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PubMed1977

Effects of intravenous calcitonin on water, electrolyte, and calcium movement across in vivo rabbit jejunum and ileum.

The influence of intravenously administered synthetic salmon calcitonin on water, electrolyte and calcium fluxes in in vivo rabbit jejunum and ileum was examined. Rabbits were divided into four groups: those receiving (1) saline intravenously while a glucose-free isotonic saline solution perfused the jejunum and ileum; (2) calcitonin intravenously while the same intestinal perfusate was used as in group 1; (3) intravenous saline while 10 mM glucose-isotonic saline solution perfused jejunum and ileum; and (4) intravenous calcitonin while the intestinal perfusate was of the same composition as in group 3. Calcitonin provoked a significant increase in jejunal and ileal water, sodium, and bicarbonate secretion in both the glucose-free and glucose-containing perfusate groups. No influence on calcium movement was noted. These results, similar to findings of Gray et al. (J Clin Invest 52:3084-3088, 1975) in human jejunum, suggest that calcitonin may play a role in the pathogenesis of the watery diarrhea noted in about one-third of patients with medullary carcinoma of the thyroid. In addition, these studies demonstrate the usefulness of the rabbit as an animal model with which to investigate further the effects of calcitonin upon intestinal fluid and electrolyte transport.

Animals↗

PubMed1977

[Pharmacological analysis of the pendular movements appearing during calcium blocking of peristalsis in the isolated guinea pig ileum].

Calcium chloride acting from the serosal surface blocked the peristaltic reflex and at the same time, after about 30 minutes, evoked pendulum type of activity in the longitudinal muscle of the guinea-pig isolated ileum, subjected to constant intraluminal pressure. Hexamethonium, tetraethylammonium, morphine, methadone and atropine blocked, while, neostigmine potentiated the pendulum movements evoked by calcium chloride. In the Magnus preparation of the guinea-pig isolated ileum calcium chloride also caused pendulum type of activity. From these experiments it is concluded that calcium chloride evoked pendular movements by stimulating the postganglionic cholinergic nerves in the longitudinal muscle of the guinea-pig isolated ileum.

Animals↗

PubMed1975

Interactions of morphine, adenosine, adenosine triphosphate and phosphodiesterase inhibitors on the field-stimulated guinea-pig ileum.

Inhibition of the electrically induced contractions of the guinea-pig ileum has been shown to be a reliable index to the relative potency of various narcotic analgesics. This property suggests that this preparation might be used as a model in attempts to elucidate the mechanism(s) by which morphine induces analgesia in the central nervous system. Since it has been demonstrated that some adenosine derivative may function as an endogenous inhibitory transmitter in the gut, the effects of adenosine, adenosine triphosphate (ATP) and morphine on the ileum were further characterized and compared. Morphine, adenosine and ATP produce a substantial inhibition of the isometric contractions induced by transmural field stimulation. The inhibition produced by each is antagonized by 2.5 times 10(-7) M tolazoline whereas that produced by ATP is potentiated by 4 times 10(-7) M 5-hydroxytryptamine. The inhibitory effects of morphine and ATP can also be markedly potentiated by two of the several phosphodiesterase inhibitors tested, Ro 20-1724 and dipyridamole. In addition, pretreatment of the ileum with either adenosine, ATP or morphine can produce a significant potentiation of the inhibitory effects of norepinephrine. The above suggests that cyclic adenosine 3',5'-monophosphate may play a role in mediating some of the inhibitory effects produced by exogenous adenosine, ATP and morphine. In addition, the similarities between the effects produced by these substances indicates that the biochemical pathways responsible for mediating the effects of each may share some common elements.

Adenosine↗

PubMed1976

Studies on the narcotic receptor in the guinea-pig ileum.

Studies were conducted on the development and loss of tolerance to morphine in the coaxially stimulated guinea-pig ileum. In ilea from guinea pigs made tolerant to morphine by the procedure of morphine-pellet implantation, the morphine-naloxone pA2 was decreased from 8.5 to 7.6, suggesting a qualitative rather than a quantitative change in the receptors. This change in the pA2 was in the opposite direction from that previously observed with analgesic receptors. Three hours after the administration of a single injection of morphine to the guinea pig, the ileum showed tolerance to morphine, which disappeared by 6 hours. With naloxone as the antagonist, the narcotic analgesics, morphine, methadone, etorphine and levorphanol, yielded higher pA2 values than the narcotic antagonist analgesics, nalorphine, pentazocine and cyclazocine, a result similar to that seen with the analgesic receptors. However, the interaction between naloxone and the narcotic antagonists in the ileum differed from that in the central nervous system when the slopes of the pAx plots were examined. Thus, although the interaction of analgesics with the ileal receptors appears to correlate with the acute effects of the drugs, caution must be exercised to use the ileal receptors as models of analgesic receptors for the study of chronic narcotic effects, i.e., tolerance and dependence.

Animals↗

PubMed1976

Influence of papaverine derivatives on phosphodiesterase activity, cyclic 3',5'-AMP levels and relaxing effect on rabbit ileum.

The correlations between the relaxing effect of papaverine derivatives, inhibition of low Km-phosphodiesterase (cAMP-PDE = EC 3.1.4.17) activity and cyclic 3',5'-AMP (cAMP) levels in isolated rabbit ileum were investigated. There was a strong correlation between the relaxing effect, inhibition of PDE activity and cAMP content for eupaverine, ethylpapaverine and papaverine. Eupaverine was the most effective relaxing agent (I50 = 7.5 muM) and the most potent inhibitor of PDE activity (Ki = 0.6 muM), followed by ethylpapaverine (I50 = 10 muM;Ki 0.8 muM) and papaverine (I50 = 20 muM;Ki = 2 muM). In contrast, there was a strong relaxing effect (I50 = 6 muM) but only slight inhibition of PDE activity (Ki = 350 muM) by tetrahydropapaveroline (THP). The adenylate cyclase stimulating effect of THP which was shown by others is most likely the reason for comparatively higher cAMP levels, which were found to be elevated about seven times over basal levels of 0.35 nmoles/g wet weight, and effective relaxation. Relaxation could be induced by exogenously added cAMP (I50 = 45 muM) and dibutyryl-cAMP (I50 = 450 muM). Our results support the assumption that smooth muscle relaxation in rabbit ileum is mediated by cAMP. Some of these observations have been published in abstract form (Schulz and Berndt, 1972).

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1979

The Schultz-Dale reaction of the guinea-pig ileum: influence by beta-adrenoceptor agonists and theophylline.

One of the organs that can be used to study the Schultz-Dale reaction, is the guinea-pig ileum. The reaction is characterized by a specific pattern: a quick contraction, followed by a quick relaxation and a second, more slow contraction. A description is given of this typical reaction. Selective inhibition of the slow contraction could be obtained using beta-adrenoceptor agonists. Also theophylline inhibited the slow contraction, but this inhibition was only selective within a narrow range of concentration. These findings encourage further investigation about a possible involvement of cyclic nucleotides in the liberation of the mediators involved in the Schultz-Dale reaction of the guinea-pig ileum. Furthermore they provide more information about this preparation which could be used as a screening model for anti-allergic drugs of distinct pharmacological groups.

Adrenergic beta-Agonists↗

PubMed1979

Relationship between histamine-induced changes of cyclic AMP and mechanical activity on smooth muscle preparations of the guinea-pig ileum and the rabbit mesenteric artery.

On guinea-pig ileum and rabbit mesenteric artery contracted by high potassium (100 mM) histamine produced relaxations which were inhibited by the H2-receptor antagonist metiamide. These results are thus indicative for the role of H2-receptors in mediating relaxation and for H1-receptors in mediating contraction on smooth muscle. Time course studies for the relaxing and cyclic AMP responses to histamine showed that the cyclic AMP increase preceded the H2-receptor mediated relaxation. The cyclic AMP increase in response to histamine was prevented by metiamide, but remained unaffected by mepyramine on both the guinea-pig ileum and the rabbit mesenteric artery. In addition, dose-response curves obtained on the mesenteric artery demonstrated that the H2-receptor mediated depressor responses coincided with cyclic AMP increases. Thus, these results gave clear-cut evidence that cyclic AMP is an intracellular metabolic event only implicit in the H2-receptor mediated relaxation, but not in the H1-receptor mediated contraction on smooth muscle preparations.

Animals↗

PubMed1979

Electromotor feeding responses of primate ileum and colon.

Serosal bipolar electrodes to record spike discharges and strain gauge force transducers to record circular muscle contractions were placed in pairs on the terminal ileum, cecum, right colon at the ileocecal valve, ascending colon, and proximal transverse colon of sixteen primates. After an overnight fast, electromotor responses to continued fasting or to ingestion of a meal (randomized order) were recorded in awake animals. Feeding led to increased spike discharges and increased frequency of muscle contractions at all sites. The onset of these responses usually was within 6 minutes after feeding; the responses increased progressively during 30 to 45 minutes and then remained more or less at a constant plateau of increased activity. Atropine completely blocked the postcibal responses of ileum and proximal colon for up to 30 minutes. Transit time data of labeled meals excluded direct stimulation by a food bolus as the mechanism of the observed postcibal colonic response. The pattern of response was consistent with humoral mediation.

Animals↗

PubMed1975

D-galactose accumulation in rabbit ileum. Effects of theophylline on serosal permeability.

The effects of theophylline and dibutyryl cyclic AMP, on in vitro unidirectional galactose fluxes across the mucosal and serosal borders of rabbit ileum have been studied. 1. When Ringer [galactose] = 2mM, theophylline and dibutyryl cyclic AMP reduce both mucosal-serosal and serosal-mucosal galactose flux by approx. 50%. The K1 for theophylline inhibition of flux in both directions is 2 mM. 1 mM dibutyryl cyclic AMP elicits a maximal inhibitory response. Concurrent with the inhibition in transmural galactose fluxes, theophylline and dibutyryl cyclic AMP increase the tissue accumulation of [galactose] and the specific-activity ratio R of 3H : 14C-labelled galactose coming from the mucosal and serosal solutions respectively. It is deduced that theophylline and dibutyryl cyclic AMP are without effect on the mucosal unidirectional permeability to galactose but cause a symmetrical reduction in serosal entry and exit permeability. 2. Reduction in the asymmetry of the mucosal border to galactose by reducing Ringer [Na], raising Ringer [galctose] or adding ouabain reduces the theophylline-dependent increase in galactose accumulation. 3. Hypertonicity in the serosal solution increases the permeability of the serosal border to galactose and reduces tissue galactose accumulation. Serosal hypertonicity partially reverses the theophylline-depedent effects on galactose transport. Replacing Ringer chloride by sulphate abolishes the theophylline-dependent effects on galactose transport. 4. It is considered that the theophylline-dependent increase in galactose accumulation results from the reduction in serosal permeability. This is shown to be a quantitatively consistent inference. 5. Further support for the view that the asymmetric transport of galactose in rabbit ileum results from convective-diffusion is presented.

Animals↗

PubMed1976

Effects of methylxanthines and imidazole on the contractions of guinea-pig ileum induced by transmural stimulation.

Methylxanthines (10(-5) to 10(-3)M) were found to increase the amplitude of contractions of guinea-pig ileum induced by transmural stimulation but to inhibit those induced by acetylcholine or histamine. The order of the abilities of methylxanthines to augment the contractile responses was theobromine greater than caffeine greater than theophylline. When the contractions were completely suppressed by reduction of the calcium content in the medium or by addition of cyclic AMP, methylxanthines restored the responses effectively, just as does addition of calcium. Methylxanthines also accelerated the release of acetylcholine from the ileum associated with stimulation. Imidazole (3 X 10(-5) to 10(-3) M) had an essentially similar effect to methylxanthines in potentiating the contractile responses and in augmenting the release of acetylcholine. The present results indicate that the potentiating effects of methylxanthines and imidazole are due to an action on the nerve terminals, not on the postsynaptic membranes or contractile elements. Therefore, it si concluded that theit potentiating actions are due to facilitation of the movement of calcium in the nerve terminals on excitation, resulting in increased release of acetylcholine, and are not due to the effect of cyclic AMP formed as a result of their inhibitory actions on phosphodiesterase.

Animals↗

PubMed1977

The interaction of 1-(2(diarylmethoxy)ethyl)aziridines with histamine receptors in the longitudinal muscle strip of the guinea pig ileum.

The time course of the onset and decline of histamine antagonism by 1-(2-(diarylmethoxy)ethyl)aziridines, compounds which could be expected to have H1-receptor alkylating properties, was investigated on the longitudinal muscle strip of the guinea pig ileum. Experiments were performed with normal preparations and with muscle strips pretreated with a prostaglandin synthesis inhibitor in order to prevent spontaneous rise of muscle tone. In contrast to the previously reported observation that antihistaminic potency decreased with prolongation of the preincubation time, histamine antagonism by the aziridine compounds remained at a constant level for more than 60 min in the presence of indomethacin. This indicated that the aziridines are not hydrolyzed either directly in solution or after interaction with the tissue since the supposed hydrolysis product had a significantly lower antihistaminic activity. A comparison between 1-(2-diphenylmethoxy)ethyl)aziridine and diphenhydramine showed the former compound to have a slightly more rapid onset and a considerably more rapid decline of histamine receptor blockade. It was concluded that 1-(2-(diarylmethoxy)ethyl)aziridines did not alkylate the histamine H1-receptor in the longitudinal muscle layer of the guinea pig ileum.

Animals↗

PubMed1979

Effect of prostaglandin E1 and indomethacin on responses of longitudinal muscle of guinea-pig ileum to cholecystokinin.

The effect of prostaglandin E1 (PGE1) and indomethacin (IND) cholecystokinin (CCK)-induced contractions of guinea-pig isolated ileum longitudinal muscle were studied. PGE1 (2.8--28 nM) consistently and dose dependently increased the contractions evoked by CCK (indirect muscle stimulation) or by ACh. IND (2.7 microM) decreased the contractions to both compounds and this was reversed with 2.8--7 nM PGE1. Pretreatment of the preparations with phentolamine (2.6 microM) or pretreatment of the animals with reserpine (2 mg/kg i.p. 24 h before killing) did not affect PGE1 potentiation or IND inhibition of CCK-induced contractions. The results indicated that PGE1 potentiated CCK-induced contractions of the longitudinal muscle of guinea-pig ileum by increasing the response to released ACh. Experiments with IND suggested that endogenous PGs may modulate the effect of CCK or related gastrointestinal hormones.

Acetylcholine↗

PubMed1975

Papillary lymphoid hyperplasia of the terminal ileum: an unusual cause of intussusception and gastrointestinal bleeding in childhood.

Papillary lymphoid hyperplasia of the terminal ileum is a benign condition associated with abdominal pain, intussusception, and gastrointestinal hemorrhage. It appears to represent a distinct clinicopathologic entity, separate from the usual idiopathic intussusception of infancy and childhood. The lesions are reasonably well circumscribed, localized in the submucosa of the terminal ileum, and composed of lymphoid tissue with prominent germinal follicles. Management by ileocolectomy resulted in complete cure with no postoperative complications in our six cases. However, many authors recommend conservative therapy. The cause is not known but there may be some relationship between these cases and intestinal adenovirus infection.

Adenoviridae Infections↗

PubMed1975

Effects of cholecalciferol on the translocation of calcium by non-everted chick ileum in vitro.

An apparatus is described that allows perfusion of a non-everted segment of intestine in vitro and the study of the accumulation of substances within the mucosal cells. The translocation of Ca(2+) by rachitic-chick ileum and the effect of pretreatment with cholecalciferol was investigated, with the following conclusions. (1) Entry of Ca(2+) across the microvilli into mucosal cells is by diffusion; it does not require metabolic energy or the presence of any other inorganic ions. (2) Pretreatment of the chick with cholecalciferol causes increased permeability of the microvillus to Ca(2+) in both directions (lumen to cell, cell to lumen). The increased transport brought about by cholecalciferol in vivo can be partially mimicked by sodium dodecyl sulphate added in vitro. (3) The sign and the magnitude of the electrical potential difference prevailing across the ileum does not influence Ca(2+) transport. (4) Exit of Ca(2+) from the mucosal cell is temperature-sensitive, requires metabolic energy and Na(+). (5) Pretreatment with cholecalciferol caused increased movement of Ca(2+) out of the cell across the basement membranes. This effect of cholecalciferol given in vivo could be markedly increased by the presence of dicyclohexylcarbodi-imide in the perfusion fluid. These observations suggested that cholecalciferol increased Ca(2+) entry (and exit) at the mucosal surface and also caused Ca(2+) to be more available to the pump at the serosal surface.

Anaerobiosis↗

PubMed1978

Analytical subcellular fractionation studies on enterocytes from the jejunum and ileum of the rat and some properties of brush-border alkaline phosphatase.

1. Enterocytes, isolated from the proximal jejinum and distal ileum of the rat, were homogenized and their organelles separated by isopycnic centrifugation on continuous sucrose density gradients. The distributions of marker enzymes for the principal organelles, RNA and protein were determined in the sucrose gradients and related to the activities per entercocyte. 2. In the jejunum the modal equilibrium densities of the various organelles were: brush borders (1.20), lysosomes (1.20), peroxisomes (1.19), mitochondria (1.17) and basal-lateral membranes (1.13). The values were not significantly different in the ileum. The activities of brush-border enzymes, soluble and mitochondrial malate dehydrogenase, soluble and membrane-associated lactate dehydrogenase and particulate protein content, however, were greater in the jejunal than the ileal enterocytes. 3. Detergent exposed latent alkaline phosphatase activity in jejunal enterocytes and indicated that this enzyme is present not only in the brush border but also in the basal-lateral membrane and soluble fractions of the cell. 4. Isolated jejunal brush-border preprations showed latent activities of both alkaline phosphatase and gamma-glutamyltransferase whereas the activities of alpha-glucosidase and leucyl-beta-naphylamidase were not affected by detergent. Mechanical disruption of these preparations suggested the presence of two forms of alkaline phosphatase in the brush border and provides a technique to assess membrane fragility.

Alkaline Phosphatase↗

PubMedDate not supplied

[Protein digestibility and the absorption of amino acids in various segments of the digestive tract of pigs. 3. Results of the fractionation of ileum chyme after feeding various rations].

Growing female pigs provided with re-entrant ileum resp. ileocecal cannulae received 6 different rations (fattening feed I and II for pigs, rations with dried skim milk, wheat gluten + lysine resp. wheat + wheat gluten + lysine, N-free mixture). The ileum chyme was separated into the fractions supernatant 1 and sediment 1 and by a treatment of supernatant 1 with trichloracetic acid and subsequent centrifuging into supernatant 2 and sediment 2. In the complete chyme as well as in all fractions the crude protein and amino acid contents were determined. The distribution in per cent of the crude protein and the amino acids over the fractions was calculated as well. The influence of the rations, in particular rations of dried skim milk, on the amino acid pattern of the complete chyme and the chyme fractions could be established. An influence of the rations could not be recognised on sediment 2 only, which indicates a uniform amino acid pattern of these probably endogenous proteins. The percentage of crude protein and amino acids in the fractions was also influenced by the rations.

Amino Acids↗

PubMedDate not supplied

[Protein digestibility and the absorption of amino acids in various segments of the digestive tract of pigs. 4. Digestibility of crude protein and amino acids and rate of passage through the duodenum and ileum and the total digestive tract of growing pigs].

The crude protein digestibility and the amino acid absorption of six female pigs (average live weight 61 kg) with duodenal and ileocecal re-entrant cannulae, which were fed with a wheat + wheat gluten + lysine ration and an N-free ration, were determined in various segments of the intestines. Comparative experiments concerning the N-metabolism with pigs without and with cannulae showed that the animals renormalised their metabolism 14 days after narcosis and fistulation of the intestines. The extents of secretion and absorption of the various amino acids vary as it is shown from the values of the apparent and true digestibility resp. rate of passage through various segments of the intestines. While for methionine and glutamic acid absorption exceeds endogenous secretion already in the duodenum, the amino acids with a high endogenous quota (glycine, alanine, threonine, tryptophan) are, even at the terminal ileum, not as well absorbed as the others. Methionine is obviously synthesised on a large scale by the colon flora and excreted in feces. The fractionation of the duodenal and ileum chyme after feeding wheat + wheat gluten + lysine as well as N-free mixture, into the fractions "solid particles", "peptides-free amino acids" and "proteines precipitable by trichlor-acetic acid" supplies information on the degree of protein degradation in various segments of the intestines.

Amino Acids↗

PubMed1977

Regional localization of activity of Clostridium perfringens type A enterotoxin in the rabbit ileum, jejunum, and duodenum.

Rabbit ileal, jejunal, and duodenal loops were exposed to purified enterotoxin from Clostridium perfringens type A and then perfused for comparative analysis of effects of the enterotoxin on each region of the intestine. Ileal loops responded with enhanced net secretion of fluid and sodium, inhibition of chloride and glucose uptake, and substantial sloughing of epithelial cells. The jejunum responded with fluid secretion, enhancement of sodium secretion only during the first 20 min, inhibition of chloride and glucose uptake, and substantial sloughing of epithelial cells. In the duodenum, transport of fluid, sodium, and chloride was significantly altered only during the first 20 min of perfusion, and significant inhibition of glucose uptake varied from one period to another. Epithelial damage was much less than that seen in the jejunum or ileum. Levels of fluid protein in all three sections corresponded closely to extent of tissue damage. In general, it was found that the severity of response to fixed doses of enterotoxin varied as follows: ileum greater than jejunum greater than duodenum.

Animals↗