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Biomedical subjects

M Field

Publications and source records attributed to M Field.

At least 181 records · Page 10Linked to original sources
PubMed1980

In vitro antisecretory effects of trifluoperazine and other neuroleptics in rabbit and human small intestine.

The inhibitory effects of several neuroleptic agents on intestinal secretion were examined in vitro by measuring short-circuit current, net Cl flux, and cyclic nucleotide concentration, In rabbit ileal mu cosa, trifluoperazine (0.2-0.5 mM) did not significantly alter basal transport rates, but partially inhibited responses to the following secretagogues: theophylline, 8-Br-cAMP, VIP, dimethyl-PGE2 and heat-stable Escherichia coli enterotoxin (a cGMP agonist). Trifluoperazine completely inhibited the response to Ca ionophore A23187. In human small intestinal mucosa, trifluoperazine (0.1-0.5 mM) inhibited electrical responses to VIP and theophylline almost completely. The inhibitory action of trifluoperazine was manifest only on serosal addition. Trifluoperazine did not significantly alter cAMP or cGMP concentrations either under basal conditions or in the presence of secretagogues. It also did not diminish the electrical response to luminally added D-glucose. Three other neuroleptics were tested and found to have antisecretory action; the order of potencies were trifluoperazine greater than chlorpromazine greater than haloperidol greater chlorprothixene. Since all four agents are potent inhibitors of calcium-dependent regulator in bovine brain, this ubiquitous protein may also be the target for their antisecretory action in intestine.

16,16-Dimethylprostaglandin E2↗
PubMed1979

Coupled sodium-chloride influx across brush border of flounder intestine.

Measurements of the unidirectional influxes of Na and Cl from the mucosal solution into the epithelium (Jme) of flounder intestine under short-circuit conditions reveal the presence of a coupled NaCl influx process at the brush border membrane which appears to be essential for the absorption of these ions. JClme and JName were inhibited by replacing Na or Cl, respectively, in the bathing media with non-transported ions which also reduced the short-circuit current (Isc) to near-zero values. Addition of furosemide to the mucosal solution alone inhibited the Isc and reduced JClme and JName under control conditions, but not in the absence of Na or Cl, respectively. The reductions in JClme and JName elicited by ion replacement or furosemide were approximately equal, suggesting that the coupled influx mechanism mediates a one-for-one entry of these ions into the cell from the mucosal solution. Furosemide inhibited Cl absorption by reducing the unidirectional Cl flux from mucosa to serosa, consistent with its inhibition of the influx process. As in other epithelia, coupled NaCl influx is inhibited by cyclic AMP, which accounts for the decrease in Cl absorption elicited by cyclic nucleotides. These results support the notion that transcellular NaCl transport is a neutrla process and that the serosa-negative transepithelial electrical potential difference and preponderance of Cl over Na absorption under short-circuit conditions result from dissimilar permeabilities of the paracellular pathway to Na and Cl.

Animals↗
PubMed1979

Mechanisms of action of cholera and Escherichia coli enterotoxins.

Current information is reviewed on the mechanism of secretion in small intestine, including how it is altered by cyclic 3',5'-adenosine monophosphate and on the structures and properties of cholera and both heat-labile and heat-stable Escherichia coli enterotoxins. Two separate active ion transport processes are altered by cyclic 3',5'-adenosine monophosphate: 1) coupled absorption of NaCl is inhibited in villus cells and 2) active anion secretion is stimulated, probably in crypt cells. Cholera and heat-labile E. coli toxins exert their secretory effect by stimulating intestinal mucosal adenylate cyclase. This stimulation results from the A1 subunit catalyzed transfer of adenosine diphosphate ribose from NAD to a membrane-bound guanosine triphosphatase, thereby inhibiting the enzyme, which normally represses adenylate cyclase. Heat-stable E. coli enterotoxin stimulates intestinal mucosal guanylate cyclase, which appears to be the basis for its enterotoxicity.

Animals↗
PubMed1979

Effects of heat-stable enterotoxin of Yersinia enterocolitica on ion transport and cyclic guanosine 3',5'-monophosphate metabolism in rabbit ileum.

Strains of Yersinia enterocolitica produce a heat-stable enterotoxin which is positive in the suckling mouse bioassay. Partial purification by a procedure previously worked out for heat-stable Escherichia coli enterotoxin yielded a substance which increases particulate guanylate cyclase activity and short-circuit current and inhibits active Cl-absorption in rabbit ileal mucosa. These effects of Y. enterocolitica enterotoxin are similar to those of heat-stable E. coli enterotoxin, suggesting a common mechanism of action.

Animals↗
PubMed1979

Sodium-coupled chloride transport by epithelial tissues.

There is compelling evidence that active Cl absorption by a variety of epithelia, widely distributed throughout the animal kingdom, is the result of an electrically neutral Na-coupled transport process at the luminal membrane and that the energy for transcellular Cl movement is derived from the Na gradient across that barrier. These co-transport processes are found predominantly in "leaky" or "moderately leaky" epithelia and permit these tissues to absorb Na and Cl with high degrees of efficacy. In addition, there is a growing body of evidence that cyclic AMP and Ca-induced electrogenic Cl secretion by a wide variety of epithelia may involve electrically neutral, Na-coupled Cl entry across the contraluminal membrane and that the energy for these secretory processes is derived from the Na-gradient across that barrier. A model for electrogenic Cl secretion that accounts for the available data is presented.

Absorption↗
PubMed1978

Ion transport across the isolated intestinal mucosa of the winter flounder, Pseudopleuronectes americanus. I. Functional and structural properties of cellular and paracellular pathways for Na and Cl.

The isolated intestinal mucosa of the flounder, Pseudopleuronectes americanus, when bathed in a 20 mM HCO3-Ringer's solution bubbled with 1% CO2 in O2, generated a serosa-negative PD and, when short-circuited, absorbed Cl at almost 3 times the rate of Na. Reducing HCO3 to 5 mM decreased the net Cl flux by more than 60%. The following results suggest that, despite the PD, Na and Cl transport processes are nonelectrically coupled: replacing all Na with choline abolished both the PD and net Cl flux; replacing all Cl with SO4 and mannitol abolished the PD and the net Na flux; and adding ouabain (to 0.5 mM) abolished the PD and the net Cl flux. Nearly all of the unidirectional serosa-to-mucosa Cl flux (JClsm) seemed to be paracellular since it varied with PD and Cl concentration in a manner consistent with simple diffusion. JClsm was only about one-fourth of JNasm, suggesting that the paracellular pathway is highly cation-selective. The data can be explained by the following model: (i) Na and Cl uptake across the brush border are coupled 1 : 1; Na is pumped into the lateral space and Cl follows passively, elevating the salt concentration there; (ii) the tight junction is permeable to Na but relatively impermeable to Cl; and (iii) resistance to Na diffusion is greater in the lateral space (considered in its entirety) than in the tight junction. If these assumptions are correct, the serosa-negative transmural PD is due mainly to a salt diffusion potential across the tight junction and, under short-circuit condition, most of the Na pumped into the lateral space diffuses back into the luminal solution, whereas most of the Cl enters the serosal solution. Morphological features of the epithelium support this interpretation: the cells are unusually long (60 micrometer); there is little distension of the apical 12 micrometer of the lateral space during active fluid absorption; and distension distal to this region is intermittently constricted by desmosomes.

Animals↗
PubMed1978

Heat-stable enterotoxin of Escherichia coli: in vitro effects on guanylate cyclase activity, cyclic GMP concentration, and ion transport in small intestine.

A partially purified preparation of the heat-stable enterotoxin of Escherichia coli caused a rapid and persistent increase in electric potential difference and short-circuit current when added in vitro to the luminal surface of isolated rabbit ileal mucosa. As little as 1 ng/ml produced an easily detectable response. Under short-circuit condition, the enterotoxin abolished net Cl- absorption; this change was half that produced by theophylline, which stimulated net secretion. The enterotoxin did not change cyclic AMP concentration but caused large and persistent increases in cyclic GMP concentration. The electrical and nucleotide responses exhibited similar and unusually broad concentration-dependences and maximal effects could not be demonstrated. Theophylline elevated cyclic GMP concentration 3-fold both in the presence and absense of the enterotoxin, suggesting no effect of the toxin on cyclic GMP phosphodiesterase. Guanylate cyclase [GTP pyrophosphatelyase(cyclizing); EC 4.6.1.2] activity in a crude membrane fraction from intestinal epithelial cells was stimulated 7-fold by the enterotoxin. These results suggest that guanylate cyclase stimulation is the basis for the toxin's diarrheagenic effect.

Bacterial Toxins↗
PubMed1978

Isolation of nontoxinogenic mutants of Vibrio cholerae in a colorimetric assay for cholera toxin using the S49 mouse lymphosarcoma cell line.

A mouse lymphosarcoma (S49) cell line that is growth-inhibited by agents that elevate intracellular concentrations of adenosine 3':5'-cyclic phosphate was used in a sensitive and convenient colorimetric assay for cholera toxin. S49 cells suspended in Dulbecco's modified Eagle's minimal essential medium containing 10(-5)--10(-6) M RO 20-1724, an analogue of 4-(3,4-demethoxybenzyl)-2-imidazolidinone and a phosphodiesterase inhibitor, were growth-inhibited by subnanogram concentrations of cholera toxin. Effects of toxin were detected by the absence of a yellow pH change (phenol red indicator) which normally accompanies the production of acid metabolites by lymphoma cells. An assay using S49 cells grown in microtiter plates, which is capable of detecting 10 pg of cholera toxin or 0.01 units of cholera antitoxin, was used in screening for nontoxinogenic mutants of Vibrio cholerae strain 569B. The properties of two mutants of the Tox--phenotype, which lacked biologically and immunologically detectable toxin products, are described.

Animals↗
PubMed1978

Agenesis of the corpus callosum: report of two pre-school children and review of the literature.

The results of neuropsychological examinations of two patients with agenesis of the corpus callosum showed low intelligence-test performance, impared visuo-motor co-ordination and impaired bimanual co-ordination. The most striking deficits were observed in Case A, particularly in her inability to identify objects verbally when placed in the non-dominant hand, and in her ability to complete a task with the non-dominant hand without vision, when she was unable to complete the same task with vision. This patient is unusual insofar as she manifests deficits noted in acallosal patients, as well as some noted in split-brain patients but not previously ascribed to acallosal patients.

Agenesis of Corpus Callosum↗
PubMed1978

Effects of methylprednisolone on hydrogen ion absorption in the canine stomach.

The effect of methylprednisolone (2 mg/kg per day given parenterally for 3 doses, 2 wk or 12 wk) on the permeability of mammalian gastric mucosa to hydrogen ion (H(+)) was examined with denervated fundic pouches in dogs with antrectomies. Transmucosal electric potential difference (PD) and net fluxes of H(+) and Na(+) were determined for luminal [H(+)] from 20 to 160 mM and [Na(+)] from 1 to 140 mM ([H(+)] and [Na(+)] were varied reciprocally). The PD was 50-60 mV lumen negative and was constant over the entire range of Na(+) and H(+) concentration tested. Net H(+) flux varied linearly with [H(+)]. Extrapolation indicated apparent H(+) loss at zero luminal concentration, suggesting a basal HCO(3) (-) secretion. Addition of acetylsalicylic acid (ASA) or taurocholate decreased the PD to 30-40 mV and increased threefold the slope of the relation between net H(+) flux and [H(+)] (k(H)). Calculation of PD-independent permeability constants for H(+) (P(H)) with the Goldman constant field equation indicated that this increase in k(H) could not be attributed solely to the associated decrease in PD. Prednisolone administered for 3 doses had no effect on either the basal mucosal permeability to H(+) or the altered permeability induced by ASA or taurocholate. Chronic administration induced a low rate of basal acid secretion (at 12 wk) but had no effect on either PD or k(H). However, the increase in k(H) and P(H) that developed upon addition of ASA or taurocholate in chronically treated dogs was more than one and a half times that of controls. These data suggest that prolonged treatment with glucocorticoids increases susceptibility of the gastric mucosa to damage by agents that increase permeability to H(+).

Absorption↗