Contractions Of Small Intestine Research Articles

Octreotide acetate induces fasting small bowel motility in patients with dumping syndrome

The long acting somatostatin analogue octreotide acetate has been effective in the treatment of early dumping syndrome. We hypothesized that this may be related to its effects on inhibiting gastric emptying and delaying intestinal transit. To study the effects of octreotide acetate on intestinal motility in patients we carried out a randomized, double-blinded study using a subcutaneous injection of either octreotide acetate (100 μg) or placebo given 20 min prior to ingestion of a high carbohydrate “dumping” meal in six patients with known severe dumping syndrome. Prior to each study a multilumen polyethylene tube was inserted into the efferent limb to study small intestinal contractions using low compliance pneumo-hydraulic water-perfused manometry. Octreotide acetate prevented dumping symptoms in all six patients and induced the appearance of migrating myoelectric complexes (MMC) characteristic of interdigestive motility. After ingestion of the dumping meal the postprandial “fed” motility pattern lasted for 141 ± 9 min while after octreotide acetate the fed motility lasted for 29 ± 5 min ( P < 0.03). The vigor of the fed motility pattern as measured by the motility index (MI = log e{sum of amplitudes × No. of contractions + 1}) was lower after octreotide acetate than after placebo (15.1 ± 0.1 vs 13.4 ± 0.2, P < 0.03). The induction of fasting MMC motility pattern and reduction in the duration and vigor of fed motility may explain the symptomatic relief these patients obtained with octreotide acetate. It is not known whether the induction of the MMC is a direct effect of octreotide acetate or secondary to the concomitant inhibition of peptide release (neurotensin, insulin, glucagon, pancreatic polypeptide) that has been demonstrated in earlier studies.

The effect of age on the rhythmic contractions of the rat small intestine

In vivo and in vitro rates of intestinal rhythmic contractions were measured in the same rats varying in age from very young to the senescent. Two rat strains, three small intestine locations, and six ages were compared. Contraction rates determined in vivo and in vitro were similar. Rhythmic contractions at all ages were fasted in the duodenum, slower in the jejunum, and slowest in the ileum. Contractions at 10 days of age were significantly slower than at all other ages; otherwise no systematic age-associated difference in contractions was demonstrated in either strain. Several factors were suggested as possibly influencing the developmental aspects of contraction rate and, therefore, their potential involvement in the early post natal period was suggested. It appears that old age does not influence the rate at which rhythmic contractions occur in the small intestine of the rat, and very possibly, these results are applicable to other species including humans.

Evidence that neuromedin U may regulate gut motility in reptiles but not in mammals

Neuromedin U-8 induced a monophasic and concentration-dependent contraction of intact small intestine from the turtle, Pseudemys scripta, whereas the peptide had no effect upon the motility of rat and guinea pig gut. The maximum response produced by neuromedin U-8 was 56% of that produced by acetylcholine and 62% of that produced by potassium chloride. The potency and maximum response to neuromedin U-8 were unaffected by tetrodotoxin and atropine. The data suggest that neuromedin U may play a role in regulation of gut motility in lower vertebrates but not in mammals.

Studies on attenuation of rotavirus

The development of rotavirus vaccines against acute gastroenteritis for human infants has been accorded a very high priority. Several vaccine candidates all of which are live cultivated strains of animal origin have been tested in humans. However the nature of attenuation of these viruses for humans is unknown. In this study we have attenuated a pig rotavirus by 15 sequential passages in cell culture after which the virus no longer causes diarrhoea in piglets. The pathogenesis of infection of the attenuated rotavirus strain (AT/76 P15) in gnotobiotic piglets was compared with that of the virulent parent strain (AT/76). The pattern of virus replication in the small intestine was judged by histology, disaccharidase assay, immunoperoxidase labelling of gut sections using group A specific rotavirus antibody, and rotavirus antigen assay of gut contents. The parent strain caused variable but extensive infection that resulted in the complete destruction of mature small intestinal enterocytes and villous contraction within 3 days. Membrane bound digestive enzymes were lost, and profound watery diarrhoea and dehydration resulted in causing piglets to become moribund. In contrast attenuated virus appeared to propagate at a much slower pace. Fewer infected epithelial cells were detected at any one time. Destruction of enterocytes was never extensive enough to cause marked mucosal changes in histology. Membrane bound digestive enzymes remained near normal levels and there was little or no diarrhoea. Virus replication ceased after 6 days. It is concluded that attenuation of the porcine rotavirus strain studied was associated with its decreased ability to propagate in enterocytes after adaption to culture.

Computer analysis of orally propagated contractions in canine small intestine after Billroth-II gastrectomy.

The aims of the study were to characterize an unusual motor pattern with orally propagated intestinal contractions occurring after subtotal gastrectomy and to clarify if orally propagated contractions also occur during the normal fasted and fed motor pattern in intact dogs. Jejunal motility was recorded with multiple closely spaced extraluminal transducers. Contractile patterns were analyzed by a special computerized method. Following a Billroth-II gastrectomy without additional vagotomy, the migrating motor complex was often disrupted and replaced by a motor pattern that consisted of contractions propagating aborally and retrograde. The propagation velocity was significantly faster compared with that of phase III contraction waves. In intact dogs, both the fasted and fed motor patterns showed a negligible number of orally propagated contractions. These results show that it is possible to differentiate between aborally and orally propagating contractions by a computerized method. Orally propagated contractions occur frequently after subtotal gastrectomy with gastroenterostomy but are an uncommon feature in intact dogs.

Involvement of substance P neurons in contractions of canine small intestine produced by mesenteric nerve stimulation

Pathways for contractions of in vivo canine small intestine produced by mesenteric nerve stimulation (MNS) were studied. In intact and chronically sympathectomized dogs, contractions of jejunal and ileal segments were largely reduced by intra-arterial infusion of capsaicin (10–100 μM, 0.07 ml/min), substance P (SP) antagonist, ( d-Pro 4, d-Trp 7.9) SP (4–11) (100 μM, 0.14 ml/min), hexamethonium (100–1000 μM, 0.07 ml/min) or atropine (100 μM, 0.07 ml/min). In chronically vagotomized dogs, capsaicin, SP-antagonist or atropine significantly reduced MNS-induced contractions, but hexamethonium did not. In dogs in which the coeliac and superior mesenteric ganglia had previously been removed, MNS caused no response although intra-arterial injection of 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP, 0.1 μmol) caused marked contractions. It may therefore be suggested that extrinsic SP neurons probably originating in spinal ganglia and intrinsic SP neurons receiving input from vagal preganglionic cholinergic neurons are involved in the excitatory pathways to MNS-induced contractions and that activation of these neurons excites myenteric cholinergic neurons, thereby causing contractions of the small intestine.

Functional localization of specific receptors mediating gastrointestinal motor correlates of vomiting

The gastrointestinal motor correlates of vomiting consist of two contractile events, 1) a giant retrogradely propagated contraction of the upper small intestine, the retrograde giant contraction (RGC) and 2) a series of post-RGC phasic contractions that occur primarily in the lower small intestine. The effects of cholinergic, dopaminergic, serotonergic, and opioid receptor antagonists and an opioid receptor agonist on vomiting and its gastrointestinal motor correlates initiated by apomorphine (APO), CuSO4, or cholecystokinin octapeptide (CCK-8) were determined in awake dogs. Atropine blocked the retrograde giant contraction only, and hexamethonium blocked all jejunoileal motor responses activated by APO, CuSO4, or CCK-8. Domperidone blocked all effects of APO only, whereas haloperidol, methysergide, 1-(1-naphthyl) piperazine, and fentanyl blocked or inhibited responses to both APO and CuSO4. None of the dopaminergic, serotonergic, or opioid receptor antagonists or the opioid receptor agonist affected the gastrointestinal motor responses to CCK-8. Cinanserin or Sch 23390 had no effect on any of the responses activated by APO, CuSO4, or CCK-8. These results suggested that D2 dopaminergic and 5-HT2 serotonergic receptors of the emetic central pattern generator mediate vomiting and its gastrointestinal motor correlates, whereas opioid receptors may mediate tonic inhibition of these responses. In addition, peripheral muscarinic or nicotinic cholinergic receptors but not peripheral 5-HT2, dopaminergic, or opioid receptors mediate the gastrointestinal motor correlates of vomiting.

Actions of galanin fragments on rat, guinea-pig, and canine intestinal motility

The 1-20 fragment of synthetic porcine galanin, prepared by tryptic digestion of the intact molecule, was equipotent to synthetic porcine galanin 1-29 in the smooth muscle actions of exciting the rat jejunal longitudinal muscle in vitro and inhibiting circular muscle contractions of the canine small intestine in vitro and in vivo, but was less potent in inhibiting nerve-stimulated contractions of the guinea-pig taenia coli. Fragment 21-29 was effective at high doses only in the canine ileum. Activity of galanin 1-11 was greatly reduced in the dog in vivo. These results may reflect species or cell type differences.

Activation of endogenous excitatory opiate pathways in canine small intestine by field stimulation and motilin.

Field stimulation of intrinsic nerves (40 V, 0.5 ms, 1-5 pps for 3-10 min) or intraarterial administration of motilin (10(-11)-10(-8 mol) caused contractions of the canine small intestine that were partially resistant to atropine and abolished by tetrodotoxin. Naloxone (10 micrograms ia or 200 micrograms/kg iv) in selective doses (10(-10)-10(-9) mol) that left responses to intra-arterial acetylcholine unaffected reduced responses to field stimulation or motilin in the ileum in the absence of atropine or residual responses in the presence of atropine. Results in the jejunum were similar except that selective doses of naloxone (10 micrograms ia or 200 micrograms/kg iv) increased the sensitivity to motilin in the absence of atropine. Higher doses of naloxone decreased these responses. In common with naloxone, tachyphylaxis to methionine-enkephalin (Met-Enk) reduced the responses to field stimulation or motilin before or after atropine but did not affect the responses to acetylcholine before or the responses to field stimulation of muscle after atropine. These findings are consistent with the hypothesis that Met-Enk may be a noncholinergic, excitatory transmitter released by field stimulation of nerves or intra-arterial motilin in the canine intestine.

μ, but not κ, opioid agonists induce contractions of the canine small intestine ex vivo

The proposed κ opioid receptor agonists ethylketocyclazocine (EK), nalorphine, bremazocine and U-50,488H were evaluated for their ability to produce contractions of isolated, vascularly perfused canine small intestinal segments. Responses to these agonists were compared to those of morphine and phenazocine, a μ benzomorphan. Morphine (0.04–25 μg) and phenazocine (0.01–3.0 μg) both produced naloxone-reversible contractions, suggesting that the responses were mediated largely by μ opioid receptors. In contrast, the proposed κ agonists were ineffective in producing intestinal stimulation, with only EK (1–100 μg) showing minimal but significant activity at very high doses. We suggest that the effects of EK may be mediated through μ opioid receptors and that κ receptors appear not to be involved in the contractile response of the dog small intestine to opioids.

μ and δ, but not κ, opioid agonists induce contractions of the canine small intestine in vivo

Extraluminal strain gage transducers were sutured along the transverse axis of the duodenum in order to monitor circular muscle contractile activity in the pentobarbital anesthetized dog. Administration by intravenous bolus of a variety of μ- and δ-directed opioid ligands resulted in a dose-dependent increase in duodenal contractile activity. In contrast, all κ-directed ligands were devoid of stimulatory activity. Naloxone reversed the effects of normorphine and [Met 5]enkephalin but was 20 times more effective against normorphine than [Met 5]enkephalin. Based on the inactivity of all κ ligands examined and the differential potency of naloxone against [Met 5]enkephalin and normorphine, we suggest that this model may be useful in the classification of opioid ligands as to their receptor selectivity in vivo. Further, these data indicate that the stimulation of duodenal contractile activity is not mediated by enteric κ receptors.

Localization of Isoproterenol-Induced Contractions of Canine Small Intestine

Localization of Isoproterenol-Induced Contractions of Canine Small Intestine

Isoproterenol induced contractions of the canine small intestine: The localization of the effect by drugs

Isoproterenol induced contractions of the canine small intestine: The localization of the effect by drugs

New type of nerve-mediated cholinergic contractions of the guinea-pig small intestine and its selective blockade by capsaicin.

A hypothesis is put forward that nerve fibres characterized by their specific sensitivity to capsaicin, presumably originating from sensory neurons excite cholinergic neurons of the myenteric plexus.

Effects of transection on the intestinal slow-wave frequency gradient.

Effects of transection on the intestinal slow-wave frequency gradient.

Effect of cholecystokinin on small intestine.

AbstractThe effect of highly purified cholecystokinin on gall‐bladder and intestine was investigated in vivo and in vitro. The following results were obtained: The contraction of small intestine elicited b! cholecystokinin preparations is due to the hormone itself and not to impurities in the preparations; this intestinal effect of cholecystokinin is mediated by another mechanism of action than the effect of the hormone on the gall‐bladder; cholecystokinin in low concentrations seems to have a specific effect on the proximal part of the intestine. It is possible that the hormone may play a role in the regulation of intestinal motility.

Effects of adrenocortical steroids on the propulsive motility of small intestine.

Adrenal cortex extract in low concentrations (1:1400–1:250) increases the peristaltic contractions of small intestine and restores to fatigued intestinal segments normal peristaltic activity and the ability to propel fluid against a pressure gradient, in vitro (modified Trendelenburg technique). Adrenal cortex extract in high concentrations (1:150–1:25) reversibly inhibits or abolishes peristalsis in vitro. In adrenalectomized rats in vivo, adrenal cortex extract increases the rate of propulsion of dyes along the small intestine in moderate doses (1 ml b.i.d.), and decreases propulsion in large doses (5 ml b.i.d.). Cortisone, hydrocortisone and corticosterone in the amounts present in stimulant doses of adrenal cortex extract had no effect on intestinal propulsion, in vivo. Doses of aldosterone (0.1 and 0.5 µg b.i.d.) comparable with the amounts contained in the extract used and large doses of the electrolyte-controlling steroids, desoxycorticosterone (2.5 and 5 mg) and corticosterone (2.5 mg), reproduced the stimulant effects of the extract, in vivo. It is possible that the effects of aldosterone may be of significance in controlling intestinal motility under physiological and some pathological conditions.

生薬中の微量成分の研究 (第9報)

In order to follow the course whereby acetylcholine appears in honey, honey bees were fed with sugar solution free from acetylcholine (glucose: fructose: water=3.5:3.5:3.0) and one added with 10γ/cc. of acetylcholine chloride, shut off from outside influence. Honey that accumulated in a new comb was collected and the presence of acetylcholine was examined by the Magnus method in both cases. The honey from bees fed on simple sugar solution clearly indicated contraction of guinea pig intestine, the amount of contraction being equal to about 0.2γ/cc. of acetylcholine. The one from bees fed on sugar solution containing acetylcholine showed a slightly stronger contraction than the former. From the present experimental results and those recorded in Part VIII of this series, it became clear that acetylcholine in honey is not derived from nectar of flowers or the pollens but is biogenetically formed in the honey bee itself and secreted into honey. Determination of acetylcholine in three different kinds of domestic Royal jelly by the paper chromatography and the Magnus method showed the content to be 1250-1625γ/g., an average of 1500γ/g., which is almost 100 times more than that in the honey. It was also confirmed that Royal jelly does not contain histamine and other factors which effects contraction of small intestine, acetylcholine being almost the only factor present.