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PubMed2001

Functional properties of atypical beta-adrenoceptors on the guinea pig duodenum.

In this study, we attempted to further characterize atypical beta-adrenoceptors on the guinea pig duodenum. (-)-Enantiomers of isoprenaline and noradrenaline were more potent than its (+)-enantiomers. The isomeric activity ratios ((+)/(-)) were less than those obtained in the guinea pig atria and trachea. The concentration-response curves to catecholamines ((-)-isoprenaline, (-)-noradrenaline and (-)-adrenaline), to the selective beta(3)-adrenoceptor agonist, BRL37344 ((R*, R*)-(+/-)-4-[2-[(2-(3-chlorophenyl)-2-hydroxyethyl)amino]propyl]phenoxyacetic acid sodium), and to the non-conventional partial beta(3)-adrenoceptor agonist, (+/-)-CGP12177A ((+/-)-[4-[3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-1,3-dihydro-2H-benzimidazol-2-one] hydrochloride), were resistant to blockade by (+/-)-pindobind, the beta-adrenoceptor alkylating agent. (-)-Noradrenaline and (-)-adrenaline were more potent than dopamine and (-)-phenylephrine, respectively. Selective beta(2)-adrenoceptor agonists possess agonistic activities at atypical beta-adrenoceptors. (+/-)-Propranolol and (+/-)-bupranolol had no agonistic effect, whereas (+/-)-alprenolol, (+/-)-pindolol, (+/-)-nadolol, (+/-)-CGP12177A and (+/-)-carteolol exhibited agonistic activities at atypical beta-adrenoceptors. These results suggest that pharmacological properties of atypical beta-adrenoceptors differ from those of conventional beta(1)- and beta(2)-adrenoceptors on the guinea pig.

Adrenergic beta-Agonists↗
PubMed1996

Differential ontogeny of adenosine receptors in the longitudinal muscle and muscularis mucosae of the rat isolated duodenum.

The ontogeny of P1 purinoceptors in the separated layers of the rat duodenum was investigated using functional assays. In the longitudinal muscle N6-cyclopentyladenosine (CPA) caused relaxations from day 20 that were inhibited by 1,3-dipropyl-8-cyclopentyl-xanthine (DPCPX) (10 nM) indicating an action via adenosine A1 receptors. 5'-N-ethylcarboxamidoadenosine (NECA) caused relaxations at day 15 that were inhibited by DPCPX (1 microM) while 2-p-(2-carboxyethl)phenylethylamino-5'-N-ethylcarboxamidoade nosine (CGS 21680) was almost inactive, indicating an action at adenosine A2B receptors. From day 20 NECA was inhibited by DPCPX (10 nM) but was not antagonised by DPCPX (1 microM) to the extent expected for an adenosine A1 receptor, suggesting activation of adenosine A1 and adenosine A2B receptors. In the muscularis mucosae, CPA and NECA caused contractions from day 10 inhibited by DPCPX (1 microM) while CGS 21680 was less potent, indicating activation of adenosine A2B receptors. These results show that adenosine A2B receptors are present early in the postnatal period, whereas adenosine A1 receptors develop after day 20.

Adenosine↗
PubMed1999

Abnormal clearance of exogenous acid and increased acid sensitivity of the proximal duodenum in dyspeptic patients.

BACKGROUND & AIMS: Although acid is likely to play a role in the genesis of symptoms in dyspeptic patients, most studies have failed to show an increase in gastric acid secretion. The aim of this study was to investigate clearance of acid from the duodenum and its relationship with symptoms in patients with functional dyspepsia. METHODS: Twelve patients and 10 healthy volunteers were studied using an assembly allowing recording of pressures and pH. Acid and saline were infused intraduodenally during phase II and postprandially. Sensations were scored before and 1 and 5 minutes after each infusion. RESULTS: After acid infusion in the fasting period, a greater increase in acidity in the duodenal bulb (P = 0.007) and fewer duodenal pressure waves (P = 0.002) were observed in dyspeptic patients. No significant differences in the time with pH < 4 and duodenal motor activity were observed in the postprandial period. Acid infusion reproducibly increased the sensation of nausea in patients (P < 0.001) but not in the controls. Saline infusion had no effect on upper gastrointestinal sensations. CONCLUSIONS: In fasting dyspeptic patients, clearance of exogenous acid from the duodenal bulb and duodenal motor activity are decreased. The duodenal bulb in dyspeptic patients is hypersensitive to acid infusion, which induces the nausea.

Adult↗
PubMed1985

Angiodysplasia of the stomach and duodenum.

Twenty-five angiodysplasias in the stomach and duodenum were identified with endoscopy in 12 patients. The average age of the patients was 70 years. Two patients had aortic stenosis. Six of the patients were treated with electrocoagulation, three of whom required surgery. Angiodysplasia of the upper gastrointestinal tract is considered to be more common than previously thought and an important cause of both obscure and overt bleeding.

Adult↗
PubMed1998

A prospective endoscopic study of scalloped folds and grooves in the mucosa of the duodenum as signs of villous atrophy.

BACKGROUND: Scalloping of the valvulae conniventes visible at endoscopy may predict the presence of villous atrophy. This prospective study was designed to discover how commonly duodenal mucosal scallops and grooves occurred and to delineate their relationship to villous atrophy. METHODS: All patients undergoing upper gastrointestinal endoscopy by a single observer over 5 years were included. After inspection of the duodenal mucosa, biopsy samples were taken from those in whom the mucosa was abnormal (n = 26) and from those in whom it was not, but where biopsy was indicated (n = 100). RESULTS: None of the 100 endoscopically normal controls had subtotal villous atrophy: 94 had normal histology, 2 had non-atrophic change, and 4 had partial villous atrophy; 14 of the 26 individuals (54%) with abnormal duodena had subtotal villous atrophy, 7 having both scallops and grooves. Four had scallops alone, and three had grooves only. All patients with both scallops and grooves had subtotal villous atrophy (100%), the positive predictive value of which was 36% for scallops alone and 38% for grooves alone. CONCLUSIONS: Scallops and grooves together indicate that subtotal villous atrophy is very likely histologically, even when that diagnosis has not been suspected. A normal duodenum excludes it.

Adult↗
PubMed1999

Hemorrhage and renal ischemia-reperfusion upregulates the epidermal growth factor receptor in rabbit duodenum.

To study the role of EGF-R in small intestinal adaptation to hemorrhage and I/R, anesthetized rabbits were implanted aseptically with arterial and venous catheters and bilateral renal artery Doppler flow probes and silastic occluders and allowed to recover. Rabbits were then randomly assigned to one of six groups: time control; hemorrhage (22.5 mL/kg) and 2.5 hours of renal occlusion (hemorrhage plus I/R); hemorrhage plus I/R and 2:1 LRS resuscitation; hemorrhage plus I/R and 3:1 LRS resuscitation; hemorrhage alone; or I/R alone. Rabbits were killed 48 hours after hemorrhage, and a section of duodenum was collected for analysis. Hemorrhage plus I/R induced a 2.5-fold increase in EGF-R tyrosine kinase activity compared with that found in the control group (P < .05), and this effect was not modified by either LRS resuscitation regimen. This increased activity was associated with similar Increases in EGF-R protein concentrations and approximately a 50% increase in EGF-R messenger (m)RNA levels compared with levels found in the control group. Further analysis of possible regulatory mechanisms for the increased EGF-R expression after hemorrhage plus I/R detected higher levels of EGF-R phosphorylation compared with those found in the control group but no significant increases in transforming growth factor-alpha mRNA levels. These data, coupled with a significant increase in duodenal thlobarbituric acid-reactive substance concentrations from rabbits in the hemorrhage plus I/R group, support the hypothesis that tyrosine kinase signal transduction pathways involving the EGF-R are activated in the small intestine after hemorrhage, renal I/R, or both, and this process may be mediated, at least in part, by oxidant stress.

Animals↗
PubMed1998

Effects of pituitary adenylate cyclase activating polypeptide-27 on alkaline secretory and mucosal ulcerogenic responses in rat duodenum.

Effects of pituitary adenylate cyclase activating polypeptide (PACAP) on duodenal mucosal HCO3- secretion and ulcerogenic responses induced by mepirizole in anesthetized rats were examined and compared with those of vasoactive intestinal polypeptide (VIP). Animals were given mepirizole (200 mg/kg, s.c.) for induction of duodenal ulcers, and gastric acid and duodenal HCO3- secretions were measured with or without pretreatment of PACAP-27 or VIP. Mepirizole increased acid secretion and induced hemorrhagic lesions in the proximal duodenum within 6 h. Intravenous bolus injection or infusion of PACAP-27 (4 and 8 nmol/kg or 8 nmol/kg/h) increased duodenal HCO3- secretion even in the presence of mepirizole, without effect on acid secretion, and significantly reduced the severity of duodenal lesions caused by mepirizole. In contrast, VIP (8 nmol/kg, i.v.) given by bolus injection significantly decreased acid secretion induced by mepirizole, in addition to stimulation of HCO3- secretion, and prevented duodenal lesions in response to mepirizole. These results suggest that PACAP-27 increases duodenal HCO3- secretion and this action may be important in maintaining the duodenal mucosal integrity against acid, and VIP affords duodenal protection by both increasing duodenal HCO3- secretion and decreasing acid secretion. The reason for the different effects of PACAP and VIP on acid secretion is unknown.

Animals↗
PubMed1999

Coordinated distribution patterns of three enzyme activities involved in the absorption and metabolism of beta-carotene and vitamin A along the villus-crypt axis of chick duodenum.

The conversion of beta-carotene to retinal and the succeeding metabolic process of the retinal leading to production of retinol and retinyl esters are the prerequisite for the utilization of beta-carotene as a provitamin A. These processes are participated by beta-carotene cleavage enzyme, retinal reductase and retinol esterifying enzyme(s) in the small intestine. To examine whether these enzymes exhibit the coordinated distribution in the villus, we have used the cryostat sectioning technique to quantify the activities of beta-carotene cleavage enzyme, retinal reductase and retinol esterifying enzymes along the villus-crypt axis in 8-day-old chick duodenum. The beta-carotene cleavage enzyme activity was very low in the crypt and gradually increased, reaching a maximum in the mid-villus. The villus-crypt gradient of the beta-carotene cleavage enzyme activity corresponded with those of retinal reductase activity and lecithin: retinol acyltransferase (LRAT) activity, but distinct from that of acyl-CoA: retinol acyltransferase (ARAT) activity. Furthermore, the distribution of the content of retinyl esters was similar to that of LRAT activity. These results suggest that the beta-carotene cleavage enzyme is coordinately distributed along the villus-crypt axis with retinal reductase and LRAT, the two enzymes which require cellular retinol-binding protein, typeII (CRBPII) as the donor of the substrate.

Acyltransferases↗
PubMed1982

Mucosal biopsy of the esophagus, stomach, and proximal duodenum.

The past decade has occasioned the development and extensive use of flexible endoscopes for visualization of large areas of the alimentary tract. Numerous small grasp biopsies are now performed to determine the diagnosis and course of a large variety of inflammatory and neoplastic disorders. In this review, the authors have concentrated on the uses and interpretation of endoscopy and biopsy of the upper alimentary tract including the esophagus, stomach, and proximal duodenum. They have also commented on the limitations of endoscopic biopsy with respect to its size, superficial nature, and imperfect orientation in the evaluation of some disorders.

Biopsy↗
PubMed1999

Ageing and endocrine cells of human duodenum.

Motility and secretory disorders of the gastrointestinal tract and associated glands increase with ageing. The duodenum contains several peptide/amine producing cells that play an important role in regulating gastrointestinal motility and secretion. The present study was performed to elucidate changes in these cells that may have arisen as a result of ageing. A total of four age groups of subjects, aged 1-2, 20-29, 40-49 and 60-69 years were studied. The various endocrine cell types were identified by immunohistochemistry and quantified by computerized image analysis, and two parameters were determined; the number of cells/mm3 epithelial cells and the cell secretory index (CSI), which indicates the immunoreactive secretory granule content of the endocrine cells. Chromogranin A- and serotonin-immunoreactive (IR) cells were fewer in 1-2-year-olds than in 20-29-year-olds. Gastrin/CCK-IR cells were significantly more numerous in 1-2-year-olds and 60-69 years-olds than in 20-29-year-olds. Somatostatin-IR cells were more numerous in the 40-49-year-olds than in the 20-29 years-olds. The CSI was higher in chromogranin A-, gastric inhibitory polypeptide (GIP)-, somatostatin- and gastrin/CCK-IR cells in 1-2-year-olds than in 20-29-year-olds. There was no significant sex difference regarding the numbers and CSI of other endocrine cell types. This study established the absence of sex-related differences in all endocrine cell types investigated, regarding numbers and physiological activity. Age, on the other hand, was shown to be associated with changes in the numbers of CCK-, somatostatin- and serotonin-IR, which may have some bearing on the gastrointestinal disorders of the elderly.

Adult↗
PubMed1998

The deep muscular plexus of the pig duodenum: a histochemical and ultrastructural study with special reference to the interstitial cells.

The aim of the present study was to describe the deep muscular plexus of the pig duodenum and to characterize its cellular components. Numerous nerve varicosities have been detected in the deep muscular plexus using anti-synaptophysin antibodies. Nerve fibres were also detected here in the outer circular muscle layer, whereas no nerve fibres were observed in the inner circular muscle layer. In the deep muscular plexus, nerve fibres projected to interstitial cells which were characterized at the ultrastructural level. The interstitial cells were of two kinds: the interstitial fibroblastic-like cells (FLC) and the interstitial dense cells (IDC), both of which were interposed between nerve fibres and smooth muscle cells. The FLC were characterized by their elongated bipolar shape, the lack of basal lamina, a well-developed endoplasmic reticulum, a Golgi apparatus, and intermediate filaments. They were closely apposed to axon terminals containing small clear synaptic vesicles and/or dense-cored vesicles. They were frequently connected to each other and to smooth muscle cells of the inner and outer circular layer by desmosomes and more rarely by gap junctions. The IDC are myoid-like cells. They had a stellate appearance and were characterized by a dense cell body, numerous caveolae, and a discontinuous basal lamina. The IDC were always closely apposed to nerve fibres and were connected to smooth muscle cells by desmosomes and small gap junctions. The present results show the unique pattern of cellular organization of the deep muscular plexus of the pig small intestine. They suggest that the interstitial cells in the deep muscular plexus are involved in the integration and transmission of nervous inputs from myenteric neurons to the inner and outer circular muscle layers. The clear-cut distinction observed here between the two types of interstitial cells (fibroblastic and myoid-like) suggests that the interstitial cells of each type may also be involved in some other specific activity, which still remains to be determined.

Animals↗
PubMed2000

Parallel increase in substance P and VIP in rat duodenum in response to irradiation.

Irradiation was administered to the upper abdomen of rats, whereupon the duodenum was examined. Numerous vasoactive intestinal peptide (VIP)- and substance P (SP)-like immunoreactive nerve fibers were seen in the damaged mucosa, often in close association to each other. The intensity of the SP- and VIP-like immunoreaction was increased in several of the tissue compartments and, as measured with radioimmunoassay, the contents of SP- and VIP-like materials were increased after 30 Gray. The results show that SP and VIP levels increase after irradiation and suggest that SP and VIP are involved in interactive reactions in the reorganization and inflammatory processes in the gut after abdominal irradiation.

Animals↗
PubMed1999

Late recurrence of liposarcoma simulating adenoma of the duodenum.

A large pedunculated, polypoid mass in the duodenum of a patient with asymptomatic anaemia, with mucosal biopsies indicating a villous adenoma, turned out to be a liposarcoma during laparotomy. The patient had had a completely resected retroperitoneal liposarcoma 8 years before. Liposarcoma recurrence should be highly suspected even in case of atypical presentation and long disease free interval.

Adenocarcinoma↗
PubMed1998

Histamine receptor-independent muscle relaxation elicited by a series of histamine H2-receptor agonists on the isolated guinea pig duodenum: a study into the mechanism of action.

1. The histamine H2 receptor agonists, dimaprit, impromidine, amthamine, and several dimaprit- and impromidine-analogues were investigated for their spasmolytic activity on the guinea pig duodenum, precontracted with acetylcholine or KCl. 2. Almost all the H2 receptor agonists exerted a histamine H2 receptor-independent muscle relaxation, which was more evident on acetylcholine- than on KCl-precontracted preparations. 3. The relaxing activity of these compounds was independent of inhibitory receptors, like beta-adrenergic, GABA-ergic, serotoninergic, etc. Similarly, modifications of cyclic nucleotide metabolism and nitric oxide production did not appear to be involved. 4. The behavior of histamine H2-receptor agonists was shared only by the Na+-blocker procaine, the intracellular Ca2+-antagonist ruthenium red and, at least in terms of efficacy, by the protein kinase C inhibitor, chelerithrine. 5. This spasmolytic effect is probably due to an impairment of receptor-mediated depolarization at the plasma membrane level and/or an inhibitory activity on the protein kinase C-dependent activation of the contractile machinery. 6. Finally, our findings suggest that the histamine H2 receptor-independent muscle relaxation is a general feature shown by H2 receptor agonists endowed with different chemical structure and the putative spasmolytic "receptor" prefers a (substituted) thiazole over a (substituted) imidazole.

Animals↗
PubMedDate not supplied

Bicarbonate stimulatory action of nizatidine, a histamine H(2)-receptor antagonist, in rat duodenums.

Nizatidine, a histamine H(2)-antagonist, is known to inhibit acetylcholinesterase (AChE) activity and is used clinically as a gastroprokinetic agent as well as the anti-ulcer agent. We examined whether or not nizatidine stimulates duodenal HCO(3)(-) secretion in rats through vagal-cholinergic mechanisms by inhibiting AChE activity. Under pentobarbital anesthesia, a proximal duodenal loop was perfused with saline, and the HCO(3)(-) secretion was measured at pH 7.0 using a pH-stat method and by adding 10 mM HCl. Nizatidine, neostigmine, carbachol, famotidine or ranitidine was administered i.v. as a single injection. Intravenous administration of nizatidine (3-30 mg/kg) dose-dependently increased the HCO(3)(-) secretion, and the effect at 10 mg/kg was equivalent to that obtained by carbachol at 0.01 mg/kg. The HCO(3)(-) stimulatory action of nizatidine was observed at the doses that inhibited the histamine-induced acid secretion and enhanced gastric motility. This effect was mimicked by neostigmine (0.03 mg/kg) and significantly attenuated by bilateral vagotomy and pretreatment with atropine but not indomethacin. The IC(50) of nizatidine for AChE of rat erythrocytes was 1.4 x 10(-6) M, about 12 times higher than that of neostigmine. Ranitidine showed the anti-AchE activity and increased duodenal HCO(3)(-) secretion, similar to nizatidine, whereas famotidine had any influence on neither AChE activity nor the HCO(3)(-) secretion. On the other hand, duodenal damage induced by acid perfusion (100 mM HCl for 4 h) in the presence of indomethacin was significantly prevented by nizatidine and neostigmine, at the doses that increased the HCO(3)(-) secretion. These results suggest that nizatidine increases HCO(3)(-) secretion in the rat duodenum, mediated by vagal-cholinergic mechanism, the action being associated with the anti-AChE activity of this agent.

Acetylcholinesterase↗
PubMed2002

Mixed function oxidases in kidney and duodenum of camel, guinea pig and rat.

The activities of the drug-metabolizing enzymes, aniline 4-hydroxylase, benzphetamine N-demethylase and 7-ethoxycoumarin O-deethylase have been measured in vitro in kidneys and duodenum of camels (Camelus dromedarius), guinea pigs (Cavia porcellus) and rats (Rattus norvegicus). In these species, levels of hepatic microsomal parameters namely microsomal protein, cytochrome P(450), cytochrome b(5) and NADPH-cytochrome c reductase have also been determined. In general, camels seemed to have the lowest enzyme activity when compared to rats and guinea pigs. Rats showed the highest activity in NADPH-cytochrome c reductase, aniline 4-hydroxylase and ethoxycoumarin O-deethylase among these species. However, guinea pigs showed the highest enzyme activity in cytochrome P(450), cytochrome b(5) and benzphetamine N-demethylase.

Animals↗
PubMed1998

Modulation of bicarbonate secretion in rabbit duodenum: the role of calcium.

Surface epithelial bicarbonate secretion protects the proximal duodenum from acid peptic injury. Cyclic adenosine monophosphate and calcium serve as intracellular mediators of intestinal transport. Experiments were performed to examine whether calcium participates in duodenal bicarbonate transport. Stripped duodenal mucosa from rabbits was studied in Ussing chambers. HCO3- transport was stimulated by the calcium ionophore A23187, carbachol, vasoactive intestinal peptide, prostaglandin E2, dibutyryl-cyclic adenosine monophosphate, and electrical field stimulation. A23187 stimulated HCO3- secretion and Isc; tetrodotoxin failed to inhibit this effect. The calcium-channel blocker verapamil abolished HCO3- secretion stimulated by carbachol, vasoactive intestinal peptide, and electrical field stimulation, but failed to alter basal, prostaglandin E2- or dibutyryl-cyclic adenosine monophosphate-stimulated HCO3- secretion. Therefore, calcium is likely required during stimulation of duodenal epithelial HCO3- transport by carbachol, vasoactive intestinal peptide, and electrical field stimulation. Prostaglandin E2 and dibutyryl-cyclic adenosine monophosphate appear to activate duodenal HCO3- secretion by a calcium-independent pathway(s).

Animals↗