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Migrational responses of Hymenolepis diminuta to surgical alteration of gastro-intestinal secretions.

The effects of the direction of gut flow, of injections of glucose and saline into different regions of the small intestine and of surgical re-routing or ligature of gastric, biliary and pancreatic secretions into the small intestine have been correlated with changes in the migratory response of the rat tapeworm Hymenolepis diminuta. Reversing the normal anterior to distal flow of luminal contents in the small intestine did not affect worm migration following feeding. Injections of a glucose-saline solution into the duodenum did not initiate a migratory response; similar injections into the mid- and posterior regions of the small intestine resulted in migrational responses similar to those following intragastric glucose feeding. Re-routing gastric secretions to the distal duodenum inhibited anterior migration of the worms beyond the new point of entry of gastric juices. Results following re-routing and ligation of the biliary and pancreatic secretions suggest that there is a potent cue to anteriad migration in the pancreatic secretions. Biliary secretions also appear to contain an additional migratory cue to worm migration. In order of importance the factors stimulating/inhibiting worm migration are pancreatic greater than gastric greater than biliary greater than glucose. The results support the hypothesis that the factors affecting worm distribution in the small intestine are interactive and synergistic, involve other luminal factors, such as 5-hydroxytryptamine and the physico-chemical gradients, and are of a regional nature such that the migratory response of a particular worm is directly related to its position in the small intestine when the cues to relocation are received.

Animals↗

Effect of piperine, the active ingredient of black pepper, on intestinal secretion in mice.

We have investigated the effect piperine on castor oil-stimulated fluid accumulation in the mouse small intestine. Piperine (2.5-20 mg/kg, i.p.) dose-dependently reduced castor oil-induced intestinal fluid accumulation. The inhibitory effect of piperine (10 mg/kg i.p.) was strongly attenuated in capsaicin (75 mg/kg in total, s.c.)-treated mice but it was not modified by the vanilloid receptor antagonist capsazepine (30 mg/kg i.p.). Pretreatment of mice with hexamethonium (1 mg/kg i.p.), naloxone (2 mg/kg i.p.), yohimbine (1 mg/kg i.p.) or the cannabinoid CB(1) receptor antagonist SR141716A (0.3 mg/kg i.p.) did not modify the inhibitory effect of piperine (10 mg/kg i.p.). These results suggest that piperine reduces castor oil-induced fluid secretion with a mechanism involving capsaicin-sensitive neurons, but not capsazepine-sensitive vanilloid receptors.

Alkaloids↗

Intestinal secretion of erythromycin base.

Erythromycin fluxes into rabbit midjejunal segments were studied. When erythromycin was infused into the jugular vein of anesthetized rabbits, the antibiotic was secreted into the segments at a rate of 0.0136 +/- 0.0023 mg/min. Preloading of the segments with five and 20 times the plasma concentration did not diminish this secretion. Protein binding of the antibiotic within the lumen could not explain this secretion, since both ultrafiltration and chromatography of luminal solutions indicated that the biological activity was free erythromycin. Moreover, the transmural potential across the intestinal mucosa is likely to be theprincipal driving force, since greater than 80 mv would be required to sustain the observed secretion against an imposed 20-fold concentration difference between blood and lumen. The best explanation for the intestinal secretion of erythromycin appears to be an active transport pathway capable of concentrating erythromycin in the lumen. It is not clear what endogenous substances are transported by this pathway.

Animals↗

Mechanism of glucagon-induced intestinal secretion.

The effects of local intra-arterial glucagon infusion on transcapilary, lymphatic, and transmucosal fluid and protein fluxes were studied in autoperfused segments of cat ileum. The glucagon infusions resulted in a significant increase in intestinal blood flow, lymph flow, capillary filtration coefficient, capillary pressure, interstitial volume, and interstitial fluid pressure. Precapillary resistance and the pre-to-postcapillary resistance ratio decreased during the glucagon infusion. The transcapillary oncotic pressure gradient and the osmotic reflection coefficient were reduced, suggesting that capillary permeability is significantly increased with glucagon. Ultrastructural analysis of tissue samples acquired during the infusion of higher doses of glucagon indicates disruption of the mucosal membrane. An glucagon indicates disruption of the mucosal membrane. An alteration in mucosal structure is supported by the appearance of plasma proteins in the secreted fluid. The results of this study indicate that glucagon-induced intestinal secretion results from an alteration in capillary fluid balance, i.e., an increased capillary pressure and permeability.

Animals↗

The effect of calcium channel blockade on basal- and substance P-induced intestinal secretion.

Calcium plays a central role in modulating many physiologic events. We have investigated the role of calcium channel blockade in the control of basal (n = 6)- and substance P-stimulated (n = 6) intestinal transport in the isolated perfused rabbit ileum. Twenty-centimeter segments of ileum, harvested from New Zealand rabbits, were arterially perfused at 1.5 ml/min with an oxygenated modified Krebs buffer solution containing washed human red cells (Hct = 15-20%) and 2.5 mM Ca2+. The intestinal lumen was perfused at 2 ml/min with an isotonic solution containing 1.2 mM Ca2+ and [14C]PEG as a nonabsorbable volume marker. The infusion of verapamil (1 microgram/min) significantly reduced (P less than 0.05) the basal secretion of H2O, and Cl-. Verapamil prevented the secretory effect of substance P infused at 0.25 microgram/min. Intraarterial verapamil had no effect on vascular perfusion pressure. These data indicate that calcium channel blockade has significant effects on basal- and substance P-stimulated intestinal secretion and suggest that transmembrane calcium fluxes function as major determinants of basal- and secretagogue-stimulated intestinal transport.

Animals↗

The peptide YY-preferring receptor mediating inhibition of small intestinal secretion is a peripheral Y(2) receptor: pharmacological evidence and molecular cloning.

A peptide YY (PYY)-preferring receptor [PYY > neuropeptide Y (NPY)] was previously characterized in rat small intestinal crypt cells, where it mediates inhibition of fluid secretion. Here, we investigated the possible status of this receptor as a peripheral Y(2) receptor in rats. Typical Y(2) agonists (PYY(3-36), NPY(3-36), NPY(13-36), C2-NPY) and very short PYY analogs (N-alpha-Ac-PYY(22-36) and N-alpha-Ac-PYY(25-36)) acting at the intestinal PYY receptor were tested for their ability to inhibit the binding of (125)I-PYY to membranes of rat intestinal crypt cells and of CHO cells stably transfected with the rat hippocampal Y(2) receptor cDNA. Similar PYY preference was observed and all analogs exhibited comparable high affinity in both binding assays. The same held true for the specific Y(2) antagonist BIIE0246 with a K(i) value of 6.5 and 9.0 nM, respectively. BIIE0246 completely abolished the inhibition of cAMP production by PYY in crypt cells and transfected CHO cells. Moreover, the antagonist 1) considerably reversed the PYY-induced reduction of short-circuit current in rat jejunum mucosa in Ussing chamber and 2) completely abolished the antisecretory action of PYY on vasoactive intestinal peptide (VIP)-induced fluid secretion in rat jejunum in vivo. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) experiments showed that Y(2) receptor transcripts were present in intestinal crypt cells (3 x 10(2) molecules/100 ng RNA(T)) with no expression in villus cells, in complete agreement with the exclusive binding of PYY in crypt cells. Finally, a full-length Y(2) receptor was cloned by RT-PCR from rat intestinal crypt cells and also from human small intestine. We conclude that the so-called PYY-preferring receptor mediating inhibition of intestinal secretion is a peripheral Y(2) receptor.

Amino Acid Sequence↗