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Neurotensin: dual effect on the motor activity of rat duodenum.

The effects of neurotensin on mechanical activity of rat duodenum were investigated using an isometric-isovolumic preparation. Neurotensin (1 pM to 10 nM) induced a concentration-dependent, tetrodotoxin (TTX)-insensitive fall in both endoluminal pressure and isometric tension. At higher concentrations of neurotensin (1 nM to 1 microM) the relaxation was followed by a concentration-dependent TTX-insensitive contraction, detected only by an increase in endoluminal pressure. Different concentrations of neurotensin were required to desensitize the relaxant and the contractile actions of the neuropeptide. The relaxation was antagonized by apamin, while the contractile response was blocked by nifedipine. Neurotensin, when tested separately on longitudinal and circular muscular strips, caused relaxation of the longitudinal strips. Circular strips showed contractions in response to neurotensin, following an inhibitory phase, if the strips were spontaneously or pharmacologically activated. The results suggest the presence of two sets of neurotensin receptors with a differential localization between the two muscular layers in rat duodenum.

Animals↗

Rat duodenum nitrergic-induced relaxations are cGMP-independent and apamin-sensitive.

The effects of the K+ channel blockers, apamin, tetraethylammonium and 4-aminopyridine, upon the relaxations of the isolated rat proximal duodenum induced by nitregic nerve activation, nitric oxide (NO), the NO donor 3-morpholinosydnonimine (SIN-1) and Br-cyclic GMP were determined. The effects of the guanylate cyclase inhibitors, cystamine and N-methylhydroxylamine, on NO-, SIN-1- and nitrergic nerve-induced responses were also investigated. Apamin inhibited nitrergic nerve-, NO-and SIN-1-induced relaxations but did not affect those induced by Br-cGMP. Tetraethylammonium and 4-aminopyridine as well as cystamine and N-methylhydroxylamine failed to affect the relaxations caused by any of the agents tested. These findings indicate that, in the rat proximal duodenum, nitrergic nerve activation as well as exogenous nitric oxide cause relaxation through a cGMP-independent, apamin sensitive mechanism.

4-Aminopyridine↗

Diffuse somatostatin-immunoreactive D-cell hyperplasia in the stomach and duodenum.

This paper presents the first case of extensive, diffuse, somatostatin-immunoreactive D-cell hyperplasia in the human stomach and duodenum. It occurred in a 37-yr-old woman, who showed clinical signs of dwarfism, obesity, dryness of the mouth, and goiter. The density of the distribution of D cells was increased 39-fold in the stomach fundus, 23-fold in the proximal antrum, 25-fold in the distal antrum, and 31-fold in the upper duodenum in comparison with normal values. At the same time, the gastrin-immunoreactive cells were increased 2.3-fold in the antrum. Although the range in size of the D cells was within normal limits in all regions examined, the G cells showed pronounced hypertrophy of up to 127%. A possible relationship between the immuno-histochemical findings and the clinical picture is discussed.

Adult↗

Hormonal control of opossum sphincter of Oddi motility: role of myoneural continuity to duodenum.

Motilin and caerulein are known to affect motility of the sphincter of Oddi (SO) and the gastrointestinal tract. The role of SO-duodenal myoneural continuity in the action of these peptides was studied. Five opossums had translocation of the duodenal papilla into the jejunum, while preserving the blood supply to the SO and duodenum. Serosal electrodes were placed in the SO, duodenum, and jejunum. Five control animals had electrode placement alone. Myoelectric recording was obtained during fasting and after administration of motilin (400 ng/kg) or caerulein (500 ng/kg/hr). Motilin induced premature phase III-like activity in the SO and intestine in controls. After the translocation of the papilla, the spike frequencies during phase II and phase III were significantly lower than in controls, whereas those during phase I and phase IV were not different. Motilin caused premature intestinal phase III and increased SO spike activity. However, the increase in SO spike activity was insufficient to form phase III. Caerulein produced a sustained increase in spike activity in both regions in both groups, but the increase was less in the translocation group than in controls. These data suggest that duodenal activity stimulated by motilin and caerulein participates in the activation of SO motility via intrinsic myoneural pathways.

Animals↗

Identification of the tridecapeptide dynorphin B (rimorphin) within perikarya of rat duodenum.

Using an immunofluorescence microscopic staining technique, the opioid peptide dynorphin B (rimorphin) was revealed within neuronal cell bodies of the rat duodenum. Dynorphin B immunoreactive perikarya were revealed in the myenteric and submucousal plexus as well as in the longitudinal muscle layer. They were large in diameter and round in shape and they contained a large round nucleus. Because no dynorphin B immunofluorescent nerve fibre and terminal could be noted it might be that dynorphin B is further cleaved by proteases into the bioactive opioid pentapeptide Leu-enkephalin and dynorphin B(6-13). These findings might also indicate that dynorphin B is processed within duodenal perikarya and that it has important physiological roles in the rat duodenum.

Animals↗

Possible role of the duodenum in the entero-PP axis.

The plasma pancreatic polypeptide response to a meal was compared in 6 healthy controls and 30 patients with gastric cancer who had undergone either subtotal gastrectomy or total gastrectomy with radical lymph node dissection including sympathectomy. Twelve patients were reconstructed with Billroth I, 9 patients with Billroth II, 6 patients with a double tract, and 3 patients with Roux-en-Y. Ten patients with a gastric ulcer who had undergone Billroth I gastrectomy including pyloric ring preservation also were examined. Impaired pancreatic polypeptide secretion was noted only in Billroth II and Roux-en-Y patients, where the duodenum is not affected by the passage of meals. Billroth I and double tract patients, in contrast, and an enhanced pancreatic polypeptide secretion. However, in BI patients with pyloric ring preservation the PP response to a meal was almost normal. These findings suggest an important role of the duodenum in the entero-PP axis in man.

Adult↗

Gastrin-releasing peptide stimulates cholecystokinin secretion in perfused rat duodenum.

We examined the effect of porcine gastrin-releasing peptide (GRP-27) and other analogous neuropeptides on cholecystokinin (CCK) secretion from the isolated perfused rat duodenum. GRP-27 stimulated CCK secretion in a monophasic pattern and in a dose-dependent manner ranging from 10(-9) M to 10(-6) M, and 10(-7) M of GRP-27 led to an increment of 442 +/- 120.8 fmol/3 min. The stimulatory effect of GRP-27 on CCK was not inhibited by 10(-5) M of atropine. 10(-7) M of neuromedin C and B, analogs of GRP, stimulated CCK secretion to increments of 382 +/- 64.1 and 289 +/- 47.2 fmol/3 min, respectively. Carbachol (10(-9) to 10(-6) M), VIP (10(-9)M), secretin (10(-9)M) and glucose (11 mM) did not stimulate CCK secretion, and the addition of atropine (10(-5)M) to them led to no significant changes. These results suggest that GRP may directly stimulate CCK secretion from the duodenum and work as a non-cholinergic, peptidergic neurotransmitter.

Animals↗

Ontogeny of gastrin and cholecystokinin in the colon and duodenum of sheep.

The different roles of gastrin and cholecystokinin in the fetus compared to the adult may be reflected in different distribution patterns. Re-expression of these fetal patterns is often seen in tumours of the adult. Using region-specific antisera and chromatography, we have determined the ontogeny of amidated gastrin (G-amide), glycine extended gastrin (G-gly), and cholecystokinin (CCK) in various segments of the colon and compared it to the developmental profile in the duodenum. Fetal sheep aged 80-90, 115-125 and 135-144 days (term is 145 days), 7-14 day lamb, and adult sheep were examined. In the colon, higher concentrations of G-amide (2.8 +/- 0.2 pmol/g) and CCK (11.7 +/- 1.6 pmol/g) were measured in the fetus while G-gly (0.7 +/- 0.1 pmol/g) was higher in the adult compared to other age groups. The calculated G-gly/G-amide ratio was 0.4 in the fetus and 1.4 in the adult while the CCK/G-amide ratios were 5 in the fetus and 13 in the adult. The duodenum of the lamb rather than the fetus contained the highest concentrations of G-amide, G-gly and CCK (40.3 +/- 9.7, 2.0 +/- 0.4, 109.0 +/- 14.3 pmol/g, respectively) and at concentrations exceeding that in the colon. The results demonstrate two major developmentally regulated features. Firstly as the colon matures, there is a gradual switch between the expression of the gastrin and CCK genes and secondly, the processing to G-amide is attenuated. These findings suggest that non-amidated gastrin should be examined for a potential role as a growth factor in colorectal carcinogenesis.

Animals↗

Retention of cadmium in the duodenum of the rat following oral administration.

The retention of cadmium in selected organs of the rat was studied following oral administration of the metal in the form of a carrier-free tracer and also as cadmium chloride. These 2 contrasting approaches (only the second being toxic) resulted in a similar retention pattern in the tissues. Both the cadmium burden and retention was greatest in the duodenum, followed by the kidney and the liver. This retention of cadmium in the duodenum following oral administration is relevant to the toxic effects of this metal associated with imparied calcium absorption in the intestine.

Administration, Oral↗

The autoradiographic localisation of retained orally administered cadmium tracer within Paneth cells of rat duodenum.

Rats not previously exposed to cadmium and rats whose sole source of drinking water for the previous 9 months contained 0.2 g/litre (200 ppm) cadmium were given 100 microCi Cd109 Cl2 by oral intubation. After 96 h more isotope was retained in the duodenums of rats not previously exposed to cadmium than in the duodenums of cadmium-exposed rats. Autoradiographic studies showed that in the rats not previously exposed to cadmium, radioactivity was concentrated in the Paneth cells at the base of the crypts of Lieberkuhn. This result did not occur in cadmium-exposed rats. Paneth cells are known to contain zinc and metallothionein but their retention of cadmium has not previously been reported. Since exposure to environmental cadmium is largely via contaminated food and water, the role of Paneth cells may be of significance in cadmium toxicology.

Administration, Oral↗

Electrical properties of a Na+-dependent phenylalanine transport in lizard (Lacerta galloti) duodenum.

The unidirectional transepithelial fluxes of L-phenylalanine across lizard duodenum were determined in flux chambers. Phenylalanine was preferentially transferred from the mucosal to the serosal fluid. This transport was accompanied by an accumulation of substrate from the mucosal medium into the tissue to a similar level and against a concentration gradient. There was no net movement of phenylalanine when the sodium was substituted by choline. The influx of L-phenylalanine into the epithelial cells of lizard duodenum was examined by incubating slices of intestine in radioactively-labelled solutions of the substrate for 2 min. The steady-state uptake was assessed after similar incubations lasting 45 min. Phenylalanine influx obeys the Michaelis-Menten equation with a Km of 5.1 and is dependent on the presence of sodium ions in the incubation medium. Phenylalanine has been used to induce changes in short-circuit current (delta Isc) across intestine. delta Isc was a hyperbolic function of amino acid concentration characterized by the parameters Jm (maximum change in delta Isc) and Km (concentration needed to attain an delta Isc equal to half the Jm). delta Isc determined Km constants showed good agreement with values obtained from direct measurements of phenylalanine uptake into tissue.

Animals↗

Transport of galactose and sodium across lizard duodenum.

Electrical parameters and transepithelial Na+ and galactose transport were determined in vitro across isolated duodenum of Lacerta galloti lizard. Electrical potential difference (PD) and short-circuit current (Isc) were dependent on the presence of Na+ in the bathing solutions. PD and Isc were affected by addition of galactose to the mucosal solution. Isotopic flux of Na+ measurements across short-circuited duodenum showed a net active Na+ absorption. The net flux of Na+ (JNa+net) accounted for the observed Isc. Both (JNa+net) and Isc were increased by the addition of galactose 5 mM to the mucosal solution. Isotopic flux galactose measurements in open-circuit conditions showed a net active galactose absorption. The net transport of galactose was decreased to zero in the absence of Na+ in mucosal and serosal reservoirs. Galactose has been used to induce changes in short-circuit current (delta Isc) across intestine. delta Isc was a hyperbolic function of galactose concentration characterized by the parameters Vmax (maximum change in delta Isc) and Km (concentration needed to attain a velocity equal to half the Vmax).

Animals↗

Cysteamine-induced duodenal ulcer: effects on calcium absorption across rat duodenum.

The effect of cysteamine-induced duodenal ulcers on calcium transport across rat duodenum was investigated. Intracellular calcium accumulation measured after 24 hr and 3 days of cysteamine injection showed a significant increase (P less than 0.001) in the duodenal strips isolated after 3 days with no change noticed in those isolated after 24 hr, although the morphological changes in both were very similar. The relationship between increasing calcium concentration in the incubation medium and intracellular calcium concentration is a saturable process that conforms to the Michaelis-Menten type of kinetics. The average maximal flux (Vmax) increased from 8.93 nmole/hr-gdw in normal to 12.5 nmole/hr-gdw in 3-day-ulcerated rats, with no apparent change in the Michaelis constant (Kt) (0.8 mM). Unidirectional influx of calcium across the mucosal membrane was significantly increased (P less than 0.001) in 3-day-ulcerated duodenum suggesting that the increase in calcium transport could be due to the activation of the active step at the mucosal border.

Animals↗

Histopathology of the duodenum and rumen of goats during experimental infections with Paramphistomum cervi.

On microscopic examination after experimental infection with Paramphistomum cervi, tissue reactions in the duodenum were more pronounced during early stages of the infection (20th day post-infection (DPI)). Immature parasites were seen migrating to the muscularis layer, and focal infiltration of macrophages and lymphocytes was observed in the lamina propria and in the interstitial tissue of Brunner's gland. At places, there was cystic dilatation of Brunner's gland. At 40 DPI, the parasite was not present in the duodenal sections, and cellular infiltration was more diffuse and consistent. With the passage of time, the tissue reactions and cellular infiltration in the duodenum became less pronounced, but at 80 days parasites were attached to the villi of the rumen. Infiltration of mononuclear cells in the supporting connective tissue of the rumen was also observed. Thus, it is concluded that the immature forms of Paramphistomum cervi caused more severe damage in the duodenal tissue, whereas the adult form inflicted mild tissue damage in the rumen of the experimental kids.

Animals↗

N-acetyltransferase activity in the quail (Coturnix coturnix jap) duodenum.

The activity and kinetics of N-acetyltransferase (NAT) in the quail duodenum were studied by radioenzymatic assay. NAT activity was highest when incubated under 37 degrees C, at pH 5.8 for 15 sec. Of the four substrates tested (tryptamine, 5,6-dihydroxytryptamine, serotonin, and N-acetylserotonin at concentrations of 0.08-4 mM), only tryptamine showed the substrate saturation phenomenon when incubated with the duodenal enzyme and acetyl-14C-coenzyme A. The saturation concentration of tryptamine was about 4 mM. Using the double reciprocal plot and regression equation, the Michaelis constant (Km) and maximal rate (Vmax) of NAT activity were found to be 0.204 mM and 0.917 nmol.mg protein-1.min-1, respectively. Diurnal study demonstrated higher NAT activity at middark (3.7 nmol.mg protein-1.min-1) and lower activity at midlight (2.4 nmol.mg protein-1.min-1), suggesting a circadian rhythm of the enzyme activities in the quail duodenum.

Animals↗

Dissociation of calcium- and barium-induced contractions of the rat duodenum smooth muscle.

The contractile responses elicited by calcium (Ca) and barium (Ba) upon the isolated rat duodenum immersed in a Ca-free Tyrode solution are not nervously mediated and are differently affected by epinephrine (E), cocaine (C) and verapamil (V). E antagonizes Ca but not Ba while C inhibits only Ba. The antagonism of V is greater towards Ba than Ca. The different influence of the drugs disappear in the excess potassium-depolarized duodenum. Thus, C and V block equally Ca and Ba, while E is only slightly effective against the two cations.

Animals↗

Motor activity of the rat duodenum in vivo: evidence for the existence of an atropine-resistant peristalsis.

The motor activity of the proximal duodenum has been investigated by means of a balloon method in urethane-anaesthetized rats. A series of atropine- (1 mg/kg i.v.) or hexamethonium- (20 mg/kg i.v.) sensitive rhythmic contractions can be demonstrated in the rat duodenum which represents a peristaltic reflex mediated by intramural cholinergic neurons. The atropine-sensitive peristaltic reflex is transiently suppressed by intravenous DMPP (0.1 mg/kg) GABA (3 mg/kg) or noradrenaline (10 micrograms/kg). In rats pretreated with guanethidine (20 mg/kg s.c.) plus naloxone (2 mg/kg i.v.) and theophylline (2 mg/kg i.v.) a second type of peristaltic reflex which is atropine-resistant but hexamethonium-sensitive can be demonstrated. These findings indicate that in the rat small intestine a peristaltic activity can be sustained by both atropine-sensitive and atropine-resistant mechanism, which may explain failure of atropine to affect intestinal motility in conscious rats.

Animals↗

The relaxing response of the isolated rat duodenum to nicotine.

1. The relaxing responses of the atropine-treated isolated rat duodenum to 12 microM nicotine (N) and transmural electrical stimulation (S) have been compared. 2. The effects of both N and S were unaffected by 3-30 microM guanethidine or previous reserpinization (1 mg/kg, i.p. during 5 days). 3. The effects of N and S were completely blocked by 0.5-2.0 mM procaine, 0.1 mM butacaine or 0.3-1.2 microM tetrodotoxin. 4. The relaxing response to N but not that to S was blocked by 0.3 mM hexamethonium or 3 microM mecamylamine and absent in the nicotine-desensitized preparation. 5. The effects of both N and S were unaffected in the adenosine-5'-triphosphate (ATP)-desensitized preparation. 6. It is suggested that the nonadrenergic and noncholinergic (NANC) relaxation of the rat duodenum in response to N and S is also nonpurinergic.

Adenosine Triphosphate↗