Gastrointestinal Tract In Response Research Articles

Molecular regulation of transferrin receptor and ferritin expression in the rat gastrointestinal tract

BACKGROUND & AIMS: The role of the transferrin receptor and ferritin i n the regulation of intestinal dietary iron uptake and excretion is unknown. This study aimed to determine the regulation of transferrin receptor and ferritin messenger RNA (mRNA) in the rat gastrointestinal tract in response to dietary iron changes. METHODS: In situ hybridization studies for transferrin receptor and L-ferritin mRNAs were performed using tissues from normal-iron-deficient, and iron- loaded rats. RESULTS: L-ferritin mRNA was localized to small intestinal crypt and villus epithelial cells and colonic crypt and surface epithelial cells with mRNA levels up-regulated in iron-loaded rats. Transferrin receptor mRNA was detected in crypt epithelial cells of the small and large intestine in iron-deficient and normal rats. In contrast, in iron-loaded rats, transferrin receptor mRNA was also detected in the superficial epithelial cells of the small intestine and colon, which contained increased stores of iron. Transferrin receptor mRNA levels were increased in the colon. CONCLUSIONS: In the iron- deficient and normal rat intestine, transferrin receptor mRNA was expressed only by proliferating crypt epithelial cells. In iron-loaded rats, however, surface enterocytes of the intestine expressed both transferrin receptor mRNA and increased ferritin mRNA levels. (Gastroenterology 1996 Mar;110(3):790-800)

Influence of a meal and incremental doses of zinc on changes in zinc absorption

The objective of this study was to determine the effect of increasing quantities of zinc, administered with and without a meal, on zinc absorption. Fractional absorption of incremental quantities of zinc in four normal adults was determined by measuring fecal excretion of unabsorbed isotope on 3 consecutive days by using three different stable isotopes of zinc (67Zn, 68Zn, and 70Zn). Isotopes were administered in the post-absorptive state and, on a subsequent occasion, with a standard zinc-free breakfast. In the postabsorptive state, fractional absorption was not affected by the quantity of zinc ingested until this exceeded 5 mg. When the zinc was administered with a meal, however, fractional absorption of 3 and 5 mg was less than for 1 mg. These results are compatible with the hypothesis that exogenous dietary zinc has to compete for absorption with endogenous zinc that has been secreted into the lumen of the gastrointestinal tract in response to a meal.

Cholecystokinin (CCK)-induced stimulation of luteinizing hormone (LH) secretion in adult male rhesus monkeys: examination of the role of CCK in nutritional regulation of LH secretion

Studies were performed with the overall goal of testing the hypothesis that cholecystokinin (CCK), a peptide hormone released from the gastrointestinal tract in response to meal consumption, provides a metabolic signal which modulates LH secretion in response to changes in the body's nutritional intake. In an initial study to document the effects of CCK on LH secretion in adult male rhesus monkeys, sulfated CCK-8 (7 and 15 micrograms/kg) was administered to six monkeys, and blood samples were collected from indwelling venous catheters. The 15-micrograms/kg dose of CCK elicited a rapid release of LH, with peak LH levels of 31.29 +/- 7.19 ng/ml occurring within 5-15 min. To determine the CCK receptor type mediating the effect of CCK on LH secretion, specific CCK type-A (L-364,718) and type-B (L-365,260) receptor antagonists (1 mg/kg) were administered to five monkeys 15 min before CCK administration. The CCK-A antagonist completely blocked LH secretion in response to CCK, whereas the CCK-B antagonist had no effect. To assess whether endogenous CCK, released in response to food intake, stimulates LH secretion, six monkeys were fasted for 1 day and then provided with a normal meal of monkey chow (i.e. a refeed meal) the following day, with either no antagonist, CCK-A antagonist, or CCK-B antagonist administered 30 min before the meal. As previously demonstrated, meal consumption after a brief period of fasting caused a rapid stimulation of pulsatile LH secretion. The refeed meal led to a comparable stimulation of LH secretion regardless of whether monkeys received no antagonist (3.7 +/- 0.44 LH pulses/9 h), CCK-A antagonist (3.33 +/- 0.56 LH pulses/9 h), or CCK-B antagonist (4.0 +/- 0.78 LH pulses/9 h). These results indicate that CCK can stimulate LH secretion in adult male rhesus monkeys, acting via type-A CCK receptors. However, endogenous CCK released in response to meal intake does not appear to be responsible for the meal-induced stimulation of LH secretion that occurs when monkeys are fed a normal meal after a brief period of fasting.

Cholecystokinin (CCK)-induced stimulation of luteinizing hormone (LH) secretion in adult male rhesus monkeys: examination of the role of CCK in nutritional regulation of LH secretion.

Studies were performed with the overall goal of testing the hypothesis that cholecystokinin (CCK), a peptide hormone released from the gastrointestinal tract in response to meal consumption, provides a metabolic signal which modulates LH secretion in response to changes in the body's nutritional intake. In an initial study to document the effects of CCK on LH secretion in adult male rhesus monkeys, sulfated CCK-8 (7 and 15 micrograms/kg) was administered to six monkeys, and blood samples were collected from indwelling venous catheters. The 15-micrograms/kg dose of CCK elicited a rapid release of LH, with peak LH levels of 31.29 +/- 7.19 ng/ml occurring within 5-15 min. To determine the CCK receptor type mediating the effect of CCK on LH secretion, specific CCK type-A (L-364,718) and type-B (L-365,260) receptor antagonists (1 mg/kg) were administered to five monkeys 15 min before CCK administration. The CCK-A antagonist completely blocked LH secretion in response to CCK, whereas the CCK-B antagonist had no effect. To assess whether endogenous CCK, released in response to food intake, stimulates LH secretion, six monkeys were fasted for 1 day and then provided with a normal meal of monkey chow (i.e. a refeed meal) the following day, with either no antagonist, CCK-A antagonist, or CCK-B antagonist administered 30 min before the meal. As previously demonstrated, meal consumption after a brief period of fasting caused a rapid stimulation of pulsatile LH secretion. The refeed meal led to a comparable stimulation of LH secretion regardless of whether monkeys received no antagonist (3.7 +/- 0.44 LH pulses/9 h), CCK-A antagonist (3.33 +/- 0.56 LH pulses/9 h), or CCK-B antagonist (4.0 +/- 0.78 LH pulses/9 h). These results indicate that CCK can stimulate LH secretion in adult male rhesus monkeys, acting via type-A CCK receptors. However, endogenous CCK released in response to meal intake does not appear to be responsible for the meal-induced stimulation of LH secretion that occurs when monkeys are fed a normal meal after a brief period of fasting.

Effect of Necrotizing Enterocolitis on Urinary Epidermal Growth Factor Levels

The pattern of urinary epidermal growth factor/creatinine levels in necrotizing enterocolitis was examined in 75 infants (in 28 infants the diagnosis of necrotizing enterocolitis was considered; 47 infants were studied for effect of surgery or nutrition on epidermal growth factor levels). There was a consistent and significant increase in epidermal growth factor/creatinine values at the time of diagnosis of necrotizing enterocolitis compared with baseline values. Epidermal growth factor levels in infants without necrotizing enterocolitis and in early nutrition remained unchanged. These results suggested that urinary epidermal growth factor/creatinine levels may differentiate stage II and III necrotizing enterocolitis from stage I disease. The increased epidermal growth factor/creatinine levels may be related to the absorption into the circulation of preexisting gastrointestinal tract epidermal growth factor through damaged tissue or to increased synthesis by the gastrointestinal tract in response to the injury caused by necrotizing enterocolitis.

Effect of thermal injury and immunosuppression on the dissemination of Candida albicans from the mouse gastrointestinal tract.

Candida albicans dissemination through the gastrointestinal tract was examined in mice given a thermal injury, immunosuppressive therapy, or both. After gastrointestinal tract colonization with C. albicans, mice were initially subjected to a 20% total body surface area, full-thickness, dorsal scald burn. Only one mouse in the burned group (5%) had evidence of C. albicans in the liver at the time the mice were killed. No dissemination was observed in sham-burned animals. When mice were immunosuppressed with cyclophosphamide, an increased incidence of gastrointestinal tract dissemination was noted in burned (31%) and sham-burned (23%) mice; however, only 3 days after burn was there a significant difference in dissemination between burned and sham-burned mice (p less than 0.02). This corresponded to the day of severest neutropenia in response to cyclophosphamide treatment. The results of the study indicate that C. albicans can disseminate from the gastrointestinal tract in response to thermal injury, but a significant suppression of the immune response must occur for the event to be commonplace.

Effects of autonomic stimulation on the release of vasoactive intestinal peptide from the gastrointestinal tract in the calf.

1. The effects of autonomic stimulation on the release of vasoactive intestinal peptide (VIP) from the gastrointestinal tract have been investigated in adrenalectomized claves 2-5 weeks after birth.2. Stimulation of the peripheral ends of the splanchnic nerves (10 Hz for 10 min) caused a small fall in the concentration of VIP in portal and arterial plasma, together with a rise in the concentration in intestinal lymph. None of these changes achieved statistical significance.3. The effects of stimulation of the peripheral ends of the thoracic vagi, below the heart (10 Hz for 10 min), were found to depend in part upon the integrity of the splanchnic sympathetic innervation. A substantial rise in the concentration of VIP in intestinal lymph occurred whether or not the splanchnic nerves had been cut whereas an associated rise in arterial plasma VIP was only observed in calves in which the splanchnic nerves had been sectioned.4. The rise in the concentration of VIP in intestinal lymph, in response to vagal stimulation, was unaffected by concomitant stimulation of the splanchnic nerves, although the associated rise in arterial plasma VIP concentrations was suppressed. The response was also found to be resistant to atropine.5. The minimum estimated concentration of VIP in the extracellular fluid of the gastrointestinal tract was estimated to be about 60 p-mole/l. at rest and to rise by 70-120 p-mole/l. in response to vagal stimulation.6. Intravenous infusions of VIP at a dose of 50 ng kg(-1) min(-1) (16 p-mole kg(-1) min(-1)), which raised the minimum estimated concentration of VIP in the gastro-intestinal tract to the highest range encountered during stimulation, produced no significant changes in the concentrations of glucose, insulin, pancreatic glucagon or pancreatic polypeptide in the arterial plasma.7. It is concluded that a small amount of VIP is released from the gastrointestinal tract in response to vagal stimulation. In contrast, release of VIP is unaffected by stimulation of the splanchnic nerves except in so far as the rate at which the peptide passes into the circulation is reduced by adrenergic vasoconstriction.

Influence of the autonomic nervous system on the release of vasoactive intestinal polypeptide from the porcine gastrointestinal tract.

1. The release of vasoactive intestinal polypeptide from the gastrointestinal tract in response to stimulation of the vagus nerves, the splanchnic nerves and to intra-arterial infusion of acetylcholine (ACh) was examined in pigs. 2. Stimulation of the vagus nerves caused an abrupt increase in the release of vasoactive intestinal polypeptide. The amount of the peptide released depended on the frequency at which the nerves were stimulated. Maximum release was obtained at 8 Hz. 3. Atropine and beta-adrenergic blocking agents failed to diminish the vagally induced release of vasoactive intestinal polypeptide, while the response was completely blocked by hexamethonium and increased after alpha-adrenergic blockade and after splanchnicotomy. 4. Intra-arterial infusion of ACh closely imitated the response to vagal stimulation, but the release of vasoactive intestinal polypeptide induced by ACh was abolished by atropine. 5. Stimulation of the splanchnic nerves caused a decrease in the release of vasoactive intestinal polypeptide, an action which was annulled by alpha-adrenergic blockade, but still present after the adrenal glands were isolated from the circulation. The inhibitory effect of splanchnic stimulation significantly diminished the vagally induced release of vasoactive intestinal polypeptide. 6. The results demonstrate a dual innervation with opposing effects on the neurones containing vasoactive intestinal polypeptides. The possible physiologic implication of this finding is discussed.

A humoral reticuloendothelial-depressing substance in shock.

The granulopectic activity of the reticuloendothelial system was assessed by measuring the clearance of carbon particles from the blood of splenectomized, normotensive "assay" dogs. When such animals were cross transfused with portal venous blood from splenectomized, normotensive "experimental" animals, there was a small decline (K1 – K2 = 0.0060) in the phagocytic index. However, when experimental dogs were subjected to hemorrhagic hypotension (mean arterial pressure of 40 mm Hg for 90 min), cross transfusion of portal venous blood to the assay animal resulted in a very marked ( P < 0.001) depression in phagocytic activity (K1 – K2 = 0.0218). On the other hand, cross transfusion of femoral artery blood from experimental dogs subjected to hemorrhagic hypotension caused only a slight decline in the phagocytic index of the assay animals (K1 – K2 = 0.0051). The results strongly suggest that a humoral reticuloendothelial-depressing substance is present in the portal venous blood, but not in the femoral arterial blood, of dogs subjected to hemorrhagic hypotension. This substance is probably formed in the gastrointestinal tract in response to hypotension.