motility. Pretreatment with CCK antagonists did not affect significantly duodenal spike activity or GB motility but significantly increased the GB volume. Atropine 125 micrograms/kg) blocked almost completely spontaneous activity front in the duodenum and accompanying alterations in the motility and volume of GB. We conclude that CCK contributes to the MMC related alterations in the GB motor activity and is essential in cholinergic stimulation induced of the GB emptying but not in vagally induced duodenal and GB motility.     

Sensory innervation of the canine esophagus, stomach, and duodenum.

The sensory innervation of the postpharyngeal foregut was investigated by injecting the enzyme horseradish peroxidase (HRP) into the walls of the esophagus, stomach, or duodenum. The transported HRP was identified histochemically, labeled neurons in the spinal and vagal ganglia were counted, and the results were plotted using an SAS statistical program. The spinal sensory fields of each viscus were defined using three determinations: craniocaudal extent, principal innervation field, and peak innervation field. The data revealed that innervation fields are craniocaudally extensive, the sensory field of each viscus overlaps significantly with its neighbor, yet each viscus can be characterized by a field of peak innervation density. Craniocaudal innervation of the esophagus spans as many as 22-23 paired spinal ganglia (C1-L2). There are two peak innervation fields for the cervical (C2-C6 and T2-T4) and for the thoracic (T2-T4 and T8-T12) sectors of the esophagus. The sensory innervation of the stomach extends craniocaudally over as many as 25 paired spinal ganglia (C2-L5). The peak innervation field of the stomach spans a large area comprising the cranial, middle, and the immediately adjoining caudal thoracic ganglia (T2-T10). The duodenum is innervated craniocaudally by as many as 15 paired thoracolumbar ganglia (T2-L3). Peak innervation originates in the middle and caudal thoracic ganglia and cranial lumbar (T6-L1) ganglia. There is a recognizable viscerotopic organization in the sensory innervation of the postpharyngeal foregut; successively more caudal sectors of this region of the alimentary canal are supplied with sensory fibers from successively more caudal spinal dorsal root ganglia. Vagal afferent innervation of the esophagus, stomach, and duodenum is bilateral and originates predominantly, but not exclusively, from vast numbers of neurons in the nodose (distal) ganglia. The esophagus is innervated bilaterally and more abundantly by jugular (proximal) ganglia neurons than is either the stomach or duodenum. The physiological significance of the findings are discussed in relation to the phenomena of visceral pain and referred pain.     

Ghrelin, des-acyl ghrelin and obestatin on the gastrointestinal motility

Ghrelin, des-acyl ghrelin and obestatin are derived from a common prohormone, preproghrelin by posttranslational processing, originating from endocrine cells in the stomach. Ghrelin exerts stimulatory effects on the motility of antrum and duodenum in both fed and fasted state of animals. On the other hand, des-acyl ghrelin exerts inhibitory effects on the motility of antrum but not on the motility of duodenum in the fasted state of animals. Obestatin exerts inhibitory effects on the motility of antrum and duodenum in the fed state but not in the fasted state of animals. NPY Y2 and Y4 receptors in the brain may mediate the action of ghrelin, CRF type 2 receptor in the brain may mediate the action of des-acyl ghrelin, whereas CRF type 1 and type 2 receptors in the brain may mediate the action of obestatin.     

Effects of central and peripheral urocortin on fed and fasted gastroduodenal motor activity in conscious rats

Since few previous studies have examined the effects of urocortin on physiological fed and fasted gastrointestinal motility, we administered urocortin intracerebroventricularly (icv) or intravenously (iv) in freely moving conscious rats and examined the changes in antral and duodenal motility. Icv and iv injection of urocortin disrupted fasted motor patterns of gastroduodenal motility, which were replaced by fed-like motor patterns. When urocortin was given icv and iv in the fed state, the motor activity remained like the fed patterns but % motor index (%MI) was decreased in the antrum and increased in the duodenum. Increase in the %MI in the duodenum induced by urocortin was shown as a nonpropagated event, since the transit of nonnutrient contents in the duodenum was decreased by icv and iv injection of urocortin. Changes in the gastroduodenal motility induced by icv injection of urocortin were abolished in animals with truncal vagotomy but not altered in animals with mechanical sympathectomy, suggesting that the vagal pathway may mediate the central action of urocortin. Neither urocortin antiserum nor alpha-helical CRF-(9-41) affected fed and fasted gastroduodenal motility, suggesting that endogenous urocortin is not involved in regulation of basal gastroduodenal motility.     

东方蝾螈消化道5-羟色胺免疫活性细胞的分布与形态学观察,前插2

采用ABC免疫组织化学方法对东方蝾螈Cynops orientalis消化道内5-羟色胺免疫活性内分泌细胞的分布及形态进行观察.结果显示,5-羟色胺(5-HT)细胞从食管到直肠各段均有分布,其中十二指肠的分布密度最高,空肠次之,幽门和直肠部最低.5-HT细胞形态多样呈圆形、锥体形和梭形等,根据其形态认为东方蝾螈消化道5-HT免疫活性细胞具有内分泌、外分泌两种功能.     

A gastrointestinal function bioassay evaluation of the mycotoxin,T-2 trichothecene

The Fusarium-produced mycotoxin T-2 trichothecene toxin was administered to two groups of young CD-1 mice to test the effects on three parameters of intestinal motility. The criteria selected included composite motility (cm²/min), peak amplitude (mm) and contraction frequency (recorded peaks/min). T-2 treated mice showed an increase in composite motility in response to low dosage (0·085 mg/kg), and at the higher dosage (0·250 mg/kg) a decreased motility. In the lowest treatment group there was a mean decrease of 39·54% in contraction amplitude while contraction frequency increased by 24·84%. The motility measurements were obtained by perfusing 2 cm sections of small intestine, including the entire duodenum excised from mice pre-treated with mycotoxin. Contractions were recorded with a physiograph and the composite motility measurements were taken using a computer program to determine the area of the data curves. T-2 toxin caused an alteration in the amplitude and frequency of motility measurements, but no overall concentration-related changes were noted. T-2 toxin causes measurable responses in the duodenum which may be one of the sites-of-action for this mycotoxin.     

Neural and hormonal control of Brunner's gland secretion

For many years it has been speculated that the physiological function of Brunner's glands was to secrete mucus to protect the proximal duodenum from the corrosive effects of acidified gastric juice. However the control of Brunner's gland secretion remains an enigma. Some evidence exists which indicates both cholinergic and adrenergic innervation of these glands, but current consensus weighs heavily in favor of a hormonal stimulus for glandular secretion. This is based in part on evidence obtained from denervated Brunner's gland pouches following a feeding stimulus. A number of hormones and hormone-like substances have been investigated as possible mediators in this secretory response, however, no specificity was ever demonstrated. The inability to pinpoint a given substance as a common mediator can be attributed to the fact that most active agents employed also affect duodenal motility. We present evidence that Brunner's gland secretion can be observed to be a diphasic response. The initial, transient response is always observed in the presence of increased duodenal motility. The sustained response does not require duodenal motility and is probably hormonally mediated.     

Influence of methochlopramide on the motor function of the esophagus and the cardial sphincter]

In acute experiments on cats and in chronic experiments on dogs the contractile activity of the esophagus and the cardiac sphincter was recorded with a ballon pulled from the stomach to the esophagus connected to a catheter. The intravenous injection of Metoclopramide in doses of 0.5--0.6 mg/kg to cats and subcutaneous injection of Metoclopramide in doses of 0.1--0.15 mg/kg to dogs elevated the pressure in the cardiac sphincter significantly increased the motility of the distal esophagus and stimulated the esophago-gastric inhibitory reflex. These effects persisted for 2.5--3 hrs; they were phasic in nature and were preserved after vagotomy in dogs. A conclusion was drawn that Metoclopramide could be useful in pathology of the distal esophagus, including the cardiac sphincter.     

Localization of xenopsin and xenopsin precursor fragment immunoreactivities in the skin and gastrointestinal tract of Xenopus laevis

Summary Xenopsin (Xp) and xenopsin precursor fragment (XPF) are bioactive peptides derived from a single precursor molecule; both were isolated previously from extracts of Xenopus laevis skin. The present immunohistochemical study was undertaken to determine the specific cellular localization of these two peptides in the skin and also in the gastrointestinal tract of adult Xenopus. We report here that Xp-like and XPF-like immuno-reactivities co-exist in the granular glands of the skin and specific granular cells in the lower esophagus and stomach. However, only Xp-like immunoreactivity, not XPF-like immunoreactivity, was detected in tall, thin cells of the duodenum and in club-shaped cells of the large intestine. The immunochemical co-localization of the two peptides in specific cells of the skin, lower esophagus and stomach suggests that the same gene is expressed in each of these cells, and that the precursor molecule undergoes similar post-translational processing. In contrast, the observation that certain cells of the duodenum and large intestine display only one peptide immunoreactivity suggests an alternative phenomenon, possibly involving selective peptide accumulation or expression of a different gene.     

Bile salts induce or blunt cell proliferation in Barrett's esophagus in an acid-dependent fashion

Barrett's esophagus (BE) results from acid and bile reflux and predisposes to cancer. We investigated the effect of bile salts, with or without acid, on cell proliferation in BE and assessed mechanism(s) involved. To mimic physiological conditions, biopsies of esophagus, BE, and duodenum were exposed to a bile salt mixture, either continuously or as a 1-h pulse, and were compared with control media without bile salts (pH 7.4) for < or =24 h. Similar experiments were also performed with acidified media (pH 3.5) combined with the bile salt mixture as a 1-h pulse. Cell proliferation was assessed by a [(3)H]thymidine incorporation assay with or without bisindolylmaleimide (BIM), a selective protein kinase C inhibitor. Bile salt pulses enhanced cell proliferation in BE without affecting cell proliferation in esophageal or duodenal epithelia. In the presence of BIM, there was complete obliteration of the bile salt-induced BE hyperproliferation. In contrast, 1-h pulses of bile salts in combination with acid significantly inhibited proliferation in BE but had no effect on esophagus or duodenum. We conclude that in BE explants, brief exposure to bile salts, in the absence of acid, increases proliferation, whereas exposure to a combination of bile salts and acid together inhibits proliferation.     

北方狭口蛙消化道5一羟色胺细胞的免疫组织化学定位

目的探讨北方狭口蛙（Kaloula borealis）消化道5-羟色胺细胞的分布密度规律和形态学特点。方法免疫组织化学SABC法鉴别和定位雌雄各6只北方狭口蛙食管、贲门、胃体、幽门、十二指肠、空肠、回肠和直肠的5-羟色胺细胞。结果5-羟色胺细胞的分布密度高峰位于胃幽门部,胃体和十二指肠其次,贲门最低。开放型和闭合型细胞的比值从食管至直肠呈”V”形分布,胃幽门部为比值的最低点。食管、贲门和肠道各段的5一羟色胺细胞以开放型细胞为主,胃体开放型和闭合型细胞的数量几近相等,胃幽门部以闭合型细胞为主。结论北方狭口蛙消化道5-羟色胺细胞的分布型和形态学特点与其他两栖动物既有相同点,也有自身的独特性,这可能与其食性和善于穴居掘土的生活方式有关。