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N H Javed

Publications and source records attributed to N H Javed.

8 recordsLinked to original sources
PubMed2001

D-glucose releases 5-hydroxytryptamine from human BON cells as a model of enterochromaffin cells.

BACKGROUND & AIMS: 5-Hydroxytryptamine (5-HT) is released from enterochromaffin cells and activates neural reflex programs regulating motility and secretion. Although sugars are reported to release 5-HT in vivo, it is unclear whether they act directly on enterochromaffin cells or indirectly through an intermediary messenger. The aim was to determine if D-glucose is a stimulus for 5-HT release. METHODS: Human BON cells, derived from enterochromaffin cells, were treated with D-glucose, galactose, and the nonmetabolizable methyl alpha-D-glucopyranoside, or with fructose. RESULTS: Reverse-transcription polymerase chain reaction together with Western blot analysis revealed an SGLT-like protein. D-glucose caused a concentration-dependent increase in 5-HT release, which was mimicked by methyl alpha-D-glucopyranoside and galactose but not fructose. D-glucose-stimulated 5-HT release was significantly reduced by phloridzin. Concentrations of mannitol below 75 mmol/L were ineffective in releasing 5-HT. Brefeldin A abolished forskolin-stimulated 5-HT release without affecting basal or constitutive release. CONCLUSIONS: The results show that high concentrations of metabolizable and nonmetabolizable hexoses activate signal transduction pathways, leading to release of 5-HT. These findings imply a role for enterochromaffin cells as "glucose sensors" during ingestion of a meal.

Brefeldin A↗
PubMed2001

Mechanical stimulation activates Galphaq signaling pathways and 5-hydroxytryptamine release from human carcinoid BON cells.

5-Hydroxytryptamine (5-HT) released from enterochromaffin cells activates secretory and peristaltic reflexes necessary for lubrication and propulsion of intestinal luminal contents. The aim of this study was to identify mechanosensitive intracellular signaling pathways that regulate 5-HT release. Human carcinoid BON cells displayed 5-HT immunoreactivity associated with granules dispersed throughout the cells or at the borders. Mechanical stimulation by rotational shaking released 5-HT from BON cells or from guinea pig jejunum during neural blockade with tetrodotoxin. In streptolysin O-permeabilized cells, guanosine 5'-O- (2-thiodiphosphate) (GDP-beta-S) and a synthetic peptide derived from the COOH terminus of Galphaq abolished mechanically evoked 5-HT release, while the NH(2)-terminal peptide did not. An antisense phosphorothioated oligonucleotide targeted to a unique sequence of Galphaq abolished mechanically evoked 5-HT release and reduced Galphaq protein levels without affecting the expression of Galpha(11). Depletion and chelation of extracellular calcium did not alter mechanically evoked 5-HT release, whereas depletion of intracellular calcium stores by thapsigargin and chelation of intracellular calcium by 1,2-bis (o-Aminophenoxy) ethane-N,N,N',N'-tetraacetic acid tetra (acetoxymethyl) ester (BAPTA-AM) reduced 5-HT release. Mechanically evoked 5-HT release was inhibited by somatostatin-14 in a concentration-dependent manner. The results suggest that mechanical stimulation of enterochromaffin-derived BON cells directly or indirectly stimulates a G protein-coupled receptor that activates Galphaq, mobilizes intracellular calcium, and causes 5-HT release.

Bacterial Proteins↗
PubMed1995

Exquisite peptide specificity of oral tolerance in experimental autoimmune encephalomyelitis.

Experimental autoimmune encephalomyelitis (EAE), induced in Lewis rats by injection of myelin basic protein (MBP) and adjuvant, is a T cell-mediated autoimmune disease. Earlier studies from our laboratory have shown that oral administration of guinea pig MBP before encephalitogenic challenge induces T cell anergy and results in the suppression of clinical signs and CNS histopathologic changes of EAE. In contrast, oral administration of rat MBP did not confer a similar degree of protection. This study was undertaken to determine the tolerogenicity of the synthetic peptide 68-88 derived from guinea pig (GP) MBP and rat MBP. These peptides differ by a single amino acid at position 80. Lewis rats fed GP 68-88 were protected from EAE induced with GP 68-88 or rat 68-88. In contrast, feeding rats 68-88 did not protect the animals from challenge with either peptide. Measurement of the frequency of peptide-reactive Th1 cells showed results consistent with the clinical picture. The in vitro proliferative response was significantly suppressed following oral administration of either whole GP MBP, the GP peptide, or the rat peptide, irrespective of clinical status. These results extend our earlier observation at the whole molecule level that GP but not rat MBP confers oral tolerance. These findings suggest that small structural differences at the amino acid level can produce dramatic differences in clinical outcome, with important implications for the design of multiple sclerosis clinical trials.

Administration, Oral↗
PubMed1994

Enhanced tissue responsiveness in colonic ion transport of cow's milk-sensitized guinea pigs.

The effects of leukotriene D4 (LTD4) on ion transport were investigated in submucosa/mucosa colonic segments from guinea pigs sensitized to cow's milk and in age-matched, non-immune animals. Mediators released from mast cells in immune animals challenged with beta-lactoglobulin evoked an increase in short-circuit current that was reduced by SK&F 102922, a peptidoleukotriene antagonist. Serosal addition of LTD4 (0.15-1 microM) evoked a concentration-dependent, bumetanide-sensitive increase in short-circuit current which was greater in immune than non-immune controls. In the absence of ongoing neural activity, 1 microM LTD4 evoked an 8-20 microA/cm2 increase in short-circuit current which was increased 8-13-fold when ongoing neural activity was present. In tissues with ongoing activity, the response to 0.15 microM LTD4 was reduced by SK&F 102922, tetrodotoxin and atropine. LTD4 enhanced the responsiveness of the tissue to carbachol by a factor of two, but did not affect responses of T84 colonic epithelial cell monolayers to this agent. These results show enhanced secretory function for LTD4 in animals with allergy to cow's milk. They suggest that the level of ongoing neural activity in the enteric neural microcircuits is one of the major determinants of colonic secretory capacity.

Animals↗
PubMed1992

Acetylcholine release from colonic submucous neurons associated with chloride secretion in the guinea pig.

Electrical field stimulation of submucous neurons in the guinea pig distal colon evokes an increase in chloride secretion sensitive to cholinergic blockade. This study was undertaken in the guinea pig to determine the feasibility of measuring acetylcholine (ACh) release simultaneously with ion transport in sheets of colonic submucosa/mucosa set up in flux chambers modified for perfusion of the submucosal surface. Release of [3H]ACh was determined in the absence of cholinesterase inhibitors as the stimulus-evoked outflow of 3H from preparations preloaded with [3H]choline. [3H]ACh released in response to electrical stimulation correlated with short-circuit current at frequencies from 0.5 to 10 Hz. At 5 and 10 Hz, the stimulus-evoked release of [3H]ACh decreased during subsequent stimulation periods. The stimulus-evoked increase in [3H]ACh was attenuated by tetrodotoxin. [3H]ACh release evoked at stimulus frequencies of 0.5-10 Hz was not altered by atropine despite a reduction in short-circuit current. This study illustrates the feasibility of measuring ACh release simultaneously with ion transport in flux chambers. The results provide new information on the response characteristics of colonic submucous neurons and provide direct evidence for regulation of chloride secretion by ACh.

Acetylcholine↗
PubMed1992

Neuroimmune interactions: role for cholinergic neurons in intestinal anaphylaxis.

The role of cholinergic neurons in mediating chloride secretion in anaphylaxis was assessed in muscle-stripped segments of distal colon from guinea pigs immunized to bovine milk. beta-Lactoglobulin evoked a concentration-dependent increase in short-circuit current (Isc) in immune, but not nonimmune, tissues. The Isc response to beta-lactoglobulin was reduced by piroxicam, pyrilamine, and cimetidine. Tetrodotoxin and atropine reduced the Isc response to beta-lactoglobulin in immune animals, whereas mecamylamine and ICS 205-930 were ineffective. beta-Lactoglobulin evoked a concentration-dependent increase in acetylcholine (ACh) release in immune, but not nonimmune, animals. In immune tissues after challenge with beta-lactoglobulin, ACh release paralleled the change in Isc. Piroxicam, cimetidine plus pyrilamine, or a combination of piroxicam, cimetidine, and pyrilamine significantly reduced the release of ACh after beta-lactoglobulin challenge. Histamine, dimaprit, and prostaglandins E2 evoked an increase in ACh release. These results suggest that beta-lactoglobulin releases prostaglandins and histamine probably from mast cells. Secretory responses that occur when immune animals are challenged with beta-lactoglobulin result, in part, from activation of cholinergic neurons that utilize muscarinic synapses for transfer of signals to the epithelium.

Acetylcholine↗
PubMed1988

Standardization of different spirometers.

This study was designed to compare spirometers used for human testing and to determine whether the results obtained by different spirometers meeting the American Thoracic Society (ATS) requirements are interchangeable. Water-sealed spirometer (Harvard), dry bellow wedge spirometer (Vitalograph) and computerized pneumotachograph (Gould), all of them satisfying the ATS recommendations were compared. Forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), forced expired flow between 25 and 75% of FVC (FEF 25-75%) and 100 FEV1/FVC (FEV1%) were selected for comparative analysis. Measurements of these parameters were carried out on a total of 40 healthy volunteers of mixed nationalities. The Vitalograph values for FVC, FEV1 and FEV1% were significantly higher than those of the water-sealed spirometer (Harvard), but were closely similar to the values obtained by the Gould computerized pneumotachograph. Our results thus do not support the interchangeability of different spirometers and stress the importance of biological standardization of spirometers against each other.

Adult↗