Ahmad Al-Saffar

Correlation between Peptide YY-Induced Myoelectric Activity and Transit of Small-Intestinal Contents in Rats

The effect of peptide YY (PYY) on the myoelectric activity of the small intestine was studied in relation to the transit of a 51Cr marker solution in fasted conscious rats. The myoelectric activity was recorded by means of bipolar electrodes implanted at 5, 20, and 35 cm from the pylorus. The marker was administered in the duodenum immediately after an activity front of a migrating myoelectric complex (MMC) had passed the first recording site. Under control conditions, the propagation of one activity front over the three recording levels was accompanied by the propulsion of 90.2 +/- 11.4% of the total radioactivity as one portion distal to the third electrode site. The median peak of the radioactivity was recovered at a distance approximately twice that propagated by an activity front. Intravenous infusion of PYY (50 pmol X kg-1 X min-1) had no effect on the occurrence of the MMC in the duodenum but interrupted its distal propagation and almost totally abolished the spiking activity in the jejunum. In comparison with controls, the transport of the marker was significantly retarded, and the median peak of the radioactivity was recovered proximal to the third electrode site. The results indicate that the small-intestinal contents are propelled as one portion in front of a propagating activity front. The inhibition of the activity front by PYY may account for the delay in the transit of the small-intestinal contents.(ABSTRACT TRUNCATED AT 250 WORDS)

Endotoxin actions on myoelectric activity, transit, and neuropeptides in the gut role of nitric oxide

The lipopolysaccharide (endotoxin) ofgram-negative bacteria has systemic effects in animalsand man. Our aim was to investigate the effects of E.coli lipopolysaccharide on motility and transit through the small intestine in rats and to analyzeplasma and tissue concentrations of intestinalneuropeptides. When lipopolysaccharide (20–160μg/kg) was administered intravenously, the migratingmyoelectric complex was replaced by spike burstsaccompanied by rapid transit. Tissue concentrations ofsubstance P and neurokinin A decreased, while plasmalevels of calcitonin gene-related peptide increased.Nω-Nitro-L-arginine, Nω-L-arginine methyl ester,dexamethasone, or indomethacin prevented these changesin myoelectric activity and tissue contents ofneuropeptides. All of these compounds, exceptindomethacin, prevented the increased rate of transit. Thus,lipopolysaccharide changes motility through the nitricoxide and arachidonic pathways, resulting in rapidtransit through the gut.

Reserpine-induced depletion of neuropeptide Y from cardiovascular nerves and adrenal gland due to enhanced release.

Summary1.The mechanisms underlying reserpine-induced depletion of neuropeptide Y-like immunoreactivity (NPY-LI) in relation to tissue content of noradrenaline (NA) and cardiovascular impairment were studied in guinea-pigs.2.Reserpine pretreatment (5 mg/kg SC) caused a 5-fold increase in plasma levels of NPY-LI with a maximum after 4 h. This was associated with a progressive fall in systemic arterial blood pressure and heart rate (to about 50% of basal values). The contents of NPY-LI and NA in nerves of the heart and quadriceps muscle were then reduced by about 75% and 85%, respectively. The adrenal content of NPY-LI was reduced by 40% 8 h after reserpine, while the adrenaline content was uninfluenced.3.Pretreatment with guanethidine depleted NA in the heart but did not influence plasma levels or tissue content of NPY-LI per se. The reserpine-induced increase in plasma NPY-LI and the depletion of NPY-LI in the heart and skeletal muscle was to a large extent prevented by guanethidine. The reserpine-induced bradycardia and hypotension were reduced after guanethidine pretreatment.4.Chlorisondamine pretreatment depressed heart rate, blood pressure and plasma levels of NPY-LI. Furthermore, chlorisondamine inhibited the reserpine-induced increase in plasma NPY-LI and prevented the reduction in tissue content of NPY-LI in the heart, skeletal muscle and adrenal. The tissue depletion of NA induced by reserpine, however, was not influenced by chlorisondamine. The reserpine-induced hypotension was reduced by chlorisondamine, while the bradycardia was not influenced.5.In conclusion, reserpine pretreatment induced a marked increase in plasma NPY-LI in guinea-pigs. The plasma raise in NPY-LI was reduced by guanethidine, which is likely to inhibit NPY release from sympathetic terminals, and blocked by chlorisondamine which blocks sympathetic transmission at the ganglionic level, suggesting that reserpine caused an enhanced release of NPY from certain sympathetic nerves and adrenal gland. Enhanced release of NPY in excess of resupply caused by neurogenic activation and/or loss of local presynaptic inhibitory control of release due to NA depletion may therefore explain the reduction in tissue content of NPY-LI. Whether NPY depletion contributes to the cardiovascular impairment seen after reserpine remains of be established.

Analysis of the control of intestinal motility in fasted rats, with special reference to neurotensin.

Migrating myoelectric complexes (MMC) in the small intestine of fasted rats were monitored by means of four bipolar electrodes chronically implanted at 5, 15, 25, and 35 cm distal to the pylorus. In intact rats the MMC occurred at regular intervals. Truncal abdominal vagotomy did not influence the initiation and propagation of the MMC. Administration of atropine, hexamethonium, or somatostatin significantly decreased the spiking activity of the MMC by 30-45% in the duodenum and jejunum. Infusion of neurotensin at two different doses (3.6 or 7 pmol X kg-1 X min-1) interrupted the activity front of the MMC and induced irregular spiking activity at all recording levels in control rats. In vagotomized rats neurotensin interrupted the activity front inconsistently. After atropine or hexamethonium administration, infusion of neurotensin did not interrupt the distal propagation of the activity front in the jejunum. Guanethidine, naloxone, cimetidine, mepyramine, haloperidol, and a substance P antagonist did not change the MMC or alter the normal response to neurotensin. The results suggest that the inhibitory effect of neurotensin on the propagation of the jejunal activity front involves activation of enteric cholinergic mechanisms. Neurotensin seems to induce irregular spiking activity by a direct myogenic action. The enteric cholinergic innervation of the small intestine partially contributes to the occurrence of the spiking activity of the MMC in fasted rats.

Influence of Fasting and Bombesin-Induced Myoelectric Activity on the Transit of Small-Intestinal Contents in the Rat

The relation between the occurrence of the migrating myoelectric complexes (MMC) and the transit of small-intestinal contents was studied in fasted, conscious rats. MMC were monitored by means of three bipolar electrodes implanted along the small intestine 5, 20, and 35 cm distal to the pylorus. In the presence of an MMC, the radioactive marker was transported along the small intestine as one main peak and recovered aboral to the activity front. Intravenous infusion of bombesin, 3 pmol X kg-1 X min-1, disrupted the MMC and induced irregular spiking activity at all recording levels. Furthermore, during bombesin infusion the radioactive marker was propelled a considerable distance, although the transit was significantly retarded in comparison to that in the presence of an MMC (p less than 0.01). The results indicate that the small-intestinal contents are propelled aboral to an activity front. Continuous irregular spiking activity during bombesin infusion contributes less to the transit of the small-intestinal contents than the activity front of MMC observed during fasting.

Somatostatin inhibits bombesin-induced effects on migrating myoelectric complexes in the small intestine of the rat

The effect of i.v. infusions of bombesin and somatostatin, administered either separately or in combination, on migrating myoelectric complexes (MMCs) in the small intestine were studied in conscious, fasted rats. The myoelectrical activity was recorded by means of three bipolar electrodes chronically implanted into the duodenum and jejunum. Infusion of bombesin (0.5, 0.9 and 3 pmol . kg-1 . min-1) interrupted the MMC and induced irregular spiking activity similar to that observed on feeding. Only after the highest dose a consistent inhibition of the MMCs and a significant increase (P less than 0.05) of the spiking activity were achieved at all recording levels. Somatostatin (90 pmol . kg-1 . min-1) did not interrupt the MMC, but reduced significantly the incidence of the activity fronts and spiking activity of the MMCs (P less than 0.05). The effects of bombesin (3 pmol . kg-1 . min-1) on the MMC pattern were inhibited by simultaneous infusion of somatostatin (P less than 0.05). In a second series of experiments, using anesthetized rats, infusion of bombesin (0.5 and 3 pmol . kg-1 . min-1) increased the plasma concentration of neurotensin- gastrin-like immunoreactivities in a dose-dependent manner. The results show that bombesin alters the myoelectrical activity of the small intestine from a fasting to a fed pattern. Since the effect of bombesin was inhibited by the hormone release inhibitor somatostatin, it is suggested that the effect of bombesin on MMC may be secondary to the release of gastrointestinal peptides, such as neurotensin or gastrin.

INFLUENCE OF THE NERVOUS SYSTEM ON THE ACTION OF NEUROTENSIN IN THE SMALL INTESTINE OF RATS

We have reported recently that i.v. infusion of neurotensin (NT) replaces the small intestinal migrating myoelectrical complexes (MMCs), in the small intestine of fasted rats, by irregular spiking activity.’ The motility pattern induced by neurotensin resembles that seen after ingestion of food. In contrast to the effects of neurotensin, several COOHand NH,-fragments of neurotensin do not convert the fasting pattern of the myoelectrical activity, indicating that the effect is produced by the intact neurotensin sequence rather than by small fragments of neurotensin. In the present experiments, the importance of the innervation of the intestine for the effects of NT on the MMCs has been analyzed by means of vagotomy and cholinergic and adrenergic blocking agents.