Alpha and beta adrenoceptors mediate the inhibitory effect of epinephrine on the mucosal uptake of phenylalanine in the rat jejunum

Neurotensin (NT), a hormone released from intestine by ingested fat, facilitates lipid digestion by stimulating pancreatic secretion and slowing the movement of chyme. In addition, NT can contract the gall bladder and enhance the enterohepatic circulation (EHC) of bile acids to promote micelle formation. Our recent finding that NT enhanced and an NT antagonist inhibited [3H]taurocholate ([3H]TC) absorption from proximal rat small intestine indicated a role for endogenous NT in the regulation of EHC. Here, we postulate the involvement of intestinal mast cells in the TC uptake process and in the stimulatory effect of NT. In anesthetized rats with the bile duct cannulated for bile collection, infusion of NT (10 pmol·kg−1·min−1) enhanced the [3H]TC recovery rate from duodenojejunum by 2.2-fold. This response was abolished by pretreatment with mast cell stabilizers (cromoglycate, doxantrazole) and inhibitors of mast cell mediators (diphenhydramine, metergoline, zileuton). In contrast, mast cell degranulators (compound 48/80, substance P) and mast cell mediators (histamine, leukotriene C4) reproduced the effect of NT. NG-nitro-l-arginine methyl ester enhanced and l-arginine inhibited basal and NT-induced TC uptake, consistent with the known inhibitory effect of nitric oxide (NO) on mast cell reactivity. These results argue that basal and NT-stimulated TC uptake in rat jejunum are similarly dependent on mast cells, are largely mediated by release of mast cell mediators, and are subject to regulation by NO.

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Inhibitory effect of unconjugated bile acids on the intestinal transport of 5-methyltetrahydrofolate in rat jejunum in vitro.

Gut ◽

10.1136/gut.25.12.1376 ◽

1984 ◽

Vol 25 (12) ◽

pp. 1376-1379 ◽

Cited By ~ 5

Author(s):

H M Said ◽

D Hollander ◽

W B Strum

Keyword(s):

Bile Acids ◽

Intestinal Transport ◽

Inhibitory Effect ◽

Rat Jejunum

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Effects of indomethacin on energy metabolism in rat and human jejunal tissue in vitro

Clinical Science ◽

10.1042/cs1010493 ◽

2001 ◽

Vol 101 (5) ◽

pp. 493-498 ◽

Cited By ~ 10

Author(s):

Molly JACOB ◽

Ingvar BJARNASON ◽

Robert J. SIMPSON

Keyword(s):

Energy Metabolism ◽

Oxygen Uptake ◽

Energy Charge ◽

Lactate Production ◽

Inhibitory Effect ◽

Mitochondrial Morphology ◽

Rat Jejunum ◽

Drug Concentrations ◽

Inflammatory Drugs

Non-steroidal anti-inflammatory drugs (NSAIDs) are known to cause enteropathy, but the mechanism by which this toxicity occurs is less well established. This paper sets out to test the hypothesis that these drugs affect oxidative phosphorylation in jejunal tissue, thereby interfering with energy metabolism and rendering the tissue vulnerable to damage. Jejunal tissue obtained from rats and humans was used for in vitro determinations of oxygen uptake, lactate production and energy charge levels in the presence of indomethacin, a commonly used NSAID. In the rat jejunal tissue, drug concentrations of 0.5mM and 2.5mM produced significant decreases in oxygen uptake (P < 0.01) and energy charge levels in the tissue (P < 0.05). There was a corresponding increase in lactate production by the tissue at these indomethacin concentrations (P < 0.05). Rat jejunum examined by electron microscopy after incubation with various concentrations of indomethacin showed ultrastructural effects of the drug on mitochondrial morphology. In human tissue, an inhibitory effect of indomethacin on oxygen uptake was seen, but the effects on lactate production and energy charge were less conclusive. These findings suggest that indomethacin affects mitochondria and thereby impairs energy metabolism in jejunal tissue.

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Mechanism underlying the inhibitory effect of high calcium carbonate intake on iron bioavailability from ferrous sulphate in anaemic rats

British Journal Of Nutrition ◽

10.1079/bjn19960114 ◽

1996 ◽

Vol 75 (1) ◽

pp. 109-120 ◽

Cited By ~ 26

Author(s):

K. J. H. Wienk ◽

J. J. M. Marx ◽

A. G. Lemmens ◽

E. J. Brink ◽

R. Van Der Meer ◽

...

Keyword(s):

Ferrous Sulphate ◽

Basolateral Membrane ◽

Haemoglobin Concentration ◽

Inhibitory Effect ◽

Iron Bioavailability ◽

High Intake ◽

Proximal Half ◽

High Calcium ◽

Blood Haemoglobin ◽

Mucosal Uptake

The influence of high CaCO3, intake on the bioavailability of Fe from FeSO4, was assessed during Fe repletion of rats with Fe-deficiency-induced anaemia. Fe-deficient rats with a mean blood haemoglobin concentration of 4. 1 mmol/l were fed on purified Fe-adequate diets containing either 6.2 or 25.0g CaCO,/kg (ten rats per group). Haemoglobin repletion after 14 d was significantly depressed by high CaCO, intake (9.5 v. 9.8 mmol/l for high and low CaCO, intake respectively; P = 0·03), as was apparent Fe retention (367 v. 552 µg/d during days 5–7, P<0·001; 146 v. 196 µg/d during days 19–21, P < 0·001). The concentration of Fe in the liquid phase of the proximal half of the small intestine was significantly lower in the high-CaCO, group (3.71 v. 520 µg/g digesta; P = 0-02). Mucosal uptake and mucosal transfer of Fe were determined with orally administered59Fe and Cr as a non-absorbable marker. Mucosal transfer was significantly diminished by CaCO, loading (90 v. 100% of mucosal uptake; P = 0·04), whereas mucosal uptake was not.59Fe retention values at 14 d after administration were not significantly different (57.6 v. 51.9%; P = 0·14). Fe contents of liver and spleen were significantly decreased by high compared with low CaCO, intake (879 v. 590 pg Fe in liver, P < 0·001; 92 v. 63pg Fe in spleen, P <0·001). It is concluded that high intake of CaCO, depresses Fe bioavailability in rats. The CaCO,-induced decrease in Fe solubility in the digesta probably was associated with an increased efficiency of mucosal Fe uptake so that the amount of mucosal uptake remained unaltered. The CaCO,-induced decrease in Fe transfer through the mucosal cytoplasm and/or basolateral membrane may have been responsible for the concurrent decrease in Fe bioavailability.

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Inhibition of Na+-Pi cotransporter in small gut brush border by phosphonocarboxylic acids

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1987.252.2.g244 ◽

1987 ◽

Vol 252 (2) ◽

pp. G244-G249 ◽

Cited By ~ 7

Author(s):

M. Loghman-Adham ◽

M. Szczepanska-Konkel ◽

A. N. Yusufi ◽

M. Van Scoy ◽

T. P. Dousa

Keyword(s):

Intestinal Mucosa ◽

Brush Border ◽

Inhibitory Effect ◽

Small Intestinal Mucosa ◽

Rat Jejunum ◽

Phosphonoformic Acid ◽

Small Intestinal ◽

A Minor ◽

Phosphonocarboxylic Acids ◽

Chemical Analogue

We examined the effect of phosphonoformic acid (PFA) and phosphonoacetic acid (PAA) upon Na+-Pi cotransport in brush-border membrane (BBM) from small gut of rat. Both PFA and PAA inhibited the Na+ gradient-dependent uptake of 32Pi by BBM vesicles (BBMV) prepared from intestinal mucosa but had no effect on Na+-dependent uptakes of D-[3H]glucose, L-[3H]proline, or [14C]succinate. The uptake in the absence of Na+ gradient, or uptake at equilibrium period (180 min), was not affected by PFA or by PAA. A chemical analogue of PFA and PAA, phosphonopropionic acid, had only a minor inhibitory effect and phenylphosphonic acid was inactive. Neither PFA nor PAA influenced the activity of rat intestinal BBM alkaline phosphatase. The BBMV from rat jejunum had a much higher capacity for Na+ gradient-dependent uptake of 32Pi than BBMV from duodenum or ileum. The inhibition of BBMV 32Pi transport across rat jejunum by PFA is competitive. We suggest that PFA and PAA are specific inhibitors of Na+ gradient-dependent uptake of Pi by BBMV from small intestinal mucosa and that they could serve as useful experimental tools for the studies of intestinal Na+-Pi cotransport.

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