The activity of phosphate-dependent glutaminase from the rat small intestine is modulated by ADP and is dependent on integrity of mitochondria

The effect of adenine nucleotides and phosphate on rat small intestine phosphate-dependent glutaminase (PDG) activity was investigated in intact mitochondria. Disruption of the integrity of mitochondria by sonication or freeze-thawing resulted in loss of enzyme activity. ADP was the strongest adenine nucleotide activator of the enzyme giving a V_max that was over 5-fold of that for AMP or ATP. The sigmoid activation curve of PDG by ADP became hyperbolic in presence ATP. ADP also lowered the K_m for glutamine and increased V_max and these effects were further enhanced by the presence of ATP. Activation of PDG by phosphate and ADP was not completely additive suggesting some antagonism between the activators. There was no clear relationship between changing ATP/ADP ratios and PDG activity in presence of a constant concentration of phosphate. However, ratios of approximately 1:4 and 4:1 gave the highest and lowest activities, respectively. The pH dependence of PDG activity was affected by phosphate concentration and results suggest that the divalent ion is the activating species.     

The role of visceral receptors in the mechanisms of neuroimmune interactions in mammalian small intestine

Exogenous administration of mast cell degranulation products into blood as well as their endogenous release induced by compound 48/80 or repeated egg albumin administration to sensitized rats proved to increase activity of mesenteric afferent nerve fibers in the small intestine. In addition, the primary contact with a foreign protein triggered a cascade of chemical processes mobilizing antioxidant systems and increasing nitric oxide production in the small intestinal tissues. Interleukin-1β or Escherichia coli lipopolysaccharide injections also had a long-term stimulating effect on intestinal receptors. Indometacin inhibited the effects induced by the bacterial endotoxin and interleukin-1β. The obtained data suggest that small intestinal interoceptors can monitor chemical environment and modulate body’s responses to foreign antigens. Interleukins-1β acts as a signal transmitter between immune cells and interoceptors, which is mediated by the production of secondary signal substances, in particular, prostaglandin E2 and histamine.     

The development of the small intestine

The remarkable degree of coordination between the development of various aspects of gastrointestinal function suggests that the process may be triggered by a single or a few central mechanisms, such as weaning and (or) hormones. Precocious development of enzyme and transport function can be induced by exogenous thyroxine and corticosteroids, while thyroidectomy and adrenalectomy abolish the normal pattern of postnatal development. These hormones may have a primary or a permissive role. Activation of the dormant hormonal mechanism could be controlled by a genetically coded biologic clock, such as chronologic age, or by a biological signal such as body size and oral intake. Generally speaking, shortly after birth, there are increases in the intestinal mucosal surface area, brush border membrane enzymes, and carrier-mediated transport. These adaptive changes occur as a result of the genetic endowment of the animal, but may be modified by environmental factors, particularly nutrient intake.     

The small intestine plays an important role in upregulating CGRP during sepsis

Although studies have indicated that calcitonin gene-related peptide (CGRP), a potent vasodilatory peptide, is upregulated after endotoxic shock, it remains controversial whether this peptide increases during sepsis and, if so, whether the gut is a significant source of CGRP under such conditions. To study this, polymicrobial sepsis was induced by cecal ligation and puncture (CLP) followed by fluid resuscitation. Plasma levels of CGRP were measured at 2, 5, and 10 h after CLP (i.e., early, hyperdynamic sepsis) and at 20 h after CLP (late, hypodynamic sepsis). The results indicate that plasma CGRP did not increase at 2--5 h but increased by 177% at 10 h after CLP (P < 0.05). At 20 h after the onset of sepsis, however, the elevated plasma CGRP returned to the sham level. To determine the source of the increased plasma CGRP, the liver, spleen, small intestine, lungs, and heart were harvested, and tissue CGRP was assayed at 10 h after CLP in additional animals. Only the small intestine showed a significant increase in tissue levels of CGRP (by 129%, P < 0.05). Determination of portal vs. systemic levels of CGRP indicates that portal CGRP was 65.7 +/- 22.7% higher than the systemic level at 10 h after CLP, whereas portal CGRP in sham-operated rats was only 4.9 +/- 2.1% higher. Immunohistochemistry examination revealed that CGRP-positive stainings increased in the intestinal tissue but not in the liver at 10 h after the onset of sepsis. The distribution of CGRP stainings was associated with intestinal nerve fibers. These results, taken together, demonstrate that upregulation of CGRP occurs transiently during the progression of sepsis (at the late phase of the hyperdynamic sepsis), and the gut appears to be a major source of such an increase in circulating levels of this peptide.     

The role of cernitins in cadmium effect on the absorption processes in rat small intestine

The effect of long-term intoxication of cadmium (administered subcutaneously in a dose of 1 mg Cd/kg of body weight once a week for one month) on the absorption of water, sodium, potassium, glucose, glycine and thiamine in the small intestine of rats was investigated. In addition, the influence of cernitins (special pollen extract) on the action of cadmium intoxication was tested. The cernitins were given by stomach pump in the form of an aqueous solution of Pollitabs Sport tablets in a dose of 1.5 mg of cernitin T-60 and 0.075 mg of cernitin GBX per individual twice a week for two weeks or four weeks according to the group of animals tested. The results indicated that long-term administration of cadmium increased the intestinal absorption of all tested substances. Meanwhile, the application of cernitins reduced the effects of cadmium intoxication upon intestinal absorption and the processes of absorption was close to normal.     

The role of the duodenum in adaptive changes in sucrose digestion in the small intestine of chicks

In two experimental series in situ applying perfusion technique, and in vitro, the role of the duodenum in adaptation of sucrose digestion was investigated in the proximal, medial and distal parts of the chick small intestine. No adaptive changes occurred in hydrolysis and carbohydrate transport if the pancreo-duodenal complex was isolated from the lower parts. It is suggested that on feeding with sucrose, factors arise in the duodenal mucosa causing adaptive changes in sucrase activity of the small intestine.     

The role of Ca2+ in the contractility of rabbit small intestine in vitro.

This study evaluated the role of Ca2+ in spontaneous and ACh- and KCl-induced contractions in longitudinal and circular smooth muscle from rabbit small intestine in vitro. In the first experiment, the amplitude, frequency and tone of spontaneous contractions in longitudinal and circular smooth muscle of small intestine were determined and, in the second experiment, the ACh- and KCl-induced responses of longitudinal and circular smooth muscle were measured. Atropine and guanethidine reduced the amplitude and tone of contractions in longitudinal and circular muscle, but reduced the frequency of contractions in circular muscle, only. TTX attenuated the amplitude of contractions and decreased the tone of contractions in longitudinal muscle, but increased the tone in circular muscle. Ca2+-free solutions, verapamil, nifedipine and caffeine diminished the three parameters of spontaneous contractions. Thapsigargin and cyclopiazonic acid increased the amplitude and tone of contractions in ileum longitudinal muscle, only, and cyclopiazonic acid increased the amplitude of contractions in circular muscle. Ca2+-free solutions, verapamil, nifedipine, thapsigargin, cyclopiazonic acid, and caffeine diminished ACh- and KCl-induced contractions. Those results suggest that extracellular Ca2+ plays a role in spontaneous contractions, and extracellular and intracellular Ca2+ participate in the ACh- and KCl-induced contractions of rabbit small intestine.     

The motoricity cycle of the small intestine

The electrical spike activity of the small intestine at the gastroduodenal junction occurs as migrating myoelectric complexes (MMCs), initiated regularly at intervals of 90-100 min. in the adult sheep and of 20-30 min. in the neonate. This ultradian rhythm, generated by the enteric nervous system, may become identical in the adult and in the neonate, by the use of methysergide which interacts with 5-HT myenteric neurones. The results suggest a postnatal development of a serotoninergic inhibitory system, involved in the control of the basic rest-activity cycle of the small intestine.     

Physiological role of glutaminase activity in Saccharomyces cerevisiae

The participation of glutaminase activity in glutamine degradation was studied in a wild-type strain (S288C) of Saccharomyces cerevisiae. Evidence is presented that this strain has two glutaminase activities, a readily extractable form (glutaminase B) and a membrane-bound enzyme (glutaminase A). Glutaminase A and B activities could also be distinguished by their thermostability, pyruvate sensitivity and pH optimum. Glutaminase B activity was negatively modulated by some 2-oxo acids, and in vivo pyruvate accumulation inhibited this activity. A mutant strain (CN10) with an altered glutaminase B activity was isolated and partially characterized. Its glutaminase B activity was more sensitive to inhibition by pyruvate and 2-oxoglutarate than the wild type, thus resulting in inactivation of this enzyme in vivo. The physiological role of glutaminase activity is discussed with regard to the phenotype shown by the mutant strain.     

Effects of starvation on the maximal activities of some glycolytic and citric acid-cycle enzymes and glutaminase in mucosa of the small intestine of the rat

Starvation decreases activities of some glycolytic and citric acid-cycle enzymes, and increases those of glucose 6-phosphatase and fructose bisphosphatase, whereas that of glutaminase is unchanged. These findings may be of significance for the control of glucose metabolism in the absorptive cells of the intestine.     

The role of bile and digestive juices in cadmium effect on the absorption processes in rat small intestine

The effects of bile and digestive juices was studied on the intestinal absorption of water, sodium and glucose in the small intestine of rats after their intoxication with one dose of cadmium 1.33 mg/kg of body weight injected intravenously. The investigations were carried out on 60 rats by the method of intestinal perfusion. The obtained results showed that cadmium inhibited the intestinal absorption of these substances. Bile and digestive juices abolished partially this effect during their physiological secretion. After administration of cholagogues no protective role of bile and digestive juices was observed alleviating the toxic effects of cadmium, and the intestinal absorption was even more reduced.     

The distribution of enterochromaffin cells in the human small intestine

Summary The distribution of argyrophile and argentaffin cells has been studied in the small intestine of five human adults. In proceeding cranio-caudally the characteristic feature of their distribution is the presence of eight to ten waves of rising and falling density. A progressive decrease in density of cells from duodenum to terminal ileum (described by previous workers) is not present.Re-examination of findings reported earlier in the small intestines of human foetuses shows that a predominant U shaped pattern of distribution is present in younger foetuses. This changes to the adult pattern by full term. The appearance of the adult pattern occurs earlier for argyrophile cells than for argentaffin cells.