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M Field

Publications and source records attributed to M Field.

At least 91 records · Page 5Linked to original sources
PubMed1984

Differing effects of cGMP and cAMP on ion transport across flounder intestine.

The intestinal epithelium of the winter flounder is highly cation selective and actively absorbs NaCl via a bumetanide-sensitive (Na + K + 2Cl) cotransport system; it also actively secretes K+. Combined addition of adenosine 3',5'-cyclic monophosphate (cAMP) and theophylline was previously shown to partially inhibit NaCl absorption and to increase passive Cl- permeability. Because theophylline increases cyclic GMP (cGMP) and cAMP concentrations, we compared the effects of the 8-Bromo analogues of these two nucleotides on ion transport. cGMP inhibits Cl- absorption, K+ secretion, and Cl- and K+ influx across the brush border as effectively as do furosemide and bumetanide. Even at maximal doses, cAMP is less effective than cGMP in inhibiting ion transport; however, unlike cGMP, it abolishes the cation selectivity of the epithelium by greatly increasing Cl- permeability. The effects of the two nucleotides are not additive with each other or with those of bumetanide, although cGMP or bumetanide can further inhibit transport in cAMP-treated tissues.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1984

Potassium transport by flounder intestinal mucosa.

We studied the mechanisms of K transport across an epithelium in which NaCl absorption is mediated primarily by Na/K/Cl cotransport at the apical membrane. Rubidium served as a reliable K substitute; under control conditions, both K and Rb were actively secreted. During secretion, K (Rb) enters across the basolateral membrane via the Na/K pump and exits across the apical membrane through K conductance pathways, since serosal ouabain or mucosal barium abolished K secretion, mucosal furosemide or Cl-free media blocked K secretion by interfering with access of Na to the pump, and elevated mucosal solution [K] or [Rb] depolarized the apical membrane electrical potential difference. Mucosal Ba unmasked active Rb absorption that could be blocked by mucosal furosemide. These findings illustrate active K absorption and secretion across an epithelium that comprises a single cell type in which opposing K fluxes across the apical membrane are mediated by Na/K/Cl cotransport entry and conductive K exit. The direction of transepithelial K transport is determined by the relative activities of these pathways.

Animals↗
PubMed1984

Placentophagy.

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Female↗
PubMed1984

An antiabsorptive basis for precipitated withdrawal diarrhea in morphine-dependent rats.

Diarrhea is a common manifestation of withdrawal from opiates in dependent subjects. This study examined the possibility that this diarrhea results in part from alterations in intestinal fluid transport. Isolated loops of jejunum, ileum and colon were created in morphine-dependent and nondependent rats implanted s.c. with morphine or lactose pellets, respectively. The administration of naltrexone (1 mg/kg s.c.) or its quaternary analog methylnaltrexone (0.01-3 mg/kg i.v.), which does not readily cross the blood-brain barrier, produced a dose-related reduction in fluid absorption from the jejunum and colon of dependent animals only. Similar effects were observed after the i.c.v. injection of quaternary naltrexone (1.0-10 microgram/rat). Both narcotic antagonists, given by any route, produced no change in ileal absorption. Pretreatment with hexamethonium (10 mg/kg i.v.) or atropine (4 mg/kg i.v.) attenuated the antiabsorptive effects of quaternary naltrexone on the jejunum. Serosal addition of naltrexone (10 microM) had no effect on Na or Cl fluxes, short-circuit current or tissue conductance across isolated segments of intestinal mucosa from dependent and nondependent rats. These results indicate that precipitated opiate withdrawal is associated with decreases in jejunal and colonic fluid absorption mediated at sites within both the central nervous system and periphery. Moreover, these effects are not a consequence of a direct opiate action on enterocytes.

Animals↗
PubMed1983

Isolation of transporting plasma membrane vesicles from bovine tracheal epithelium.

A method is described for isolating plasma membrane vesicles from bovine tracheal epithelium. The procedure yields highly purified apical membranes which are enriched 19-fold in the marker enzyme, alkaline phosphatase. Contamination of this fraction by other organelles is minimal. Basolateral membranes isolated from the same preparation have a 4-fold enrichment of (Na+ + K+)-ATPase and a 2-fold reduction in alkaline phosphatase specific activity compared to the starting material. Assays of Na+ uptake by the apical membrane vesicles demonstrate their suitability for transport studies. Transport of Na+ into an intravesicular space was demonstrated by (1) a linear inverse correlation between Na+ uptake and medium osmolarity; (2) complete release of accumulated Na+ by treatment with detergent; and (3) a marked temperature-dependence of Na+ uptake rate. Other features of Na+ transport were (1) inhibition by amiloride; (2) insensitivity to furosemide; and (3) anion-dependence of uptake rate with the following selectivity:SCN- greater than Cl- greater than gluconate-.

Alkaline Phosphatase↗
PubMed1983

Electrophysiology of Cl secretion in canine trachea.

Conventional microelectrode techniques were employed to determine the mechanism of Cl secretion by canine tracheal epithelium. Epinephrine, a potent stimulator of Cl secretion in these cells, hyperpolarized both the transepithelial potential (20 to 38.9 mV) and the potential across the basolateral membrane (-63.9 to -68.2 mV) and depolarized the potential across the apical membrane (-43.9 to -29.3 mV). Epinephrine also caused a decrease in the transepithelial resistance and ratio of apical to apical + basolateral membrane resistances (777 to 379 omega cm2 and 0.71 to 0.35, respectively) though the change in the latter was biphasic, first decreasing then slightly increasing. Ionic substitutions, either Na, K or Cl, in the mucosal bathing solutions were found to cause changes in the resistances and potentials measured. In the presence of epinephrine, the changes produced by the Na and K substitutions decreased, while those produced by altering the mucosal Cl concentration increased. A model was designed to analyze the results from these experiments. When used in conjunction with the Goldman-Hodgkin-Katz equation, the results from this model indicate that epinephrine caused a large increase in the Cl permeability of the apical membrane of the cell. From these results we conclude that the increase in Cl secretion caused by epinephrine is accompanied by at least two cellular events: the primary event is an increase in the Cl conductance of the apical membrane; the second event is either an increase in the conductance of the basolateral membrane (probably due to an increase in K permeability) or an increase in shunt conductance or a combination of both.

Animals↗
PubMed1983

Enterocyte alpha 2-adrenergic receptors: yohimbine and p-aminoclonidine binding relative to ion transport.

We previously reported that alpha 2-adrenergic agonists enhance absorption and inhibit secretion of electrolytes in small intestine. The present study was undertaken to characterize and localize the relevant receptors. Plasma membranes derived from isolated rabbit ileal epithelial cells were incubated with either [3H]yohimbine (Yo), an alpha 2-antagonist, or p-[3H]aminoclonidine (PAC), an alpha 2-agonist. Scatchard analysis of [3H]Yo binding suggests a single receptor. Competitive displacement of Yo from this receptor by other ligands had a potency order characteristic for alpha 2-receptors in other tissue systems. A Scatchard plot of [3H]PAC binding was curvilinear and best fit by assuming two independent site. Competitive displacement of [3H]PAC by PAC in the presence of 140 mM Na+ or 0.1 mM GTP increased the IC50 for PAC binding from 10 nM to 100 and 105 nM, respectively, and the Hill coefficient from 0.7 to 1.2 and 1.0, respectively. The ED50 for PAC effect on short-circuit current (200 nM) does not differ significantly from these values. We conclude that alpha 2-receptors are present on ileal enterocytes and that these receptors mediate enterocyte fluid and electrolyte transport function.

Animals↗
PubMed1983

Bradykinin-stimulated electrolyte secretion in rabbit and guinea pig intestine. Involvement of arachidonic acid metabolites.

Bradykinin (BK) increases short-circuit current (Isc) when added to the serosal side of rabbit or guinea pig ileum or rabbit colon. Significant effects on Isc are seen at concentrations as low as 10(-10) M. Anion substitution experiments and unidirectional 36Cl flux measurements indicate that this effect of BK on Isc is due to Cl secretion. The effect of BK on Isc can be partially blocked (60-70% inhibition) by cyclooxygenase inhibitors (indomethacin and/or naproxen) and completely blocked by the phospholipase inhibitor, mepacrine. The combined cyclooxygenase/lipoxygenase inhibitors BW 755 and eicosa-5,8,11,14-tetraynoic acid (ETYA) also completely block the effect of BK on Isc but the slow-reacting substance of anaphylaxis (SRS-A) antagonist FPL 55712 has no effect. None of the above inhibitors diminish the effect on Isc of other exogenously added secretory stimuli such as vasoactive intestinal peptide (VIP), theophylline, or prostaglandin E2 (PGE2). Prior desensitization of rabbit ileum to PGE2 blocks the effect on Isc of BK but not those of VIP or theophylline. Conversely, prior desensitization of rabbit ileum to BK greatly reduces the effect of PGE2 on Isc. BK also stimulates the synthesis of PGE2 in rabbit ileal and colonic mucosa and this effect can be blocked by prior addition of either indomethacin or mepacrine. These effects of BK are similar to those of exogenously added arachidonic acid (AA). AA also stimulates Cl secretion and increases PGE2 synthesis and its effect on Isc can be inhibited by prior desensitization to PGE2 or by prior addition of indomethacin. The above results indicate that BK stimulates active Cl secretion in both small and large intestine and suggest that this effect is due to the intracellular release of AA. Although the prostaglandins appear to be the major products of AA metabolism contributing to the secretory response, lipoxygenase products may also play a role.

Animals↗
PubMed1982

The cellular mechanism of active chloride secretion in vertebrate epithelia: studies in intestine and trachea.

The cellular mechanism of active chloride secretion, as it is manifested in the intestine and trachea, appears to possess the following elements: (1)NaCl cl-transport across the basolateral membrane; (2) Cl- accumulation in the cell above electrochemical equilibrium due to the Na+ gradient; (3) a basolateral Na+-K+ pump that maintains the Na+ gradient; (4) a hormone-regulated Cl- permeability in the apical membrane; (5) passive Na/ secretion through a paracellular route, driven by the transepithelial potential difference; and (6) an increase in basolateral membrane K+ permeability occurring in conjunction with an increase in Na+-K+ pump rate. Electrophysiological studies in canine trachea support this model. Adrenalin, a potent secretory stimulus in that tissue, increases apical membrane conductance through a selective increase in Cl- permeability. Adrenalin also appears to increase basolateral membrane K+ permeability. Whether or not adrenalin also increases paracellular Na+ permeability is unclear. Some of the testable implications of the above secretion model are discussed.

Animals↗
PubMed1982

Stimulation of colonic secretion by lipoxygenase metabolites of arachidonic acid.

Both 5-hydroperoxyeicosatetraenoic acid (5-HPETE) and 5-hydroxyeicosatetraenoic acid (5-HETE) increased the short-circuit current (Isc) in rabbit colonic mucosa mounted in vitro in Ussing chambers. Measurements of chlorine-36 fluxes indicated that the Isc response to 5-HPETE is due to stimulation of active chlorine secretion. 9-, 11-, and 12-HPETE's and leukotrienes C4 and B4 produced either very small increases in Isc or no increase. In contrast to results in rabbit colon, no HPETE, HETE, or leukotriene was effective in rabbit ileal mucosa. The effects of 5-HPETE in the rabbit colon were unaffected by mepacrine, but could be partially blocked by indomethacin. These results suggest that drugs which block both cyclooxygenase and lipoxygenase may be effective antidiarrheals in patients with colitis.

Animals↗
PubMed1982

alpha 2-Adrenergic receptor regulation of ion transport in rabbit ileum.

Catecholamines are known to decrease short-circuit current (Isc), stimulate NaCl absorption, and inhibit HCO3 secretion in rabbit ileal mucosa in vitro. These effects appear to be mediated by alpha-adrenergic receptors because they are partially blocked by phentolamine and not by propranolol. To further characterize this receptor system, we determined the interactions of epinephrine (Epi) with alpha-subtype-selective antagonists. Prazosin (PZ), a specific alpha 1-antagonist, did not alter the Epi dose-response curve at concentrations up to 10(-5) M. Yohimbine (YO), a specific alpha 2-antagonist, completely inhibited the Epi effect on Isc. At 10(-5) M, YO increased by 70-fold the concentration of Epi required to produce a half-maximal effect (ED50; from 1.4 X 10(-7) M to 10(-5) M). YO and PZ by themselves had no significant effect on Isc in concentrations up to 10(-5) M. Clonidine, a specific alpha 2-agonist, decreased Isc with an ED50 similar to that of Epi; its effect was blocked by YO but not by PZ. Two alpha 1-selective agonists, methoxamine and phenylephrine, only caused a decrease in Isc in doses greater than 10(-5) M. This effect was reversed by YO but not by PZ. The effects of YO and PZ on Epi-modified Cl fluxes were also determined. YO completely aborted the effects of Epi on net Cl flux. No significant effects were seen with PZ. We conclude that the effects of Epi on ileal ion transport are mediated by a specific alpha 2-adrenergic receptor present in ileal mucosa and that no physiologic alpha 1-receptor function can be demonstrated.

Animals↗
PubMed1982

cGMP modulation of ileal ion transport: in vitro effects of Escherichia coli heat-stable enterotoxin.

Diarrheagenic strains of Escherichia coli have been shown to produce a heat-stable enterotoxin (ST) that simulates guanylate cyclase, increases short-circuit current (Isc), and inhibits active Cl absorption in the intestine. In rabbit ileum, the ion transport effects are smaller than those produced by cAMP-related agonists. Because ST may be a selective cGMP agonist, we further explored its mode of action in rabbit ileum. ST inhibits net Na and net Cl absorption. ST also inhibits the same fraction of Cl influx across the brush border that theophylline inhibits. At maximal doses, ST and 8-bromo-cGMP (8-Br-cGMP) had nearly equal, nonadditive effects of Isc that were about 66% of that produced by 8-Br-cAMP. ST increased mucosal cGMP concentration 16-fold, whereas epinephrine, an inhibitor of secretion, increased cGMP concentration by only 30%. This is insufficient to alter ion transport because doses of ST that increased cGMP concentration by 100% failed to alter Cl fluxes. Furthermore, epinephrine did not increase cGMP concentration in isolated enterocytes. We conclude that 1) cGMP mediates ST effects on ion transport, and 2) although ST and cAMP-related agonists have the same antiabsorptive effects, ST is less effective in stimulating electrogenic Cl secretion.

Animals↗